Clark, Luke; Studer, Bettina; Bruss, Joel; Tranel, Daniel; Bechara, Antoine
Gambling is a naturalistic example of risky decision-making. During gambling, players typically display an array of cognitive biases that create a distorted expectancy of winning. This study investigated brain regions underpinning gambling-related cognitive distortions, contrasting patients with focal brain lesions to the ventromedial prefrontal cortex (vmPFC), insula, or amygdala ("target patients") against healthy comparison participants and lesion comparison patients (i.e., with lesions that spare the target regions). A slot machine task was used to deliver near-miss outcomes (i.e., nonwins that fall spatially close to a jackpot), and a roulette game was used to examine the gambler's fallacy (color decisions following outcome runs). Comparison groups displayed a heightened motivation to play following near misses (compared with full misses), and manifested a classic gambler's fallacy effect. Both effects were also observed in patients with vmPFC and amygdala damage, but were absent in patients with insula damage. Our findings indicate that the distorted cognitive processing of near-miss outcomes and event sequences may be ordinarily supported by the recruitment of the insula. Interventions to reduce insula reactivity could show promise in the treatment of disordered gambling.
Kalezić, Nevena; Dimitrijević, Ivan; Leposavić, Ljubica; Kocica, Mladen; Bumbasirević, Vesna; Vucetić, Cedomir; Paunović, Ivan; Slavković, Nemanja; Filimonović, Jelena
Cognitive dysfunctions are relatively common in postoperative and critically ill patients. This complication not only compromises recovery after surgery, but, if persistent, it minimizes and compromises surgery itself. Risk factors of postoperative cognitive disorders can be divided into age and comorbidity dependent, and those related to anesthesia and surgery. Cardiovascular, orthopedic and urologic surgery carries high risk of postoperative cognitive dysfunction. It can also occur in other types of surgical treatment, especially in elderly. Among risk factors of cognitive disorders, associated with comorbidity, underlying psychiatric and neurological disorders, substance abuse and conditions with elevation of intracranial pressure are in the first place in postoperative patients. Preoperative and perioperative predisposing conditions for cognitive dysfunction and their incidence were described in our paper. These are: geriatric patients, patients with substance abuse, preexisting psychiatric or cognitive disorders, neurologic disease with high intracranial pressure, cerebrovascular insufficiency, epilepsia, preeclampsia, acute intermittent porphyria, operation type, brain hypoxia, changes in blood glucose level, electrolyte imbalance, anesthetic agents, adjuvant medication and intraoperative awareness. For each of these factors, evaluation, prevention and treatment strategies were suggested, with special regard on anesthetic technique.
Hasselbalch, Bo Jacob; Knorr, Ulla Benedichte Søsted; Hasselbalch, Steen
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.......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....
Lund, H; Jønsson, A; Andresen, Jesper Graubæk
of the cognitive impairment seen in MS and constitute a supplement to traditional measurement of T2 lesion volume. Materials and Methods - Fifty patients with clinically definite MS were included (38 women, 12 men). Patients were MR scanned, neuropsychologically tested, and evaluated clinically with the Kurtzke......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...... 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...
Michael JL Sullivan
Full Text Available OBJECTIVES: To describe the pattern of perceived cognitive deficits in patients with whiplash injury, to examine the relation between perceived cognitive deficits and disability, and to examine the determinants of perceived cognitive deficits in patients with whiplash injury.
Milena V. Bonini
Full Text Available The assessment of aphasics’ cognitive performance is challenging and such patients are generally excluded from studies that describe cognitive deficits after stroke. We evaluated aphasics’ performance in cognitive tasks compared to non-aphasic subjects. A sample of 47 patients (21 aphasics, 17 non-aphasics with left hemisphere lesions and 9 non-aphasics with right hemisphere lesions performed cognitive tasks (attention, verbal and visual memory, executive functions, visuospatial skills and praxis. Aphasic patients performed poorer than all non-aphasics in Digit Span (p < 0.001, Clock-Drawing Test (p = 0.006, Verbal memory (p = 0.002, Visual Memory (p < 0.01, Verbal Fluency (p < 0.001, and Gesture Praxis (p < 0.001. Aphasia severity correlated with performance in Trail Making test part B (p = 0.004, Digit Span forward (p < 0.001 and backwards (p = 0.011, and Gesture Praxis (p = 0.002. Aphasia is accompanied by deficits not always easy to be evaluated by cognitive tests due to speech production and motor impairments. Assessment of cognitive functions in aphasics might contribute to optimize therapeutic intervention.
Ewa Małgorzata Szepietowska
Full Text Available Objective: The aim of the study was to determine whether the intensity of cognitive complaints can, in conjunction with other selected variables, predict the general level of cognitive functions evaluated with the Montreal Cognitive Assessment (MoCA test. Current reports do not show clear conclusions on this subject. Some data indicate that cognitive complaints have a predictive value for low scores in standardised tasks, suggesting cognitive dysfunction (e.g. mild cognitive impairment. Other data, however, do not support the predictive role of complaints, and show no relationship to exist between the complaints and the results of cognitive tests. Material and methods: The study included 118 adults (58 women and 60 men. We used the MoCA test, a self-report questionnaire assessing the intensity of cognitive complaints (Patient-Reported Outcomes in Cognitive Impairment – PROCOG and Dysexecutive Questionnaire/Self – DEX-S, and selected subtests of the Wechsler Adult Intelligence Scale-Revised (WAIS-R PL. On the basis of the results from the MoCA test, two separate groups were created, one comprising respondents with lower results, and one – those who obtained scores indicating a normal level of cognitive function. We compared these groups according to the severity of the complaints and the results obtained with the other methods. Logistic regression analysis was performed taking into account the independent variables (gender, age, result in PROCOG, DEX-S, and neurological condition and the dependent variable (dichotomized result in MoCA. Results: Groups with different levels of performance in MoCA differed in regards of some cognitive abilities and the severity of complaints related to semantic memory, anxiety associated with a sense of deficit and loss of skills, but provided similar self-assessments regarding the efficiency of episodic memory, long-term memory, social skills and executive functions. The severity of complaints does not allow
Laura L. Fazakas-DeHoog
Full Text Available Although cognitive distortions and deficits are known risk factors for the development and escalation of suicide ideation and behaviour, no empirical work has examined how these variables interact to predict suicide ideation. The current study proposes an integrative model of cognitive distortions (hopelessness and negative evaluations of self and future and deficits (problem solving deficits, problem solving avoidance, and cognitive rigidity. To test the integrity of this model, a sample of 397 undergraduate students completed measures of deficits, distortions, and current suicide ideation. A structural equation model demonstrated excellent fit, and findings indicated that only distortions have a direct effect on suicidal thinking, whereas cognitive deficits may exert their effects on suicide ideation via their reciprocal relation with distortions. Findings underscore the importance of both cognitive distortions and deficits for understanding suicidality, which may have implications for preventative efforts and treatment.
Full Text Available The article is devoted to the search for more accurate psycho-diagnostic methods and assessment tools for determining the degree of cognitive deficits in patients with schizophrenic disorders. The concepts of "cognitive deficits" and "cognitive profile", understood as the ratio of intact and damaged components of cognitive processes and their schematic representation are discussed. The authors substantiate the need for a clear gradation of cognitive impairments in schizophrenia, development of universal translation algorithms of traditional qualitative results (meaningful analysis of violations of cognitive activity in quantitative indicators. The article is based on the results of experimental psychological study. The investigation involved 128 patients: 76 people with Paranoid schizophrenia (F20 according to ICD-10 and 52 persons with Schizotypal disorder (F21 according to ICD-10. To assess the cognitive deficit, both traditional domestic methods and foreign tests, rarely used in the practice of a medical psychologist were conducted. The study analyzed the difference in cognitive tests performance between groups of patients with several types of schizophrenia and with different disease duration (up to 5 years and more. On the basis of quantitative data, a "cognitive profile" was lined for each disease. As a result, different variants of cognitive deficits, depending on the shape and course of the disease have been identified. The structure and dynamics of the cognitive deficits associated with schizophrenia and various forms depending on the different duration of the disease is described in detail. Also cognitive profiles compiled on this basis.
Bose, Anushree; Agarwal, Sri Mahavir; Kalmady, Sunil V; Venkatasubramanian, Ganesan
Hippocampal deficits are an established feature of schizophrenia and are complementary with recent evidences of marked allocentric processing deficits being reported in this disorder. By "Cognitive mapping" we intend to refer to the concepts from the seminal works of O'Keefe and Nadel (1978) that led to the development of cognitive map theory of hippocampal function. In this review, we summarize emerging evidences and issues that indicate that "Cognitive mapping deficits" form one of the important cognitive aberrations in schizophrenia. The importance has been placed upon hippocampally mediated allocentric processing deficits and their role in pathology of schizophrenia, for spatial/representational cognitive deficits and positive symptoms in particular. It is modestly summarized that emerging evidences point toward a web of spatial and cognitive representation errors concurrent with pronounced hippocampal dysfunction. In general, it can be stated that there are clear and consistent evidences that favor the cognitive mapping theory in explaining certain deficits of schizophrenia and for drawing out a possible and promising endophenotype/biomarkers. Further research in this regard demands attention.
Englund, Julia A.; Decker, Scott L.; Allen, Ryan A.; Roberts, Alycia M.
Cognitive deficits in working memory (WM) are characteristic features of Attention-Deficit/Hyperactivity Disorder (ADHD) and autism. However, few studies have investigated cognitive deficits using a wide range of cognitive measures. We compared children with ADHD ("n" = 49) and autism ("n" = 33) with a demographically matched…
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-episode schizop...... are comparable to the implicit and explicit mentalising discussed in the developmental literature. The two forms of social cognitive deficits are likely to require quite different social cognitive interventions.......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...
Särkämö, Teppo; Tervaniemi, Mari; Soinila, Seppo; Autti, Taina; Silvennoinen, Heli M; Laine, Matti; Hietanen, Marja
We studied the relationship between musical and cognitive deficits by testing middle cerebral arterial (MCA) stroke patients (n= 53) with a shortened version of the Montreal Battery of Evaluation of Amusia (MBEA) and an extensive neuropsychological test battery. Results showed that amusic patients (n= 32) had more severe cognitive deficits, especially in working memory and executive functioning, than did non-amusic patients (n= 21), and the severity of amusia also correlated with attention deficits. These findings thus suggest that domain-general attention, executive, and working memory processes are associated with amusia after stroke.
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...
Bast, Tobias; Pezze, Marie; McGarrity, Stephanie
We review recent evidence concerning the significance of inhibitory GABA transmission and of neural disinhibition, that is, deficient GABA transmission, within the prefrontal cortex and the hippocampus, for clinically relevant cognitive functions. Both regions support important cognitive functions, including attention and memory, and their dysfunction has been implicated in cognitive deficits characterizing neuropsychiatric disorders. GABAergic inhibition shapes cortico-hippocampal neural activity, and, recently, prefrontal and hippocampal neural disinhibition has emerged as a pathophysiological feature of major neuropsychiatric disorders, especially schizophrenia and age-related cognitive decline. Regional neural disinhibition, disrupting spatio-temporal control of neural activity and causing aberrant drive of projections, may disrupt processing within the disinhibited region and efferent regions. Recent studies in rats showed that prefrontal and hippocampal neural disinhibition (by local GABA antagonist microinfusion) dysregulates burst firing, which has been associated with important aspects of neural information processing. Using translational tests of clinically relevant cognitive functions, these studies showed that prefrontal and hippocampal neural disinhibition disrupts regional cognitive functions (including prefrontal attention and hippocampal memory function). Moreover, hippocampal neural disinhibition disrupted attentional performance, which does not require the hippocampus but requires prefrontal-striatal circuits modulated by the hippocampus. However, some prefrontal and hippocampal functions (including inhibitory response control) are spared by regional disinhibition. We consider conceptual implications of these findings, regarding the distinct relationships of distinct cognitive functions to prefrontal and hippocampal GABA tone and neural activity. Moreover, the findings support the proposition that prefrontal and hippocampal neural disinhibition
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. PsycINFO Database Record (c) 2012 APA, all rights reserved.
Loetscher, Tobias; Lincoln, Nadina B
Many survivors of stroke complain about attentional impairments, such as diminished concentration and mental slowness. However, the effectiveness of cognitive rehabilitation for improving these impairments is uncertain. To determine whether (1) people receiving attentional treatment show better outcomes in their attentional functions than those given no treatment or treatment as usual, and (2) people receiving attentional treatment techniques have a better functional recovery, in terms of independence in activities of daily living, mood and quality of life, than those given no treatment or treatment as usual. We searched the Cochrane Stroke Group Trials Register (October 2012), Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library October 2012), MEDLINE (1948 to October 2012), EMBASE (1947 to October 2012), CINAHL (1981 to October 2012), PsycINFO (1806 to October 2012), PsycBITE and REHABDATA (searched October 2012) and ongoing trials registers. We screened reference lists and tracked citations using Scopus. We included randomised controlled trials (RCTs) of cognitive rehabilitation for impairments of attention for people with stroke. The primary outcome was measures of global attentional functions, and secondary outcomes were measures of attention domains, functional abilities, mood and quality of life. Two review authors independently selected trials, extracted data and assessed trial quality. We included six RCTs with 223 participants. All six RCTs compared cognitive rehabilitation with a usual care control. Meta-analyses demonstrated no statistically significant effect of cognitive rehabilitation for persisting effects on global measures of attention (two studies, 99 participants; standardised mean difference (SMD) 0.16, 95% confidence interval (CI) -0.23 to 0.56; P value = 0.41), standardised attention assessments (two studies, 99 participants; P value ≥ 0.08) or functional outcomes (two studies, 99 participants; P value ≥ 0
Fervaha, Gagan; Zakzanis, Konstantine K; Foussias, George; Graff-Guerrero, Ariel; Agid, Ofer; Remington, Gary
Motivational and cognitive deficits are core features of schizophrenia, both closely linked with functional outcomes. Although poor effort and decreased motivation are known to affect performance on cognitive tests, the extent of this relationship is unclear in patients with schizophrenia. To evaluate the association between intrinsic motivation and cognitive test performance in patients with schizophrenia. Cross-sectional and 6-month prospective follow-up study performed at 57 sites in the United States, including academic and community medical treatment centers, participating in the Clinical Antipsychotic Trials of Intervention Effectiveness study. The primary sample included 431 stable patients with a DSM-IV diagnosis of schizophrenia currently receiving a stable medication regimen. Cognitive performance and intrinsic motivation were evaluated using a comprehensive neuropsychological test battery and a derived measure from the Heinrichs-Carpenter Quality of Life Scale, respectively. Symptom severity and functional status were also assessed. The primary outcome variable was global neurocognition. Individual domains of cognition were also evaluated for their association with motivation. Level of intrinsic motivation was significantly and positively correlated with global cognitive test performance, a relationship that held for each domain of cognition evaluated (correlation range, 0.20-0.34; P motivation and cognitive performance also remained significant after controlling for antipsychotic dose (P motivation during the 6-month follow-up was also found to be significantly related to improvement in global cognitive performance (P motivation and cognitive performance and suggest that test performance is not purely a measure of ability. Future studies assessing cognition in patients with schizophrenia should consider potential moderating variables such as effort and motivation. Implications for the assessment and interpretation of cognitive impairment based on
Full Text Available Humans are substantially a social species. Effective mental treatment cannot be obtained without addressing social behavior. Social cognition refers to the mental processes underlying social interactions, which allow individuals to make sense of the other peoples' behavior, to decipher emotions on their faces, and to draw conclusions about their intentions. The core domains of this multifaceted concept are theory of mind, social cue perception, attributional style and emotion perception/ processing. The amygdala, orbital frontal cortex and temporal cortex areas are typically activated during the processing of information within social-emotional context. The aforementioned brain areas are recognized as the major components of the so-called 'social brain'- specialized for the social interactions in humans. Adequate perceiving and processing of the social information is essential for an effective social functioning, which becomes obvious when it goes awry. Various psychiatric disorders are characterized by social cognitive deficits, among which schizophrenias, depression-anxiety and autism spectrum disorders were most broadly studied to date. Growing evidence suggest that these deficits underlie poor functional outcomes in patients with mental health impairments and have an important role in the initiation and maintenance of the disorders' symptoms. One of the most important goals of social neuroscience research is to provide a treatment intervention that will improve patients' social cognitive skills and the functional outcome. All together, the present review aims to provide a contemporary overview of the concept of social cognition, to outline its relation to psychopathology, and to discuss the implications for clinical practice and treatment.
Boukrina, Olga; Barrett, A M; Alexander, Edward J; Yao, Bing; Graves, William W
According to cognitive models of reading, words are processed by interacting orthographic (spelling), phonological (sound), and semantic (meaning) information. Despite extensive study of the neural basis of reading in healthy participants, little group data exist on patients with reading deficits from focal brain damage pointing to critical neural systems for reading. Here, we report on one such study. We have performed neuropsychological testing and magnetic resonance imaging on 11 patients with left-hemisphere stroke (picture or word choices to a target based on meaning), phonology (matching word choices to a target based on rhyming), and orthography (a two-alternative forced choice of the most plausible non-word). They also read aloud pseudowords and words with high or low levels of usage frequency, imageability, and spelling-sound consistency. As predicted by the cognitive model, when averaged across patients, the influence of semantics was most salient for low-frequency, low-consistency words, when phonological decoding is especially difficult. Qualitative subtraction analyses revealed lesion sites specific to phonological processing. These areas were consistent with those shown previously to activate for phonology in healthy participants, including supramarginal, posterior superior temporal, middle temporal, inferior frontal gyri, and underlying white matter. Notable divergence between this analysis and previous functional imaging is the association of lesions in the mid-fusiform gyrus and anterior temporal lobe with phonological reading deficits. This study represents progress toward identifying brain lesion-deficit relationships in the cognitive components of reading. Such correspondences are expected to help not only better understand the neural mechanisms of reading, but may also help tailor reading therapy to individual neurocognitive deficit profiles.
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...
Setti, Sharay E; Littlefield, Alyssa M; Johnson, Samantha W; Kohman, Rachel A
Activation of the immune system can impair cognitive function, particularly on hippocampus dependent tasks. Several factors such as normal aging and prenatal experiences can modify the severity of these cognitive deficits. One additional factor that may modulate the behavioral response to immune activation is obesity. Prior work has shown that obesity alters the activity of the immune system. Whether diet-induced obesity (DIO) influences the cognitive deficits associated with inflammation is currently unknown. The present study explored whether DIO alters the behavioral response to the bacterial endotoxin, lipopolysaccharide (LPS). Female C57BL/6J mice were fed a high-fat (60% fat) or control diet (10% fat) for a total of five months. After consuming their respective diets for four months, mice received an LPS or saline injection and were assessed for alterations in spatial learning. One month later, mice received a second injection of LPS or saline and tissue samples were collected to assess the inflammatory response within the periphery and central nervous system. Results showed that LPS administration impaired spatial learning in the control diet mice, but had no effect in DIO mice. This lack of a cognitive deficit in the DIO female mice is likely due to a blunted inflammatory response within the brain. While cytokine production within the periphery (i.e., plasma, adipose, and spleen) was similar between the DIO and control mice, the DIO mice failed to show an increase in IL-6 and CD74 in the brain following LPS administration. Collectively, these data indicate that DIO can reduce aspects of the neuroinflammatory response as well as blunt the behavioral reaction to an immune challenge. Copyright © 2014 Elsevier Inc. All rights reserved.
Tiemensma, Jitske; Andela, Cornelie D; Biermasz, Nienke R; Romijn, Johannes A; Pereira, Alberto M
The brain is a major target organ for cortisol considering its high density of glucocorticoid receptors. Several states of hypothalamus-pituitary-adrenal dysregulation point towards impairments in cognitive functioning. However, there is a very limited body of research on the effects of hypocortisolism on cognitive functioning. To evaluate cognitive functioning in patients with hypocortisolism (i.e., primary adrenal insufficiency (PAI)) and to examine the possible effect of postponing early-morning hydrocortisone intake on cognitive functioning. Thirty-one patients with PAI on regular morning hydrocortisone intake and 31 healthy matched controls underwent nine neuropsychological tests, evaluating memory and executive functioning. In addition, the effect of normal timing and postponement of morning hydrocortisone intake on neuropsychological tests were assessed in an additional 29 patients with PAI. Compared to controls, patients with PAI performed worse on auditory and visual memory tasks (all P ≤ 0.024) and executive functioning tasks (all P ≤ 0.012). In contrast, patients performed better on a concentration and an attention task (both Paffect the outcomes of neuropsychological tests. Patients on long-term hydrocortisone replacement for PAI show mild cognitive deficits compared to controls. There was no effect of postponement of regular hydrocortisone intake on cognition. Copyright © 2015 Elsevier Ltd. All rights reserved.
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 cognitive deficits found to be vocationally important will be examined. Upon examination of the extant literature, attention, executive function and verbal memory are areas of consistent impairment in remitted MDD patients. Cognitive domains shown to have considerable impact on vocational functioning include deficits in memory, attention, learning and executive function. Factors that adversely affect cognitive function related to occupational accommodation include higher age, late age at onset, residual depressive symptoms, history of melancholic/psychotic depression, and physical/psychiatric comorbidity, whereas higher levels of education showed a protective effect against cognitive deficit. Cognitive deficits are a principal mediator of occupational impairment in remitted MDD patients. Therapeutic interventions specifically targeting cognitive deficits in MDD are needed, even in the remitted state, to improve functional recovery, especially in patients who have a higher risk of cognitive deficit. PMID:26792035
Sloan, Rebecca S; Pressler, Susan J
Patients with chronic heart failure (HF) have impairment in memory, psychomotor speed, and executive function. The aim of this study was to describe how individuals with HF and cognitive deficits manage self-care in their daily lives. Using an interpretive phenomenology method, HF patients completed unstructured face-to-face interviews about their ability to manage complex health regimens and maintain their health-related quality of life. Analysis of data was aided by use of Atlas.ti computer software. The sample consisted of 12 patients (10 men; aged 43-81 years) who had previously undergone neuropsychological testing and were found to have deficits in 3 or more cognitive domains. Patients confirmed that they followed the advice of healthcare providers by adherence to medication regimens, dietary sodium restrictions, and HF self-care. One overarching theme was identified: "Re-cognition of Vulnerability: A Strange New World." This theme was further differentiated into 3 components: (1) not recognizing cognitive deficits; (2) recognizing cognitive deficits, described as (a) never could remember anything, (b) just old age, (c) HF-related change, and (d) making normal accommodations; and (3) recognizing vulnerability, explained by perception of (a) cognitive, (b) physical, and (c) social vulnerabilities, as well as perception of (d) the nearness of death. Although the study was designed to focus on the cognitive changes in HF patients, it was difficult to separate cognitive, physical, and social challenges. These changes are most useful when taken as a constellation. Healthcare professionals can use the knowledge to identify problems and interventions for HF patients.
Lima, Isabela M M; Peckham, Andrew D; Johnson, Sheri L
Prominent cognitive deficits have been documented in bipolar disorder, and multiple studies suggest that these deficits can be observed among non-affected first-degree relatives of those with bipolar disorder. Although there is variability in the degree of cognitive deficits, these deficits are robustly relevant for functional outcomes. A separate literature documents clear difficulties in emotionality, emotion regulation, and emotion-relevant impulsivity within bipolar disorder, and demonstrates that these emotion-relevant variables are also central to outcome. Although cognitive and emotion domains are typically studied independently, basic research and emergent findings in bipolar disorder suggest that there are important ties between cognitive deficits and the emotion disturbances observed in bipolar disorder. Understanding these relationships has relevance for fostering more integrative research, for clarifying relevant aspects related to functionality and vulnerability within bipolar disorder, and for the development of novel treatment interventions. Bipolar disorder (BD) is a severe psychiatric illness that has been ranked as one of the 20 leading medical causes of disability (WHO, 2011). BD has been shown to be the psychiatric disorder with the highest rates of completed suicide across two major cohort studies (Ilgen et al., 2010; Nordentoft, Mortensen, & Pedersen, 2011). In a cross-national representative sample, one in four persons diagnosed with bipolar I disorder reported a suicide attempt (Merikangas et al., 2011). Rates of relapse remain high despite available treatments (Gitlin, Swendsen, Heller, & Hammen, 1995), and in the year after hospitalization for manic episode, two-thirds of patients do not return to work (Strakowski et al., 1998). Poverty, homelessness, and incarceration are all too common (Copeland et al., 2009). Despite the often poor outcomes, there is also evidence for outstanding accomplishments and creativity among those with milder
Li, Xin; Ma, Chao; Zhang, Junying; Chen, Yaojing; Zhang, Zhanjun; Sun, Xuan; Chen, Kewei
Hypertension is considered a risk factor of cognitive impairments and could result in white matter changes. Current studies on hypertension-related white matter (WM) changes focus only on regional changes, and the information about global changes in WM structure network is limited. We assessed the cognitive function in 39 hypertensive patients and 37 healthy controls with a battery of neuropsychological tests. The WM structural networks were constructed by utilizing diffusion tensor tractography and calculated topological properties of the networks using a graph theoretical method. The direct and indirect correlations among cognitive impairments, brain WM network disruptions and hypertension were analyzed with structural equation modelling (SEM). Hypertensive patients showed deficits in executive function, memory and attention compared with controls. An aberrant connectivity of WM networks was found in the hypertensive patients (P Eglob = 0.005, P Lp = 0.005), especially in the frontal and parietal regions. Importantly, SEM analysis showed that the decline of executive function resulted from aberrant WM networks in hypertensive patients (p = 0.3788, CFI = 0.99). These results suggest that the cognitive decline in hypertensive patients was due to frontal and parietal WM disconnections. Our findings highlight the importance of brain protection in hypertension patients. (orig.)
Full Text Available Objectives : The aim of study was to evaluate the effect of Herbal medicine on post stroke cognitive deficit. Methods : All groups were treated with acupunture treatment, moxa treatment, herbal medicines, physical and occupational therapy for 4 weeks, additionally cardiotonic pills(CP were taken in the cardiotonic pills group. The effect of treatment was assessed using Verval fluency, MMSE-KC, Word List Immediate Recall test. Statistical significance was achived if the probability was less than 5%(p,0.05. Results : Verval fluency, MMSE-KC, Word List Immediate Recall test scores increased in both group. MMSEKC, Word List Immediate Recall test scores were significantly increased in the CP group. Verval fluency, MMSE-KC, Word List Immediate Recall test scores were significantly increased in the control group. In the Verval fluency, MMSE-KC, Word List Immediate Recall test of the CP group more increased compared to the control group. There were no significant differences between two groups. In the CP group, the scores of the infarction group more increased compared to the hemorrhage group. Conclusions : According to the these results, herbal medicines are effective to improve post stroke cognitive-deficit. Futher studies are needed to know cardiotonic pills in the ischemic stroke.
Frank, Jennifer Sandson; Vance, David E; Triebel, Kristen L; Meneses, Karen M
Adjuvant treatments, specifically chemotherapy and hormonal therapy, have dramatically increased breast cancer survival, resulting in increased attention to the residual effects of treatment. Breast cancer survivors (BCS) frequently report that cognitive deficits are a particular source of distress, interfering with many aspects of quality of life. The literature on neuropsychological performance measures in BCS supports the reality of subtle cognitive deficits after both chemotherapy and hormonal therapy. This premise is supported by recent imaging studies, which reveal anatomical changes after chemotherapy as well as changes in patterns of neural activation while performing cognitive tasks. This review suggests that, even when performance on neuropsychological performance measures is within normal limits, BCS may be using increased cognitive resources in the face of reduced cognitive reserve. Potential interventions for cognitive deficits after adjuvant therapy include prescriptions for healthy living, pharmacotherapy, complementary therapy, and cognitive remediation therapy directed toward specific cognitive deficits or a combination of several strategies.
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…
Bikic, Aida; Leckman, J. F.; Lindschou, Jane
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...... 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...
Giocondo, Flora; Curcio, Giuseppe
The primary aim of this contribution is to provide a critical discussion on cognitive and sociocognitive implications of spinocerebellar ataxias (SCAs) subtypes. The term SCA refers to a group of neurodegenerative disorders that have been increasingly investigated in the last years, sharing the characteristic of progressive ataxia resulting from degeneration of cerebellum and its connections. In past decades only involvement of cerebellum in behaviour and timing has been investigated, bringing to the belief about its central role in timing of movement and sensation, particularly for short intervals of time. Only very recently the cerebellum has been considered as a potentially important centre for cognitive processing and related spheres of social cognition, so that several studies with SCA patients have been carried out on these topics: as a consequence a section of this review will be dedicated to this important aspect. After a brief discussion on most commonly used methods to assess cognitive and socio-cognitive abilities in SCAs, cognitive and socio-cognitive profiles of principal SCA subtypes have been thoroughly reviewed and critically discussed. Due to the very poor literature in this field the most common SCA variants have been fully included (i.e. SCA1, SCA2, SCA3, SCA6 and SCA7). A comparative summary of the main characteristics of cognitive and social cognition deficit in SCA subtypes has been proposed together with a research agenda for future investigation in this field principally aimed at using measures of cognition and/or social cognition as potential predictors of the extent and progression of disease.
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…
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
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
Assis, Melissa S; Soares, Aluízio C; de Sousa, Dircilei N; Eudes-Filho, João; Faro, Lilian Rosana F; Carneiro, Fabiana P; da Silva, Mônica V; Motoyama, Andrea B; de Souza, Greice Maria R; Marchiori, Stéphanie; de Lima, Nadyelle T; Boëchat-Barros, Raphael; Ferreira, Vania M
There are many studies that have sought to find drug therapies to prevent harm arising from sepsis. Such studies have represented a progress in the support to septic patients and also in the development of new pharmacological alternatives. Our interest was to investigate the caffeine effect on sepsis behavioural and memory impairments. Male rats were anaesthetized and the surgery was made to allow exposure of the cecum, which was then squeezed to extrude a small amount of faeces from the perforation site, which was later placed back into the peritoneal cavity. This procedure, which served to generate experimental sepsis, is herein referred to as ceccum ligation and perforation (CLP). The caffeine (10 mg/kg) was administered by gavage route, once daily, during 7 or 14 consecutive days to investigate the effects of acute or subchronic caffeine treatment on long-term behavioural and cognitive deficits induced by CLP. On the last day, one hour after caffeine administration, the animals were submitted to open-field, elevated plus-maze (EPM), forced swimming, and step-down inhibitory avoidance tests. The results showed that caffeine increased the percentage of open arm entries and open arm time in the EPM test, and reduced the immobility time when compared to the sham-operated group. The caffeine also increased the latency in the inhibitory avoidance test platform. Our results demonstrated that the caffeine improved behavioural changes and improved the neurocognitive deficits of sepsis-surviving animals. It is possible that blockage of the adenosine receptors may be responsible for the results here observed. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
Zamarian, Laura; Högl, Birgit; Delazer, Margarete; Hingerl, Katharina; Gabelia, David; Mitterling, Thomas; Brandauer, Elisabeth; Frauscher, Birgit
Patients with narcolepsy often complain about attention deficits in everyday situations. In comparison with these subjective complaints, deficits in objective testing are subtler. The present study assessed the relationships between subjective complaints, objectively measured cognitive performance, disease-related variables, and mood. A total of 51 patients with narcolepsy and 35 healthy controls responded to questionnaires regarding subjectively perceived attention deficits, sleepiness, anxiety and depression. Moreover, they performed an extensive neuropsychological assessment tapping into attention, executive functions, and memory. Patients rated their level of attention in everyday situations to be relatively poor. In an objective assessment of cognitive functioning, they showed only slight attention and executive function deficits. The subjective ratings of attention deficits significantly correlated with ratings of momentary sleepiness, anxiety, and depression, but not with objectively measured cognitive performance. Momentary sleepiness and depression predicted almost 39% of the variance in the ratings of subjectively perceived attention deficits. The present study showed that sleepiness and depression, more than objective cognitive deficits, might play a role in the subjectively perceived attention deficits of patients with narcolepsy. The results suggested that when counselling and treating patients with narcolepsy, clinicians should pay attention to potential depression because subjective cognitive complaints may not relate to objective cognitive impairments. Copyright © 2014 Elsevier B.V. All rights reserved.
George Kwok Chu Wong
Full Text Available Cognitive deficits are common after aneurysmal subarachnoid haemorrhage (aSAH, and clinical evaluation is important for their management. Our hypothesis was that the Montreal Cognitive Assessment (MoCa is superior to the Mini-Mental State Examination (MMSE in screening for cognitive domain deficit in aSAH patients.We carried out a prospective observational and diagnostic accuracy study on Hong Kong aSAH patients aged 21 to 75 years who had been admitted within 96 hours of ictus. The domain-specific neuropsychological assessment battery, the MoCA and MMSE were administered 2-4 weeks and 1 year after ictus. A cognitive domain deficit was defined as a cognitive domain z score <-1.65 (below the fifth percentile. Cognitive impairment was defined as two or more cognitive domain deficits. The study is registered at ClinicalTrials.gov of the US National Institutes of Health (NCT01038193.Both the MoCA and the MMSE were successful in differentiating between patients with and without cognitive domain deficits and cognitive impairment at both assessment periods. At 1 year post-ictus, the MoCA produced higher area under the curve scores for cognitive impairment than the MMSE (MoCA, 0.92; 95% CI, 0.83 to 0.97 versus MMSE, 0.77; 95% CI, 0.66 to 0.83, p = 0.009.Cognitive domain deficits and cognitive impairment in patients with aSAH can be screened with the MoCA in both the subacute and chronic phases.
Tripathi, Adarsh; Shukla, Rashmi
Cognitive deficits are one of the core symptoms of schizophrenia that evolve during the course of schizophrenia, after being originated even before the onset of illness. Existing pharmacological and biological treatment modalities fall short to meet the needs to improve the cognitive symptoms; hence, various cognitive remediation strategies have been adopted to address these deficits. Research evidences suggest that cognitive remediation measures improve the functioning, limit disability bettering the quality of life. The functional outcomes of cognitive remediation in schizophrenia are resultant of neurobiological changes in specific brain areas. Recent years witnessed significant innovations in cognitive remediation strategies in schizophrenia. This comprehensive review highlights the biological correlates of cognitive deficits in schizophrenia and the remedial measures with evidence base. PMID:29397662
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.
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…
Full Text Available The perception of music can be impaired after a stroke. This dysfunction is called amusia and amusia patients often also show deficits in visual abilities, language, memory, learning, and attention. The current study investigated whether deficits in music perception are selective for musical input or generalize to other perceptual abilities. Additionally, we tested the hypothesis that deficits in working memory or attention account for impairments in music perception. Twenty stroke patients with small infarctions in the supply area of the middle cerebral artery were investigated with tests for music and visual perception, categorization, neglect, working memory and attention. Two amusia patients with selective deficits in music perception and pronounced lesions were identified. Working memory and attention deficits were highly correlated across the patient group but no correlation with musical abilities was obtained. Lesion analysis revealed that lesions in small areas of the putamen and globus pallidus were connected to a rhythm perception deficit. We conclude that neither a general perceptual deficit nor a minor domain general deficit can account for impairments in the music perception task. But we find support for the modular organization of the music perception network with brain areas specialized for musical functions as musical deficits were not correlated to any other impairment.
Rosemann, Stephanie; Brunner, Freimuth; Kastrup, Andreas; Fahle, Manfred
The perception of music can be impaired after a stroke. This dysfunction is called amusia and amusia patients often also show deficits in visual abilities, language, memory, learning, and attention. The current study investigated whether deficits in music perception are selective for musical input or generalize to other perceptual abilities. Additionally, we tested the hypothesis that deficits in working memory or attention account for impairments in music perception. Twenty stroke patients with small infarctions in the supply area of the middle cerebral artery were investigated with tests for music and visual perception, categorization, neglect, working memory and attention. Two amusia patients with selective deficits in music perception and pronounced lesions were identified. Working memory and attention deficits were highly correlated across the patient group but no correlation with musical abilities was obtained. Lesion analysis revealed that lesions in small areas of the putamen and globus pallidus were connected to a rhythm perception deficit. We conclude that neither a general perceptual deficit nor a minor domain general deficit can account for impairments in the music perception task. But we find support for the modular organization of the music perception network with brain areas specialized for musical functions as musical deficits were not correlated to any other impairment.
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.
Polcher, Alexandra; Frommann, Ingo; Koppara, Alexander; Wolfsgruber, Steffen; Jessen, Frank; Wagner, Michael
There is a need for more sensitive neuropsychological tests to detect subtle cognitive deficits emerging in the preclinical stage of Alzheimer's disease (AD). Associative memory is a cognitive function supported by the hippocampus and affected early in the process of AD. We developed a short computerized face-name associative recognition test (FNART) and tested whether it would detect memory impairment in memory clinic patients with mild cognitive impairment (MCI) and subjective cognitive decline (SCD). We recruited 61 elderly patients with either SCD (n = 32) or MCI (n = 29) and 28 healthy controls (HC) and compared performance on FNART, self-reported cognitive deterioration in different domains (ECog-39), and, in a reduced sample (n = 46), performance on the visual Paired Associates Learning of the CANTAB battery. A significant effect of group on FNART test performance in the total sample was found (p < 0.001). Planned contrasts indicated a significantly lower associative memory performance in the SCD (p = 0.001, d = 0.82) and MCI group (p < 0.001, d = 1.54), as compared to HCs, respectively. The CANTAB-PAL discriminated only between HC and MCI, possibly because of reduced statistical power. Adjusted for depression, performance on FNART was significantly related to ECog-39 Memory in SCD patients (p = 0.024) but not in MCI patients. Associative memory is substantially impaired in memory clinic patients with SCD and correlates specifically with memory complaints at this putative preclinical stage of AD. Further studies will need to examine the predictive validity of the FNART in SCD patients with regard to longitudinal (i.e., conversion to MCI/AD) and biomarker outcomes.
O'Reilly, Kally C; Perica, Maria I; Fenton, André A
Cognitive impairments are amongst the most debilitating deficits of schizophrenia and the best predictor of functional outcome. Schizophrenia is hypothesized to have a neurodevelopmental origin, making animal models of neurodevelopmental insult important for testing predictions that early insults will impair cognitive function. Rats exposed to methylazoxymethanol acetate (MAM) at gestational day 17 display morphological, physiological and behavioral abnormalities relevant to schizophrenia. Here we investigate the cognitive abilities of adult MAM rats. We examined brain activity in MAM rats by histochemically assessing cytochrome oxidase enzyme activity, a metabolic marker of neuronal activity. To assess cognition, we used a hippocampus-dependent two-frame active place avoidance paradigm to examine learning and spatial memory, as well as cognitive control and flexibility using the same environment and evaluating the same set of behaviors. We confirmed that adult MAM rats have altered hippocampal morphology and brain function, and that they are hyperactive in an open field. The latter likely indicates MAM rats have a sensorimotor gating deficit that is common to many animal models used for schizophrenia research. On first inspection, cognitive control seems impaired in MAM rats, indicated by more errors during the two-frame active place avoidance task. Because MAM rats are hyperactive throughout place avoidance training, we considered the possibility that the hyperlocomotion may account for the apparent cognitive deficits. These deficits were reduced on the basis of measures of cognitive performance that account for motor activity differences. However, though other aspects of memory are intact, the ability of MAM rats to express trial-to-trial memory is delayed compared to control rats. These findings suggest that spatial learning and cognitive abilities are largely intact, that the most prominent cognitive deficit is specific to acquiring memory in the MAM
Full Text Available Neuropsychological assessments of cognitive dysfunction in cerebrovascular illness commonly target basic cognitive functions involving aspects of memory, attention, language, praxis, and number processing. Here, I highlight the clinical importance of often-neglected social cognition functions. These functions recruit a widely distributed neural network, making them vulnerable in most cerebrovascular diseases. Sociocognitive deficits underlie most of the problematic social conduct observed in patients and are associated with more negative clinical outcomes (compared to nonsocial cognitive deficits. In clinical settings, social cognition deficits are normally gleaned from collateral information from caregivers or from indirect inferences made from patients’ performance on standard nonsocial cognitive tests. Information from these sources is however inadequate. I discuss key social cognition functions, focusing initially on deficits in emotion perception and theory of mind, two areas that have gained sizeable attention in neuroscientific research, and then extend the discussion into relatively new, less covered but crucial functions involving empathic behaviour, social awareness, social judgements, and social decision making. These functions are frequently impaired following neurological change. At present, a wide range of psychometrically robust social cognition tests is available, and this review also makes the case for their inclusion in neuropsychological assessments.
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…
Verstraeten, S.M.M.; Mark, R.E.; Sitskoorn, M.M.
Background: The prevalence of both motor deficit and cognitive impairment after stroke is high and persistent. Motor impairment, especially paresis, is often ore obvious to both patients and their carers while cognitive problems can also have devastating effects on quality of life. The current
Gong, Liang; Yin, Yingying; He, Cancan; Ye, Qing; Bai, Feng; Yuan, Yonggui; Zhang, Haisan; Lv, Luxian; Zhang, Hongxing; Xie, Chunming; Zhang, Zhijun
Neuroimaging studies have demonstrated that major depressive disorder (MDD) patients show blunted activity responses to reward-related tasks. However, whether abnormal reward circuits affect cognition and depression in MDD patients remains unclear. Seventy-five drug-naive MDD patients and 42 cognitively normal (CN) subjects underwent a resting-state functional magnetic resonance imaging scan. The bilateral nucleus accumbens (NAc) were selected as seeds to construct reward circuits across all subjects. A multivariate linear regression analysis was employed to investigate the neural substrates of cognitive function and depression severity on the reward circuits in MDD patients. The common pathway underlying cognitive deficits and depression was identified with conjunction analysis. Compared with CN subjects, MDD patients showed decreased reward network connectivity that was primarily located in the prefrontal-striatal regions. Importantly, distinct and common neural pathways underlying cognition and depression were identified, implying the independent and synergistic effects of cognitive deficits and depression severity on reward circuits. This study demonstrated that disrupted topological organization within reward circuits was significantly associated with cognitive deficits and depression severity in MDD patients. These findings suggest that in addition to antidepressant treatment, normalized reward circuits should be a focus and a target for improving depression and cognitive deficits in MDD patients. Copyright Â© 2016 Elsevier Ltd. All rights reserved.
Full Text Available Schizophrenia is a brain disorder associated with cognitive deficits that severely affect the patients' capacity for daily functioning. Whereas our understanding of its pathophysiology is limited, postmortem studies suggest that schizophrenia is associated with deficits of GABA-mediated synaptic transmission. A major role of GABA-mediated transmission may be producing synchronized network oscillations which are currently hypothesized to be essential for normal cognitive function. Therefore, cognitive deficits in schizophrenia may result from a GABA synapse dysfunction that disturbs neural synchrony. Here, we highlight recent studies further suggesting alterations of GABA transmission and network oscillations in schizophrenia. We also review current models for the mechanisms of GABA-mediated synchronization of neural activity, focusing on parvalbumin-positive GABA neurons, which are altered in schizophrenia and whose function has been strongly linked to the production of neural synchrony. Alterations of GABA signaling that impair gamma oscillations and, as a result, cognitive function suggest paths for novel therapeutic interventions.
Gonzalez-Burgos, Guillermo; 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, cognitive deficits in schizophrenia may result from a GABA synapse dysfunction that disturbs neural synchrony. Here, we highlight recent studies further suggesting alterations of GABA transmission and network oscillations in schizophrenia. We also review current models for the mechanisms of GABA-mediated synchronization of neural activity, focusing on parvalbumin-positive GABA neurons, which are altered in schizophrenia and whose function has been strongly linked to the production of neural synchrony. Alterations of GABA signaling that impair gamma oscillations and, as a result, cognitive function suggest paths for novel therapeutic interventions.
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...
Leiser, Steven C; Bowlby, Mark R; Comery, Thomas A; Dunlop, John
Cognition, memory, and attention and arousal have been linked to nicotinic acetylcholine receptors (nAChRs). Thus it is not surprising that nAChRs have been strongly implicated as therapeutic targets for treating cognitive deficits in disorders such as schizophrenia and Alzheimer's disease (AD). In particular the alpha7 (alpha7) nAChR has been closely linked with normalization of P50 auditory evoked potential (AEP) gating deficits, and to a lesser extent improvements in pre-pulse inhibition (PPI) of the acoustic startle response. These two brain phenomena can be considered as pre-attentive, occurring while sensory information is being processed, and are important endophenotypes in schizophrenia with deficits likely contributing to the cognitive fragmentation associated with the disease. In addition alpha7 nAChRs have been implicated in attention, in particular under high attentional demand, and in more demanding working memory tasks such as long delays in delayed matching tasks. Efficacy of alpha7 nAChR agonists across a range of cognitive processes ranging from pre-attentive to attentive states and working and recognition memory provides a solid basis for their pro-cognitive effects. This review will focus on the recent work highlighting the role of alpha7 in cognition and cognitive processes.
Full Text Available Maternal exposure to infectious agents is a predisposing factor for schizophrenia with associated cognitive deficits in offspring. A high incidence of smoking in these individuals in adulthood might be, at least in part, due to the cognitive-enhancing effects of nicotine. Here, we have used prenatal exposure to maternal lipopolysaccharide (LPS, bacterial endotoxin at different time points as a model for cognitive deficits in schizophrenia to determine whether nicotine reverses any associated impairments. Pregnant rats were treated subcutaneously with LPS (0.5 mg/kg at one of three neurodevelopmental time periods [gestation days (GD 10-11, 15-16, 18-19]. Cognitive assessment in male offspring commenced in early adulthood [postnatal day (PND 60] and included: prepulse inhibition (PPI, latent inhibition (LI and delayed non-matching to sample (DNMTS. Following PND 100, daily nicotine injections (0.6 mg/kg, subcutaneously were administered, and animals were re-tested in the same tasks (PND 110. Only maternal LPS exposure early during fetal neurodevelopment (GD 10-11 resulted in deficits in all tests compared to animals that had been prenatally exposed to saline at the same gestational time point. Repeated nicotine treatment led to global (PPI and selective (LI improvements in performance. Early but not later prenatal LPS exposure induced consistent deficits in cognitive tests with relevance for schizophrenia. Nicotine reversed the LPS-induced deficits in selective attention (LI and induced a global enhancement of sensorimotor gating (PPI.
Bui, Kevin D; Rai, Roshan; Johnson, Michelle J
In this study, we aim to explore ways to objectively assess cognitive deficits in the stroke and HIV/stroke populations, where cognitive and motor impairments can be hard to separate. Using an upper limb rehabilitation robot called the Haptic TheraDrive, we collect performance error scores and motor learning data on the impaired and unimpaired limb during a trajectory tracking task. We compare these data to clinical cognitive scores. The preliminary results suggest a possible relationship between unimpaired upper limb performance error and visuospatial/executive function cognitive domains, but more work needs to be done to further investigate this. The potential of using robot-assisted technologies to measure unimpaired limb kinematics as a tool to assess cognitive deficits would be useful to inform more effective rehabilitation strategies for HIV, stroke, and HIV/stroke populations.
Danese, Andrea; Moffitt, Terrie E; Arseneault, Louise; Bleiberg, Ben A; Dinardo, Perry B; Gandelman, Stephanie B; Houts, Renate; Ambler, Antony; Fisher, Helen; Poulton, Richie; Caspi, Avshalom
OBJECTIVE Individuals reporting a history of childhood violence victimization have impaired brain function. However, the clinical significance, reproducibility, and causality of these findings are disputed. We directly tested these research gaps. METHOD We tested the association between prospectively-collected measures of childhood violence victimization and cognitive functions in childhood, adolescence, and adulthood among 2,232 members of the UK E-Risk Study and 1,037 members of the New Zealand Dunedin Study, who were followed-up from birth until ages 18 and 38 years, respectively. We used multiple measures of victimization and cognition, and included comparisons of cognitive scores for twins discordant for victimization. RESULTS We found that individuals exposed to childhood victimization had pervasive impairments in clinically-relevant cognitive functions including general intelligence, executive function, processing speed, memory, perceptual reasoning, and verbal comprehension in adolescence and adulthood. However, the observed cognitive deficits in victimized individuals were largely explained by cognitive deficits that predated childhood victimization and by confounding genetic and environmental risks. CONCLUSIONS Findings from two population-representative birth cohorts totaling more than 3,000 individuals and born 20 years and 20,000 kilometers apart suggest that the association between childhood violence victimization and later cognition is largely non-causal, in contrast to conventional interpretations. These findings urge adopting a more circumspect approach to causal inference in the neuroscience of stress. Clinically, cognitive deficits should be conceptualized as individual risk factors for victimization as well as potential complicating features during treatment. PMID:27794691
Utami, N.; Effendy, E.; Amin, M. M.
Schizophrenia is a complex neurodevelopmental disorder with cognitive impairment as the main part. BDNF regulates aspects of developmental plasticity in the brain and is involved in cognitive function. Cognitive functions include capabilities such as attention, executive functioning, assessing, monitoring and evaluating. The aim of the study was to know the BDNF levels in schizophrenic patients with cognitive deficits. The study was held in October 2016 - March 2017, and was the first in Indonesia, especially in North Sumatra. The study was approved by the medical ethics committee of the University of North Sumatera. The study is descriptive based on a retrospective method with cross-sectional approach. The subject is 40 male schizophrenia. Cognitive deficits were assessed by MoCA-Ina. BDNF serum levels were analyzed using the quantitative sandwich enzyme immunoassay. The average MoCA-Ina score is 21.03±5.21. This suggests that there is a cognitive function deficit in schizophrenic patients. The mean serum BDNF level was 26629±6762. MoCA-Ina scores in schizophrenic patients <26 who experienced a deficit of 77.5% and serum BDNF levels with normal values ranging from 6.186 to 42.580pg/ml.
Liu, Xiao; Li, Jitao; Guo, Chunmei; Wang, Hongli; Sun, Yaxin; Wang, Han; Su, Yun-Ai; Li, Keqing; Si, Tianmei
Cognitive dysfunction constitutes an essential component in schizophrenia for its early presence in the pathophysiology of the disease and close relatedness to life quality of patients. To develop effective treatment of cognitive deficits, it is important to understand their neurobiological causes and to identify potential therapeutic targets. In this study, adopting repeated MK-801 treatment as an animal model of schizophrenia, we investigated whether antipsychotic drugs, olanzapine and haloperidol, can reverse MK-801-induced cognitive deficits and how the reversal processes recruited proteins involved in glutamate neurotransmission in rat medial prefrontal cortex (mPFC) and hippocampus. We found that low-dose chronic MK-801 treatment impaired object-in-context recognition memory and reversal learning in the Morris water maze, leaving reference memory relatively unaffected, and that these cognitive deficits can be partially reversed by olanzapine, not haloperidol, treatment. At the molecular level, chronic MK-801 treatment resulted in the reduction of multiple N-methyl-D-aspartate (NMDA) receptor subunits in rat mPFC and olanzapine, not haloperidol, treatment restored the levels of GluN1 and phosphorylated GluN2B in this region. Taken together, MK-801-induced cognitive deficits may be associated with region-specific changes in NMDA receptor subunits and the reversal of specific NMDA receptor subunits may underlie the cognition-enhancing effects of olanzapine. PMID:29375333
Purpose: To evaluate the protective effect of melatonin on diabetes-induced cognitive dysfunction. Methods: Rats ... suggests that melatonin may be useful for the management of cognitive dysfunction in patients suffering ... as amyotrophic lateral sclerosis, Alzheimer's disease ..... with the inhibitory kappa beta (Iκβ) family.
van Duijvenbode, Neomi; Didden, Robert; VanDerNagel, Joanne El; Korzilius, Hubert Plm; Engels, Rutger Cme
We examined cognitive deficits in problematic drinkers with and without mild to borderline intellectual disability (MBID). Problematic drinkers were expected to show a significantly lower estimated performance IQ (PIQ), but not a lower estimated verbal IQ (VIQ), compared to light drinkers. Participants ( N = 474) were divided into four groups based on IQ and severity of alcohol use-related problems. IQ was estimated using (a short form of) the Wechsler Adult Intelligence Scale third edition. Severity of alcohol use-related problems was assessed using the Alcohol Use Disorder Identification Test. Overall, there were no significant differences between light and problematic drinkers on estimated VIQ. Within the group without MBID, estimated PIQ was significantly lower. Estimated PIQ was not lower in problematic drinkers with MBID compared to light drinkers with MBID. The results are indicative of cognitive deficits in problematic drinkers without MBID. Screening for cognitive deficits with additional instruments is advised.
Nordlund, Arto; Berggren, Jens; Holmström, Alexandra; Fu, Michael; Wallin, Anders
The objective of the present study was to investigate whether mild cognitive deficits are present in patients with heart failure (HF) despite absence of any known cognitive disorder. A well defined group of patients (n = 40) with heart failure completed a cognitive screening check list, a depression screening questionnaire, and a battery consisting of neuropsychological tests assessing 5 different cognitive domains: speed/attention, episodic memory, visuospatial functions, language, and executive functions. The neuropsychological results were compared with those from a group of healthy control subjects (n = 41). The patients with HF displayed cognitive impairment compared with the control group within the domains speed and attention, episodic memory, visuospatial functions, and language. Among them, 34 HF patients (85%) could be classified with mild cognitive impairment (MCI), the majority as nonamnestic MCI, ie, with no memory impairment. Considering the high occurrence of mild cognitive deficits among HF patients without known cognitive disorders, closer attention should be paid to their self-care and compliance. Inadequate self-care and compliance could lead to more frequent hospitalizations. Furthermore, the HF patients may be at increased risk of dementia. Copyright © 2015 Elsevier Inc. All rights reserved.
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: 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); 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: 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); 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.
Wu, Dong-mei; Lu, Jun; Zhang, Yan-qiu; Zheng, Yuan-lin; Hu, Bin; Cheng, Wei; Zhang, Zi-feng; Li, Meng-qiu
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
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 prof......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 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 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...
Klamer, Anja; Lando, Ane; Pinborg, Anja
AIM: To validate the Ages and Stages Questionnaire (ASQ) and to measure average cognitive deficit in children born extremely preterm. METHODS: Parents of 30 term children aged 36-42 mo completed the ASQ and the children underwent the Wechsler Preschool and Primary Scales of Intelligence--Revised.......AIM: To validate the Ages and Stages Questionnaire (ASQ) and to measure average cognitive deficit in children born extremely preterm. METHODS: Parents of 30 term children aged 36-42 mo completed the ASQ and the children underwent the Wechsler Preschool and Primary Scales of Intelligence...
Full Text Available Jeremy Cosgrove, Jane Elizabeth Alty Department of Neurology, Leeds Teaching Hospitals NHS Trust, Leeds, UK Abstract: Cognitive dysfunction is a common and significant non-motor symptom of Parkinson’s disease (PD. PD mild cognitive impairment (PD-MCI is evident in approximately one-quarter of patients at the time of PD diagnosis, and half of PD patients have progressed to PD dementia (PDD after 10 years. The transition to PDD from PD-MCI is not linear and may depend on the facets of cognition affected. Despite increased understanding of pathological, neurotransmitter and genetic drivers, there are no proven pharmacological treatments for PD-MCI and those licensed for PDD are of modest benefit only. Biomarkers to predict those most at risk of developing PDD are under investigation and are likely to be essential so that early and individualized treatment can be provided. Keywords: Parkinson’s disease, mild cognitive impairment, dementia
Bikic, Aida; Leckman, James F; Lindschou, Jane
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...... 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...... 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...
Wang, Jingjuan; Zhou, Li; Cui, Chunlei; Liu, Zhening; Lu, Jie
Cognitive deficits are a core feature of early schizophrenia. However, the pathological foundations underlying cognitive deficits are still unknown. The present study examined the association between gray matter density and cognitive deficits in first-episode schizophrenia. Structural magnetic resonance imaging of the brain was performed in 34 first-episode schizophrenia patients and 21 healthy controls. Patients were divided into two subgroups according to working memory task performance. The three groups were well matched for age, gender, and education, and the two patient groups were also further matched for diagnosis, duration of illness, and antipsychotic treatment. Voxel-based morphometric analysis was performed to estimate changes in gray matter density in first-episode schizophrenia patients with cognitive deficits. The relationships between gray matter density and clinical outcomes were explored. Patients with cognitive deficits were found to have reduced gray matter density in the vermis and tonsil of cerebellum compared with patients without cognitive deficits and healthy controls, decreased gray matter density in left supplementary motor area, bilateral precentral gyrus compared with patients without cognitive deficits. Classifier results showed GMD in cerebellar vermis tonsil cluster could differentiate SZ-CD from controls, left supplementary motor area cluster could differentiate SZ-CD from SZ-NCD. Gray matter density values of the cerebellar vermis cluster in patients groups were positively correlated with cognitive severity. Decreased gray matter density in the vermis and tonsil of cerebellum may underlie early psychosis and serve as a candidate biomarker for schizophrenia with cognitive deficits.
McClure, Erin B; Treland, Julia E; Snow, Joseph; Schmajuk, Mariana; Dickstein, Daniel P; Towbin, Kenneth E; Charney, Dennis S; Pine, Daniel S; Leibenluft, Ellen
Little is known about neuropsychological and social-cognitive function in patients with pediatric bipolar disorder. Identification of specific deficits and strengths that characterize pediatric bipolar disorder would facilitate advances in diagnosis, treatment, and research on pathophysiology. The purpose of this study was to test the hypothesis that youths with bipolar disorder would perform more poorly than matched healthy comparison subjects on measures of social cognition, motor inhibition, and response flexibility. Forty outpatients with pediatric bipolar disorder and 22 comparison subjects (no differences in age, gender, and IQ) completed measures of social cognition (the pragmatic judgment subtest of the Comprehensive Assessment of Spoken Language, facial expression recognition subtests of the Diagnostic Analysis of Nonverbal Accuracy Scale, the oral expression subtest of the Test of Language Competence), inhibition and response flexibility (stop and stop-change tasks), and motor inhibition (continuous performance tasks). Pediatric bipolar disorder patients performed more poorly than comparison subjects on social-cognitive measures (pragmatic judgment of language, facial expression recognition) and on a task requiring response flexibility. These deficits were present in euthymic patients. Differences between patients and comparison subjects could not be attributed to comorbid attention deficit hyperactivity disorder. Findings of impaired social cognition and response flexibility in youths with pediatric bipolar disorder suggest continuity between pediatric bipolar disorder and adult bipolar disorder. These findings provide a foundation for neurocognitive research designed to identify the neural mechanisms underlying these deficits.
Kennelly, K J; Hayslip, B; Richardson, S K
Sixty-six community-residing elderly (mean age = 72.5) were categorized as depressed (mean = 11.3) or nondepressed (mean = 3.9) based on Beck Depression Inventory scores. After a pre-test battery measuring short-term memory and crystallized/fluid intelligence, the subjects responded to a word association task, disguised as a test of interpersonal empathy, under response dependent or response independent reinforcement conditions, or were assigned to a no treatment control. A post-test battery of alternate forms followed. Four of seven measures showed significant pre- to post-test declines in performance. For two of these four, response dependent reinforcement prevented otherwise significant declines. With pre-test differences statistically controlled, depression produced significant post-test deficits in three measures. Response dependent reinforcement eliminated this depression deficit in one measure. The results indicate that depression may exacerbate fatigue effects for the elderly and response dependent reinforcement may prevent fatigue-caused deficits in short-term 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...... heterogeneity in the clinical presentation of awareness. The results demonstrate that subjective memory problems should not be a mandatory prerequisite in suspected dementia or MCI, which makes reports from informants together with thorough clinical interview and observation central when assessing suspected...
Fitri Genisti; Ni Komang Sukra Andini; Ni Luh Gede Puspita Yanti
Background: Child development is a very important phase, which children learn various skills as future generations in the future. Disorders that can impede child development process of Attention Deficit Hyperactivity Disorder (ADHD). Children with ADHD have problems with cognitive abilities, of which about 20-60% of them have learning disorders. The efforts to support cognitive development in ADHD children is to approach the child's environment through parenting parents. Objective: This s...
Oliveira, Anderson Souza; Reiche, Mikkel Staall; Vinescu, Cristina Ioana
Aging reduces cognitive functions, and such impairments have implications in mental and motor performance. Cognitive function has been recently linked to the risk of falls in older adults. Physical activities have been used to attenuate the declines in cognitive functions and reduce fall incidence......, but little is known whether a physically active lifestyle can maintain physical performance under cognitively demanding conditions. The aim of this study was to verify whether physically active older adults present similar performance deficits during upper limb response time and precision stepping walking...... tasks when compared to younger adults. Both upper limb and walking tasks involved simple and complex cognitive demands through decision-making. For both tasks, decision-making was assessed by including a distracting factor to the execution. The results showed that older adults were substantially slower...
Wen, Yi; Nie, Xueqing; Wu, Daxing; Liu, Hong; Zhang, Pin; Lu, Xuejing
The current study explored the music perception ability of individuals diagnosed with schizophrenia and its relationship with other cognitive abilities and psychotic symptom severity. The persons with schizophrenia performed significantly worse than the control group on the Montreal Battery of Evaluation of Amusia (MBEA) (p<0.001). The music perception ability of persons with schizophrenia was related to other cognitive abilities (attention, verbal memory, spatial memory, and executive function) and the severity of psychotic symptoms. Copyright © 2014 Elsevier B.V. All rights reserved.
Savaskan, Egemen; Summermatter, Daniel; Schroeder, Clemens; Schächinger, Hartmut
Faces are among the most relevant social stimuli revealing an encounter's identity and actual emotional state. Deficits in facial recognition may be an early sign of cognitive decline leading to social deficits. The main objective of the present study is to investigate if individuals with amnestic mild cognitive impairment show recognition deficits in facial identity. Thirty-seven individuals with amnestic mild cognitive impairment, multiple-domain (15 female; age: 75±8 yrs.) and forty-one healthy volunteers (24 female; age 71±6 yrs.) participated. All participants completed a human portrait memory test presenting unfamiliar faces with happy and angry emotional expressions. Five and thirty minutes later, old and new neutral faces were presented, and discrimination sensitivity (d') and response bias (C) were assessed as signal detection parameters of cued facial identity recognition. Memory performance was lower in amnestic mild cognitive impairment as compared to control subjects, mainly because of an altered response bias towards an increased false alarm rate (favoring false OLD ascription of NEW items). In both groups, memory performance declined between the early and later testing session, and was always better for acquired happy than angry faces. Facial identity memory is impaired in patients with amnestic mild cognitive impairment. Liberalization of the response bias may reflect a socially motivated compensatory mechanism maintaining an almost identical recognition hit rate of OLD faces in individuals with amnestic mild cognitive impairment.
Viswanath, Biju; Harihara, Shashidhara N; Nahar, Abhinav; Phutane, Vivek Haridas; Taksal, Aarati; Thirthalli, Jagadisha; Gangadhar, Bangalore N
The use of electroconvulsive therapy (ECT) in treatment of psychiatric disorders is associated with adverse cognitive effects. There is a need to develop a short assessment tool of cognitive functions during the course of ECT. This study aimed at developing and validating a short, sensitive battery to assess cognitive deficits associated with ECT in India. Battery for ECT Related Cognitive Deficits (B4ECT-ReCoDe), a brief cognitive battery (20-30 min) to assess verbal, visual, working and autobiographic memory, sustained attention, psychomotor speed and subjective memory impairment, was administered to 30 in-patients receiving bilateral ECT, one day after the 1st, 3rd and 6th ECT. Data was analysed using repeated measures analysis of variance and Pearson's correlation. Significant deficits were found in verbal, visual and autobiographic memory, psychomotor speed. Subjective experience of memory loss correlated positively with verbal memory impairment. B4ECT-ReCoDe, a brief, sensitive measure of cognitive impairments associated with ECT can be used in routine clinical practice. Copyright © 2013 Elsevier B.V. All rights reserved.
Jütten, L.H.; Mark, R.E.; Sitskoorn, M.M.
Recent research suggests that informal caregivers of people with dementia (ICs) experience more cognitive deficits than noncaregivers. The reason for this is not yet clear. Objective: to test the hypothesis that ICs ‘mirror' the cognitive deficits of the demented people they care for. Participants
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.…
Taphoorn, M.J.B.; Klein, M.
Cognitive function, with survival and response on brain imaging, is increasingly regarded as an important outcome measure in patients with brain tumours. This measure provides us with information on a patient's clinical situation and adverse treatment effects. Radiotherapy has been regarded as the
Jiao, Shu-Sheng; Yao, Xiu-Qing; Liu, Yu-Hui; Wang, Qing-Hua; Zeng, Fan; Lu, Jian-Jun; Liu, Jia; Zhu, Chi; Shen, Lin-Lin; Liu, Cheng-Hui; Wang, Ye-Ran; Zeng, Gui-Hua; Parikh, Ankit; Chen, Jia; Liang, Chun-Rong; Xiang, Yang; Bu, Xian-Le; Deng, Juan; Li, Jing; Xu, Juan; Zeng, Yue-Qin; Xu, Xiang; Xu, Hai-Wei; Zhong, Jin-Hua; Zhou, Hua-Dong; Zhou, Xin-Fu; Wang, Yan-Jiang
Alzheimer's disease (AD) is one of most devastating diseases affecting elderly people. Amyloid-β (Aβ) accumulation and the downstream pathological events such as oxidative stress play critical roles in pathogenesis of AD. Lessons from failures of current clinical trials suggest that targeting multiple key pathways of the AD pathogenesis is necessary to halt the disease progression. Here we show that Edaravone, a free radical scavenger that is marketed for acute ischemic stroke, has a potent capacity of inhibiting Aβ aggregation and attenuating Aβ-induced oxidation in vitro. When given before or after the onset of Aβ deposition via i.p. injection, Edaravone substantially reduces Aβ deposition, alleviates oxidative stress, attenuates the downstream pathologies including Tau hyperphosphorylation, glial activation, neuroinflammation, neuronal loss, synaptic dysfunction, and rescues the behavioral deficits of APPswe/PS1 mice. Oral administration of Edaravone also ameliorates the AD-like pathologies and memory deficits of the mice. These findings suggest that Edaravone holds a promise as a therapeutic agent for AD by targeting multiple key pathways of the disease pathogenesis.
Jekel, K.; Damian, M.; Wattmo, C.; Hausner, L.; Bullock, R.; Connelly, P.J.; Dubois, B.; Eriksdotter, M.; Ewers, M.; Graessel, E.; Kramberger, M.G.; Law, E.; Mecocci, P.; Molinuevo, J.L.; Nygard, L.; Olde Rikkert, M.G.M.; Orgogozo, J.M.; Pasquier, F.; Peres, K.; Salmon, E.; Sikkes, S.A.; Sobow, T.; Spiegel, R.; Tsolaki, M.; Winblad, B.; Frolich, L.
INTRODUCTION: There is a growing body of evidence that subtle deficits in instrumental activities of daily living (IADL) may be present in mild cognitive impairment (MCI). However, it is not clear if there are IADL domains that are consistently affected across patients with MCI. In this systematic
Abada, Yah-se K.; Schreiber, Rudy; Ellenbroek, Bart
Rationale: Huntington's disease (HD) is characterized by progressive motor dysfunction, emotional disturbances and cognitive deficits. It is a genetic disease caused by an elongation of the polyglutamine repeats in the huntingtin gene. Whereas HD is a complex disorder, previous studies in mice
Conclusion: The results indicate that parents' initial concerns about their children's multiple or speech developmental problems were relatively highly correlated with cognitive deficits. It is recommended that clinicians should guide parents to voice and organize their concerns regarding the perception of their children's developmental progress, and further precisely analyze and utilize significant information.
Joosen, M.J.A.; Jousma, E.; van den Boom, T.M.; Kuijpers, W.C.; Smit, A.B.; Lucassen, P.J.; van Helden, H.P.M.
To date, treatment of organophosphate (OP) poisoning shows several shortcomings, and OP-victims might suffer from lasting cognitive deficits and sleep-wake disturbances. In the present study, long-term effects of soman poisoning on learning ability, memory and neurogenesis were investigated in rats,
Carmona, Susana; Hoekzema, E; 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
Attention skills are strongly associated with academic attainment, social inclusion, peer relationships and mental health. Attention difficulties are commonly reported in children with intellectual and developmental disabilities (IDD), consequently increasing the already heightened risk of cognitive difficulties, behavioural problems and learning impairments. Despite acknowledgement of the core deficits in attention that characterise children with IDD, limited research has attempted to stre...
Klamer, Anja; Lando, Ane; Pinborg, Anja
AIM: To validate the Ages and Stages Questionnaire (ASQ) and to measure average cognitive deficit in children born extremely preterm. METHODS: Parents of 30 term children aged 36-42 mo completed the ASQ and the children underwent the Wechsler Preschool and Primary Scales of Intelligence...
Duijvenbode, N. van; Didden, H.C.M.; Nagel, J.E.L. van der; Korzilius, H.P.L.M.; Engels, R.C.M.E.
We examined cognitive deficits in problematic drinkers with and without mild to borderline intellectual disability (MBID). Problematic drinkers were expected to show a significantly lower estimated performance IQ (PIQ), but not a lower estimated verbal IQ (VIQ), compared to light drinkers.
Roks, G.; Sistermans, E.A.; Vries, L.B.A. de; Nijssen, P.C.
A 75-year-old man had progressive difficulty with walking, intention tremor, ataxia, and mild cognitive deficits. MRI scan ofthe brain showed symmetrical hyperintensities in the middle cerebellar peduncles. DNA analysis ofthe fragile-X gene revealed an expansion of 150-200 repetitions in the
Davis, Andrew S; Trotter, Jeffrey S; Hertza, Jeremy; Bell, Christopher D; Dean, Raymond S
The purpose of this study was to examine the presence of finger agnosia in patients with Alzheimer's disease (AD) and to determine if level of finger agnosia was related to cognitive impairment. Finger agnosia is a sensitive measure of cerebral impairment and is associated with neurofunctional areas implicated in AD. Using a standardized and norm-referenced approach, results indicated that patients with AD evidenced significantly decreased performance on tests of bilateral finger agnosia compared with healthy age-matched controls. Finger agnosia was predictive of cognitive dysfunction on four of seven domains, including: Crystallized Language, Fluid Processing, Associative Learning, and Processing Speed. Results suggest that measures of finger agnosia, a short and simple test, may be useful in the early detection of AD.
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 - Neuro logy Impact factor: 9.598, year: 2007
Kesby, James P.; Markou, Athina; Semenova, Svetlana
Methamphetamine abuse is common among individuals infected by human immunodeficiency virus (HIV). Neurocognitive outcomes tend to be worse in methamphetamine users with HIV. However, it is unclear whether discrete cognitive domains are susceptible to impairment after combined HIV infection and methamphetamine abuse. The expression of HIV/gp120 protein induces neuropathology in mice similar to HIV-induced pathology in humans. We investigated the separate and combined effects of methamphetamine exposure and gp120 expression on cognitive function in transgenic (gp120-tg) and control mice. The mice underwent an escalating methamphetamine binge regimen and were tested in novel object/location recognition, object-in-place recognition, and Barnes maze tests. gp120 expression disrupted performance in the object-in-place test (i.e., similar time spent with all objects, regardless of location), indicating deficits in associative recognition memory. gp120 expression also altered reversal learning in the Barnes maze, suggesting impairments in executive function. Methamphetamine exposure impaired spatial strategy in the Barnes maze, indicating deficits in spatial learning. Methamphetamine-exposed gp120-tg mice had the lowest spatial strategy scores in the final acquisition trials in the Barnes maze, suggesting greater deficits in spatial learning than all of the other groups. Although HIV infection involves interactions between multiple proteins and processes, in addition to gp120, our findings in gp120-tg mice suggest that humans with the dual insult of HIV infection and methamphetamine abuse may exhibit a broader spectrum of cognitive deficits than those with either factor alone. Depending on the cognitive domain, the combination of both insults may exacerbate deficits in cognitive performance compared with each individual insult. PMID:25476577
Full Text Available Background: Some studies have demonstrated high cognitive deficits in patients with post-traumatic stress disorder (PTSD. Considering the limited available information about this issue, we decided to assess the cognitive deficits and memory disturbances in these patients.Materials and Methods: The present study is a case control research conducted on 50 patients with post-traumatic stress disorder who were admitted to Ibn-e-Sina psychiatric hospital in Mashhad, in north-eastern part of Iran in 2008. The control group included 50 people of first degree relatives of these patients who met the inclusion criteria of the study. Case and control groups were selected by simple sampling method; and for all of them, a questionnaire of demographic information, Wechsler memory scale, and mini mental status examination (MMSE were completed. The gathered data were analyzed using SPSS 14th edition by chi square, t-test, and analyze of variance.Results: The mean score of Wechsler memory scale in patients with PTSD (80.78±18.39 was significantly higher than control group (67.92±7.38 (p=0.001. The mean score of MMSE was significantly lower in patients with PTSD compared to control group (p=0.001. The determined disability level assessed by Iranian veterans’ organization and also comorbidity of other psychiatric disorders with PTSD did not have a significant relationship with cognitive deficits, but the duration of PTSD and age of patients were significantly related to the level of cognitive deficits.Conclusion: Cognitive deficits and memory disturbances are higher in patients with PTSD than general population.
Qu, Jie; Zhou, Qiong; Du, Ying; Zhang, Wei; Bai, Miao; Zhang, Zhuo; Xi, Ye; Li, Zhuyi; Miao, Jianting
Chronic cerebral hypoperfusion is a critical causative factor for the development of cognitive decline and dementia in the elderly, which involves many pathophysiological processes. Consequently, inhibition of several pathophysiological pathways is an attractive therapeutic strategy for this disorder. Rutin, a biologically active flavonoid, protects the brain against several insults through its antioxidant and anti-inflammatory properties, but its effect on cognitive deficits and brain damage caused by chronic cerebral hypoperfusion remains unknown. Here, we investigated the neuroprotective effect of rutin on cognitive impairments and the potential mechanisms underlying its action in rats with chronic cerebral hypoperfusion. We used Sprague-Dawley rats with permanent bilateral common carotid artery occlusion (BCCAO), a well-established model of chronic cerebral hypoperfusion. After rutin treatment for 12 weeks, the neuroprotective effect of rutin in rats was evaluated by behavioural tests, biochemical and histopathological analyses. BCCAO rats showed marked cognitive deficits, which were improved by rutin treatment. Moreover, BCCAO rats exhibited central cholinergic dysfunction, oxidative damage, inflammatory responses and neuronal damage in the cerebral cortex and hippocampus, compared with sham-operated rats. All these effects were significantly alleviated by treatment with rutin. Our results provide new insights into the pharmacological actions of rutin and suggest that rutin has multi-targeted therapeutical potential on cognitive deficits associated with conditions with chronic cerebral hypoperfusion such as vascular dementia and Alzheimer's disease. © 2014 The British Pharmacological Society.
Cerebral blood flow pattern in Parkinson's disease was examined by 123 I-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 123 I-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)
Bodnar, Anna; Rybakowski, Janusz K
A number of studies in bipolar patients have shown a deficit in mentalization (theory of mind), one of the main aspects of social cognition. The aim of current study was to assess both cognitive and affective mentalization in well-defined groups of depressed and manic bipolar patients, compared to healthy control subjects, using a battery of tests measuring mentalization processes. The second aim was to investigate a possible relationship between cognitive and affective mentalization and cognitive functions in bipolar patients during a depressive and manic episode. The study involved 25 bipolar disorder type I patients (10 male, 15 female) during a depressive episode (mean 24 ± 2 points in the 17-item Hamilton Depression Rating Scale) and 25 patients (10 male, 15 female) during a manic episode (mean 27 ± 4 points in the Young Mania Rating Scale). The control group consisted of 25 healthy subjects (10 male, 15 female) without psychiatric disorders. To measure mentalization, a revised version of the Reading the Mind in the Eyes (R-MET), the Strange Stories (SS), the Faux Pas Recognition (FPR), and the Moving Shapes Paradigm (MSP) tests were used. Assessment of cognitive functioning was made using the Digit Span, Trail Making, and Wisconsin Card Sorting Tests. In bipolar patients significant deficits in both cognitive and affective mentalization were demonstrated during both acute depressive and manic episodes. The impairment in FPR in manic patients was more severe than that in the depressive ones. On the other hand, in MSP, manic patients showed significantly increased intentionality for non-mentalization animations, compared with depressive patients and for "cause and effect" animations compared with control subjects. A significant relationship was found between the decrease in cognitive and affective mentalization and deficits of cognitive functions during both the depressive and manic episodes. The results obtained confirm the deficits of mentalization in
Indra F. Willers
Full Text Available Abstract Mild cognitive impairment (MCI is the transitional stage between normal aging and Alzheimer's disease (AD. Impairments in semantic memory have been demonstrated to be a critical factor in early AD. The Boston Naming Test (BNT is a straightforward method of examining semantic or visuo-perceptual processing and therefore represents a potential diagnostic tool. The objective of this study was to examine naming ability and identify error types in patients with amnestic mild cognitive impairment (aMCI. Methods: Twenty aMCI patients, twenty AD patients and twenty-one normal controls, matched by age, sex and education level were evaluated. As part of a further neuropsychological evaluation, all subjects performed the BNT. A comprehensive classification of error types was devised in order to compare performance and ascertain semantic or perceptual origin of errors. Results: AD patients obtained significantly lower total scores on the BNT than aMCI patients and controls. aMCI patients did not obtain significant differences in total scores, but showed significantly higher semantic errors compared to controls. Conclusion: This study reveals that semantic processing is impaired during confrontation naming in aMCI.
Henderson, V W; Buckwalter, J G
We performed two studies of cognitive abilities among men and women who met clinical criteria for Alzheimer's disease (AD). Among 46 AD patients, performance of women on a composite neuropsychological battery was more impaired than that of men when the potentially confounding effects of demographic variables were controlled; the largest group differences were due to significantly worse performance by women with AD on a naming task. Based on these initial findings, we next analyzed an independent data set of 647 demented subjects enrolled in the multicenter Consortium to Establish a Registry for Alzheimer's Disease, hypothesizing that the naming performance of women with AD would be significantly worse than that of men with this illness. Analyses controlling for demographic variables, or separately controlling for dementia severity, confirmed that women with AD performed significantly less well on the naming task and on verbal fluency. Women also performed less well on delayed recall, but there were no significant differences on other tasks. Factor analysis confirmed significant differences on a language factor, implying that men retain verbal skills better than women do during the initial stages of AD. Elderly nondemented women performed as well as or better than nondemented men on all comparisons. We conclude that there are modest differences in how men and women with AD perform on cognitive tasks and that differences may be discrete rather than global in nature.
Elham Ahmadi Zahrani
Full Text Available Abstract Background: Specific learning disorder is a neurodevelopmental disorder characterized by persistent difficulties in learning academic skills in reading, written expression, or mathematics. This study was performed to investigate the effectiveness of memantine in the relief of cognitive deficits (selective attention, sustained attention, and working memory in specific learning disorder. Materials and Methods: This study is a clinical trial. Of all children 8-12 years referred to Amir Kabir Hospital 94 patients diagnosed with specific learning disorder based on DSMV diagnostic interview referred by specialist and randomly divided by two groups, memantine and placebo. Cognitive deficits before and after treatment were measured with continuous performance test, Stroop test and Wechsler Digit Span forward and reverse and Corsi test. Results: Multivariate analysis of variance showed a significant difference in error when answering, omission answer and corrected answer in continuous performance test, but this difference is not significant in response time. Difference in forward, reverse and collected auditory was significant and not significant in the auditory span. In active visual working memory at corsi cube test, difference was significant (p <0.05. Conclusion: The results showed that memantine in improvement of sustained attention, auditory working memory and visual working memory, is effective, while in selective attention is not effective and according to similarities of learning disorder and Attention deficit / Hyperactivity disorder (ADHD and the effectiveness of memantine in improvement of symptoms of ADHD, we can also use this drug in improvement of cognitive deficits of specific learning disorder.
Thompson, Andrew D; Bartholomeusz, Cali; Yung, Alison R
A number of risk factors for developing a psychotic disorder have been investigated in the 'ultra high risk' (UHR) population, including neurocognitive abilities, social functioning and, more recently, social cognition. We aimed to review the literature on social cognition in the UHR population. Literature was restricted to English articles and identified using Pubmed, Medline, PsychINFO and CINAHLplus, as well as the reference lists of published studies and reviews. Search terms included social cognition, theory of mind, emotion recognition, attributional style, social knowledge, social perception, 'at risk mental state', psychosis prodrome 'clinical high risk' and 'ultra high risk'. Inclusion criteria were an outcome measure of a social cognition task and an UHR population defined by a structured validated instrument. Seven original research articles met the inclusion criteria, one of which was a conference abstract. One of the two studies that assessed theory of mind, two of the four studies that assessed emotion recognition and both the two studies that assessed social perception/knowledge found significant deficits in UHR patients. The single study that assessed attributional bias also reported differences in UHR patients compared with healthy controls. There is limited published literature on social cognitive performance in the UHR population. Despite this, deficits in certain social cognitive abilities do appear to be present, but further research with more reliable cross-cultural measures is needed. The characterization of social cognitive deficits in the UHR populations may aid in the identification of potential markers for development of a subsequent psychotic disorder, as well as targets for early intervention. © 2011 Blackwell Publishing Asia Pty Ltd.
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. (c) 2016 APA, all rights reserved).
Semeijn, E J; Korten, N C M; Comijs, H C; Michielsen, M; Deeg, D J H; Beekman, A T F; Kooij, J J S
Research illustrates cognitive deficits in children and younger adults with attention-deficit/hyperactivity disorder (ADHD). Few studies have focused on the cognitive functioning in older adults. This study investigates the association between ADHD and cognitive functioning in older adults. Data were collected in a cross-sectional side study of the Longitudinal Aging Study Amsterdam (LASA). A diagnostic interview to diagnose ADHD was administered among a subsample (N = 231, age 60-94). ADHD symptoms and diagnosis were assessed with the Diagnostic Interview for ADHD in Adults (DIVA) 2.0. Cognitive functioning was assessed with tests in the domains of executive functioning, information processing speed, memory, and attention/working memory. Regression analyses indicate that ADHD diagnosis and ADHD severity were only negatively associated with cognitive functioning in the attention/working memory domain. When adjusting for depression, these associations were no longer significant. The study shows that ADHD in older adults is associated with lower cognitive functioning in the attention/working memory domain. However, this was partly explained by depressive symptoms.
Anupama V; Bhola, Poornima; Thirthalli, Jagadisha; Mehta, Urvakhsh Meherwan
Social cognition deficits have been implicated in the affect regulation and interpersonal difficulties seen in borderline personality disorder (BPD). The study examined patterns of social cognition abilities, using self-report and task-based measures, among individuals diagnosed with BPD. The sample included a clinical group of 20 patients diagnosed with BPD and 20 age and gender-matched control group participants from the community with no psychiatric diagnosis. The measures included the Mentalization Questionnaire, the Reading the Mind in the Eyes Test and the Social Cognition Rating Tool in Indian Setting. Results indicated that the clinical group had lower self-reported mentalizing ability. Facial emotion recognition ability was significantly lower for the clinical group, particularly for photographs of the eye region with positive and neutral valences. The clinical group had significantly higher personalizing bias, and greater difficulties in social perception. The two groups did not differ on first and second order theory of mind, recognition of faux pas and externalizing bias. The results point to the links between social cognition deficits and interpersonal difficulties among persons with BPD. Implications include the need for pre-therapy assessment of the magnitude and patterns of social cognition difficulties in BPD, the development of culturally and ecologically valid assessments and the evaluation of interventions for social cognition vulnerabilities among individuals with BPD. Copyright © 2018 Elsevier B.V. All rights reserved.
Full Text Available Abstract Background The neuropeptide vasoactive intestinal peptide (VIP is widely distributed in the adult central nervous system where this peptide functions to regulate synaptic transmission and neural excitability. The expression of VIP and its receptors in brain regions implicated in learning and memory functions, including the hippocampus, cortex, and amygdala, raise the possibility that this peptide may function to modulate learned behaviors. Among other actions, the loss of VIP has a profound effect on circadian timing and may specifically influence the temporal regulation of learning and memory functions. Results In the present study, we utilized transgenic VIP-deficient mice and the contextual fear conditioning paradigm to explore the impact of the loss of this peptide on a learned behavior. We found that VIP-deficient mice exhibited normal shock-evoked freezing behavior and increases in corticosterone. Similarly, these mutant mice exhibited no deficits in the acquisition or recall of the fear-conditioned behavior when tested 24-hours after training. The VIP-deficient mice exhibited a significant reduction in recall when tested 48-hours or longer after training. Surprisingly, we found that the VIP-deficient mice continued to express circadian rhythms in the recall of the training even in those individual mice whose wheel running wheel activity was arrhythmic. One mechanistic explanation is suggested by the finding that daily rhythms in the expression of the clock gene Period2 continue in the hippocampus of VIP-deficient mice. Conclusion Together these data suggest that the neuropeptide VIP regulates the recall of at least one learned behavior but does not impact the circadian regulation of this behavior.
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.
Abram, Samantha V; Wisner, Krista M; Fox, Jaclyn M; Barch, Deanna M; Wang, Lei; Csernansky, John G; MacDonald, Angus W; Smith, Matthew J
Impaired cognitive empathy is a core social cognitive deficit in schizophrenia associated with negative symptoms and social functioning. Cognitive empathy and negative symptoms have also been linked to medial prefrontal and temporal brain networks. While shared behavioral and neural underpinnings are suspected for cognitive empathy and negative symptoms, research is needed to test these hypotheses. In two studies, we evaluated whether resting-state functional connectivity between data-driven networks, or components (referred to as, inter-component connectivity), predicted cognitive empathy and experiential and expressive negative symptoms in schizophrenia subjects. Study 1: We examined associations between cognitive empathy and medial prefrontal and temporal inter-component connectivity at rest using a group-matched schizophrenia and control sample. We then assessed whether inter-component connectivity metrics associated with cognitive empathy were also related to negative symptoms. Study 2: We sought to replicate the connectivity-symptom associations observed in Study 1 using an independent schizophrenia sample. Study 1 results revealed that while the groups did not differ in average inter-component connectivity, a medial-fronto-temporal metric and an orbito-fronto-temporal metric were related to cognitive empathy. Moreover, the medial-fronto-temporal metric was associated with experiential negative symptoms in both schizophrenia samples. These findings support recent models that link social cognition and negative symptoms in schizophrenia. Hum Brain Mapp 38:1111-1124, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.
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
Debes, Frodi; Weihe, Pál; Grandjean, Philippe
methylmercury exposure was assessed in terms of the mercury concentration in cord blood and maternal hair. Clinical examinations of 847 cohort members at age 22 years were carried out in 2008-2009 using a panel of neuropsychological tests that reflected major functional domains. Subjects with neurological...... and psychiatric diagnoses were excluded from the data analysis, thus leaving 814 subjects. Multiple regression analysis included covariates previously identified for adjustment. Deficits in Boston Naming Test (BNT) and other tests of verbal performance were significantly associated with the cord-blood mercury...... 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 deficits...
Koelkebeck, Katja; Uwatoko, Teruhisa; Tanaka, Jiro; Kret, Mariska Esther
Social cognitive skills are indispensable for successful communication with others. Substantial research has determined deficits in these abilities in patients with mental disorders. In neurobiological development and continuing into adulthood, cross-cultural differences in social cognition have been demonstrated. Moreover, symptomatic patterns in mental disorders may vary according to the cultural background of an individual. Cross-cultural studies can thus help in understanding underlying (biological) mechanisms and factors that influence behavior in health and disease. In addition, studies that apply novel paradigms assessing the impact of culture on cognition may benefit and advance neuroscience research. In this review, the authors give an overview of cross-cultural research in the field of social cognition in health and in mental disorders and provide an outlook on future research directions, taking a neuroscience perspective.
Nikiforuk, Agnieszka; Gołembiowska, Krystyna; Popik, Piotr
Cognitive impairments associated with schizophrenia await an effective treatment. In order to model schizophrenia-like cognitive deficits in rats, we evaluated the effects of ketamine, a dissociative anesthetic NMDA/glutamate receptor channel blocker in the attentional set-shifting task (ASST). Acute administration of ketamine (10 but not 3mg/kg) selectively impaired solving of the extradimensional (ED) set-shifting component. Next, we investigated whether the co-administration of mazindol, a dopamine and norepinephrine reuptake inhibitor would protect rats from ketamine-induced deficits. Mazindol dose-dependently and selectively alleviated ketamine-induced ED deficit with a minimal effective dose of 0.5mg/kg. The ED component improvement was noted primarily in ketamine - but not in vehicle co-treated rats, in which the drug facilitated ED shift solving at the dose as high as 5mg/kg. A "positive control", sertindole (2.5mg/kg) also ameliorated ketamine-induced ED deficit. Microdialysis of the prefrontal cortex in a separate group of animals revealed that 2-3h after the administration of 5mg/kg of mazindol and ketamine (i.e., at the time of ED component solving), the extracellular concentrations of dopamine were enhanced by ~300% as compared to the baseline and were intermediate between the mazindol- and ketamine-treated reference groups. However, at that time the levels of norepinephrine, serotonin and glutamate appeared unaffected. We conclude that ketamine may be useful in mimicking deficits specifically related to cognitive inflexibility observed in schizophrenia, and suggest that these anomalies could be ameliorated by mazindol. The beneficial effects of mazindol on ASST performance may have therapeutic implications for the treatment of schizophrenia.
Sharpley, Christopher F; Bitsika, Vicki; Christie, David R H
The incidence and contribution to total depression of the depressive symptoms of cognitive deficit and cognitive bias in prostate cancer (PCa) patients were compared from cohorts sampled during the first 2 years after diagnosis. Survey data were collected from 394 patients with PCa, including background information, treatments, and disease status, plus total scores of depression and scores for subscales of the depressive symptoms of cognitive bias and cognitive deficit via the Zung Self-Rating Depression Scale. The sample was divided into eight 3-monthly time-since-diagnosis cohorts and according to depression severity. Mean scores for the depressive symptoms of cognitive deficit were significantly higher than those for cognitive bias for the whole sample, but the contribution of cognitive bias to total depression was stronger than that for cognitive deficit. When divided according to overall depression severity, patients with clinically significant depression showed reversed patterns of association between the two subsets of cognitive symptoms of depression and total depression compared with those patients who reported less severe depression. Differences in the incidence and contribution of these two different aspects of the cognitive symptoms of depression for patients with more severe depression argue for consideration of them when assessing and diagnosing depression in patients with PCa. Treatment requirements are also different between the two types of cognitive symptoms of depression, and several suggestions for matching treatment to illness via a personalized medicine approach are discussed. © The Author(s) 2014.
Fagerlund, Birgitte; Pagsberg, A Katrine; Hemmingsen, Ralf
of 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...... of attention, executive functions, reaction time, and memory in the schizophrenic and psychotic adolescent groups. However, analyses of WISC-III factor profiles suggested that early onset schizophrenia patients may have more global IQ deficits than non-organic, non-affective psychoses when examined recently...... the 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...
He, Hao; Bustillo, Juan; Du, Yuhui; Yu, Qingbao; Jones, Thomas R.; Jiang, Tianzi; Calhoun, Vince D.; Sui, Jing
The cognitive deficits of schizophrenia are largely resistant to current treatment, and are thus a life-long burden to patients. The MATRICS consensus cognitive battery (MCCB) provides a reliable and valid assessment of cognition across a comprehensive set of cognitive domains for schizophrenia. In resting-state fMRI, functional connectivity associated with MCCB has not yet been examined. In this paper, the interrelationships between MCCB and the abnormalities seen in two types of functional measures from resting-state fMRI—fractional amplitude of low frequency fluctuations (fALFF) and functional network connectivity (FNC) maps were investigated in data from 47 schizophrenia patients and 50 age-matched healthy controls. First, the fALFF maps were generated and decomposed by independent component analysis (ICA), and then the component showing the highest correlation with MCCB composite scores was selected. Second, the whole brain was separated into functional networks by group ICA, and the FNC maps were calculated. The FNC strengths with most significant correlations with MCCB were displayed and spatially overlapped with the fALFF component of interest. It demonstrated increased cognitive performance associated with higher fALFF values (intensity of regional spontaneous brain activity) in prefrontal regions, inferior parietal lobe (IPL) but lower ALFF values in thalamus, striatum, and superior temporal gyrus (STG). Interestingly, the FNC showing significant correlations with MCCB were in well agreement with the activated regions with highest z-values in fALFF component. Our results support the view that functional deficits in distributed cortico-striato-thalamic circuits and inferior parietal lobe may account for several aspects of cognitive impairment in schizophrenia.
Le Berre, Anne-Pascale; Fama, Rosemary; Sullivan, Edith V
Alcoholism is a complex and dynamic disease, punctuated by periods of abstinence and relapse, and influenced by a multitude of vulnerability factors. Chronic excessive alcohol consumption is associated with cognitive deficits, ranging from mild to severe, in executive functions, memory, and metacognitive abilities, with associated impairment in emotional processes and social cognition. These deficits can compromise efforts in initiating and sustaining abstinence by hampering efficacy of clinical treatment and can obstruct efforts in enabling good decision making success in interpersonal/social interactions, and awareness of cognitive and behavioral dysfunctions. Despite evidence for differences in recovery levels of selective cognitive processes, certain deficits can persist even with prolonged sobriety. Herein is presented a review of alcohol-related cognitive impairments affecting component processes of executive functioning, memory, and the recently investigated cognitive domains of metamemory, social cognition, and emotional processing; also considered are trajectories of cognitive recovery with abstinence. Finally, in the spirit of critical review, limitations of current knowledge are noted and avenues for new research efforts are proposed that focus on (i) the interaction among emotion-cognition processes and identification of vulnerability factors contributing to the development of emotional and social processing deficits and (ii) the time line of cognitive recovery by tracking alcoholism's dynamic course of sobriety and relapse. Knowledge about the heterochronicity of cognitive recovery in alcoholism has the potential of indicating at which points during recovery intervention may be most beneficial. Copyright © 2017 by the Research Society on Alcoholism.
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
Colucci, Luisa; Bosco,; Amenta,; Fasanaro,Angiola Maria; Ziello,Antonio; Rea,
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 ...
Schmader, Toni; Forbes, Chad E.; Zhang, Shen; Mendes, Wendy Berry
Three studies tested the hypothesis that negative metacognitive interpretations of anxious arousal under stereotype threat create cognitive deficits in intellectually threatening environments. Study 1 showed that among minority and White undergraduates, anxiety about an intelligence test predicted lower working memory when participants were primed with doubt as compared to confidence. Study 2 replicated this pattern with women and showed it to be unique to intellectually threatening environme...
Lusch, Bethany; Weholt, Jake; Maia, Pedro D; Kutz, J Nathan
The accurate diagnosis and assessment of neurodegenerative disease and traumatic brain injuries (TBI) remain open challenges. Both cause cognitive and functional deficits due to focal axonal swellings (FAS), but it is difficult to deliver a prognosis due to our limited ability to assess damaged neurons at a cellular level in vivo. We simulate the effects of neurodegenerative disease and TBI using convolutional neural networks (CNNs) as our model of cognition. We utilize biophysically relevant statistical data on FAS to damage the connections in CNNs in a functionally relevant way. We incorporate energy constraints on the brain by pruning the CNNs to be less over-engineered. Qualitatively, we demonstrate that damage leads to human-like mistakes. Our experiments also provide quantitative assessments of how accuracy is affected by various types and levels of damage. The deficit resulting from a fixed amount of damage greatly depends on which connections are randomly injured, providing intuition for why it is difficult to predict impairments. There is a large degree of subjectivity when it comes to interpreting cognitive deficits from complex systems such as the human brain. However, we provide important insight and a quantitative framework for disorders in which FAS are implicated. Copyright © 2018 Elsevier Inc. All rights reserved.
Oliver, Lindsay D; Mitchell, Derek G V; Dziobek, Isabel; MacKinley, Julia; Coleman, Kristy; Rankin, Katherine P; Finger, Elizabeth C
Behavioural variant frontotemporal dementia (bvFTD) is a debilitating neurodegenerative disorder characterized by frontal and temporal lobe atrophy primarily affecting social cognition and emotion, including loss of empathy. Many consider empathy to be a multidimensional construct, including cognitive empathy (the ability to adopt and understand another's perspective) and emotional empathy (the capacity to share another's emotional experience). Cognitive and emotional empathy deficits have been associated with bvFTD; however, little is known regarding the performance of patients with bvFTD on behavioural measures of emotional empathy, and whether empathic responses differ for negative versus positive stimuli. 24 patients with bvFTD and 24 healthy controls completed the Multifaceted Empathy Test (MET; Dziobek et al., 2008), a performance-based task that taps both cognitive and emotional facets of empathy, and allows for the discrimination of responses to negative versus positive realistic images. MET scores were also compared with caregiver ratings of patient behaviour on the Interpersonal Reactivity Index, which assesses patients' everyday demonstrations of perspective taking and empathic concern. Patients with bvFTD were less accurate than controls at inferring mental states for negative and positive stimuli. They also demonstrated lower levels of shared emotional experience, more positive emotional reactions, and diminished arousal to negative social stimuli relative to controls. Patients showed reduced emotional reactions to negative non-social stimuli as well. Lastly, the MET and IRI measures of emotional empathy were found to be significantly correlated within the bvFTD group. The results suggest that patients with bvFTD show a global deficit in cognitive empathy, and deficient emotional empathy for negative, but not positive, experiences. Further, a generalized emotional processing impairment for negative stimuli was observed, which could contribute to the
Dittrich, Winand H; Johansen, Thomas
The nature of cognitive deficits in obsessive-compulsive disorder (OCD) is characterized by contradictory findings in terms of specific neuropsychological deficits. Selective impairments have been suggested to involve visuospatial memory, set shifting, decision-making and response inhibition. The aim of this study was to investigate cognitive deficits in decision-making and executive functioning in OCD. It was hypothesized that the OCD patients would be less accurate in their responses compared to the healthy controls in rational decision-making on a version of the Cambridge gambling task (CGT) and on the color-word interference test and on a version of the Tower of Hanoi test (tower test) of executive functioning. Thirteen participants with OCD were compared to a group of healthy controls (n = 13) matched for age, gender, education and verbal IQ. Results revealed significant differences between the OCD group and the healthy control group on quality of decision-making on the CGT and for achievement score on the tower test. On these two tasks the OCD group performed worse than the healthy control group. The symptom-dimension analysis revealed performance differences where safety checking patients were impaired on the tower test compared to contamination patients. Results are discussed in the framework of cognition and emotion processing and findings implicate that OCD models should address, specifically, the interaction between cognition and emotion. Here the emotional disruption hypothesis is forwarded to account for the dysfunctional behaviors in OCD. Further implications regarding methodological and inhibitory factors affecting cognitive information processing are highlighted. © 2013 The Scandinavian Psychological Associations.
Riaan M. Olivier
Full Text Available Background: Thought disorder and visual-perceptual deficits have been well documented, but their relationships with clinical symptoms and cognitive function remain unclear. Cognitive-perceptual deficits may underscore clinical symptoms in schizophrenia patients. Aim: This study aimed to explore how thought disorder and form perception are related with clinical symptoms and cognitive dysfunction in first-episode schizophrenia. Setting: Forty-two patients with a first-episode of schizophrenia, schizophreniform or schizoaffective disorder were recruited from community clinics and state hospitals in the Cape Town area. Methods: Patients were assessed at baseline with the Rorschach Perceptual Thinking Index (PTI, the Positive and Negative Syndrome Scale (PANSS and the MATRICS Cognitive Consensus Battery (MCCB. Spearman correlational analyses were conducted to investigate relationships between PTI scores, PANSS factor analysis-derived domain scores and MCCB composite and subscale scores. Multiple regression models explored these relationships further. Results: Unexpectedly, poor form perception (X- % was inversely correlated with the severity of PANSS positive symptoms (r = -0.42, p = 0.02. Good form perception (XA% correlated significantly with speed of processing (r = 0.59, p < 0.01, working memory (r = 0.48, p < 0.01 and visual learning (r = 0.55, p < 0.01. PTI measures of thought disorder did not correlate significantly with PANSS symptom scores or cognitive performance. Conclusions: Form perception is associated with positive symptoms and impairment in executive function during acute psychosis. These findings suggest that there may be clinical value in including sensory-perceptual processing tasks in cognitive remediation and social cognitive training programmes for schizophrenia patients.
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.
Schulz, Kurt P; Bédard, Anne-Claude V; Fan, Jin; Clerkin, Suzanne M; Dima, Danai; 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 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.
Cortese, S.; Ferrin, M.; Brandeis, D.; Buitelaar, J.K.; Daley, D.; Dittmann, R.W.; Holtmann, M.; Santosh, P.; Stevenson, J.; Stringaris, A.; Zuddas, A.; Sonuga-Barke, E.J.
OBJECTIVE: The authors performed meta-analyses of randomized controlled trials to examine the effects of cognitive training on attention-deficit/hyperactivity disorder (ADHD) symptoms, neuropsychological deficits, and academic skills in children/adolescents with ADHD. METHOD: The authors searched
Morean, Diane F; O'Dwyer, Linda; Cherney, Leora R
To systematically review evidence of treatments for cognitive impairments experienced by at least 20% of all women who undergo chemotherapy for breast cancer. Searches of 5 databases (PubMed, Embase, Cochrane CENTRAL, PsycINFO, CINAHL), with no date or language restrictions, identified 1701 unique results. Search terms included breast cancer, chemotherapy, chemobrain, chemofog, and terms on cognition and language deficits. Included only peer-reviewed journal articles that described therapies for cognitive dysfunction in women undergoing (or who had undergone) chemotherapy for breast cancer and provided objective measurements of cognition or language. Data were extracted according to Cochrane recommendations, including characteristics of participants, interventions, outcomes, and studies. Quality assessment of all 12 eligible studies was performed using the Physiotherapy Evidence Database scale and treatment fidelity criteria. Screening, data extraction, and quality assessment reliability were performed. Six articles described interventions for cognition that took place during cancer treatment; 6, afterward. Five interventions were medical (including a strength-training program), 2 were restorative, and 5 were cognitive. Medicinal treatments were ineffective; restorative and exercise treatments had mixed results; cognitive therapy had success in varying cognitive domains. The domains most tested and most successfully treated were verbal memory, attention, and processing speed. Cognitive therapy protocols delivered after chemotherapy and aimed at improving verbal memory, attention, and processing speed hold the most promise. Future research is needed to clarify whether computerized cognitive training can be effective in treating this population, and to identify objective assessment tools that are sensitive to this disorder. Copyright © 2015 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.
Eliane Correa Miotto
Full Text Available Abstract Neuropsychological rehabilitation is related to the treatment or optimization of disabilities, handicaps and cognitive deficiencies including emotional, behavioral and personality alterations, aiming at the best cognitive, neurobiological and social re-adaptation. Objective: The main aim of this paper is to review scientific studies published over the last five years on cognitive training with rehabilitation, focusing on elderly subjects with cognitive complaints and patients diagnosed with MCI. Methods: Data were generated from Medline, PsychoInfo and EMBASE including publications from 2002 to 2007 using the search terms "Mild Cognitive Impairment", "Cognitive Complaints", "Rehabilitation" and "Intervention Studies". Data collection criteria were restricted to the quality of evidence Class I. Results: Eight articles out of sixty eight previously selected were chosen because of their randomized studies, including techniques of cognitive rehabilitation in patients with cognitive complaints, MCI and neuropsychological training. Conclusions: The studies showing generalization of rehabilitation techniques to practical real life situations and use of an errorless learning approach were considered more effective in terms of maintaining treatment follow up, although further studies are recommended.
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 Wilcoxon Exact Test was used to compare cognitive functioning test scores between completers and dropouts, and the Fisher Exact Test was used to compare proportion of negative urines between those with higher and lower scores on the cognitive tests. Marijuana abstinence was unrelated to cognitive functioning. However, dropouts scored significantly lower than completers on measures of abstract reasoning and processing accuracy, providing initial evidence that cognitive functioning plays a role in treatment retention of adult marijuana dependent patients. If supported by further studies, the findings may help inform the development of interventions tailored for cognitively impaired marijuana dependent patients. PMID:18329188
Fliss, Rafika; Lemerre, Marion; Mollard, Audrey
Compromised theory of mind (ToM) can be explained either by a failure to implement specific representational capacities (mental state representations) or by more general executive selection demands. In older adult populations, evidence supporting affected executive functioning and cognitive ToM in normal aging are reported. However, links between these two functions remain unclear. In the present paper, we address these shortcomings by using a specific task of ToM and classical executive tasks. We studied, using an original cognitive ToM task, the effect of age on ToM performances, in link with the progressive executive decline. 96 elderly participants were recruited. They were asked to perform a cognitive ToM task, and 5 executive tests (Stroop test and Hayling Sentence Completion Test to appreciate inhibitory process, Trail Making Test and Verbal Fluency for shifting assessment and backward span dedicated to estimate working memory capacity). The results show changes in cognitive ToM performance according to executive demands. Correlational studies indicate a significant relationship between ToM performance and the selected executive measures. Regression analyzes demonstrates that level of vocabulary and age as the best predictors of ToM performance. The results are consistent with the hypothesis that ToM deficits are related to age-related domain-general decline rather than as to a breakdown in specialized representational system. The implications of these findings for the nature of social cognition tests in normal aging are also discussed.
Calderón-Garcidueñas, Lilian; Mora-Tiscareño, Antonieta; Ontiveros, Esperanza; Gómez-Garza, Gilberto; Barragán-Mejía, Gerardo; Broadway, James; Chapman, Susan; Valencia-Salazar, Gildardo; Jewells, Valerie; Maronpot, Robert R; Henríquez-Roldán, Carlos; Pérez-Guillé, Beatriz; Torres-Jardón, Ricardo; Herrit, Lou; Brooks, Diane; Osnaya-Brizuela, Norma; Monroy, Maria E; González-Maciel, Angelica; Reynoso-Robles, Rafael; Villarreal-Calderon, Rafael; Solt, Anna C; Engle, Randall W
Exposure to air pollution is associated with neuroinflammation in healthy children and dogs in Mexico City. Comparative studies were carried out in healthy children and young dogs similarly exposed to ambient pollution in Mexico City. Children from Mexico City (n: 55) and a low polluted city (n:18) underwent psychometric testing and brain magnetic resonance imaging MRI. Seven healthy young dogs with similar exposure to Mexico City air pollution had brain MRI, measurement of mRNA abundance of two inflammatory genes cyclooxygenase-2, and interleukin 1 beta in target brain areas, and histopathological evaluation of brain tissue. Children with no known risk factors for neurological or cognitive disorders residing in a polluted urban environment exhibited significant deficits in a combination of fluid and crystallized cognition tasks. Fifty-six percent of Mexico City children tested showed prefrontal white matter hyperintense lesions and similar lesions were observed in dogs (57%). Exposed dogs had frontal lesions with vascular subcortical pathology associated with neuroinflammation, enlarged Virchow-Robin spaces, gliosis, and ultrafine particulate matter deposition. Based on the MRI findings, the prefrontal cortex was a target anatomical region in Mexico City children and its damage could have contributed to their cognitive dysfunction. The present work presents a groundbreaking, interdisciplinary methodology for addressing relationships between environmental pollution, structural brain alterations by MRI, and cognitive deficits/delays in healthy children.
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. Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics.
Mahati, K; Bhagya, V; Christofer, T; Sneha, A; Shankaranarayana Rao, B S
Severe depression compromises structural and functional integrity of the brain and results in impaired learning and memory, maladaptive synaptic plasticity as well as degenerative changes in the hippocampus and amygdala. The precise mechanisms underlying cognitive dysfunctions in depression remain largely unknown. On the other hand, enriched environment (EE) offers beneficial effects on cognitive functions, synaptic plasticity in the hippocampus. However, the effect of EE on endogenous depression associated cognitive dysfunction has not been explored. Accordingly, we have attempted to address this issue by investigating behavioural, structural and synaptic plasticity mechanisms in an animal model of endogenous depression after exposure to enriched environment. Our results demonstrate that depression is associated with impaired spatial learning and enhanced anxiety-like behaviour which is correlated with hypotrophy of the dentate gyrus and amygdalar hypertrophy. We also observed a gross reduction in the hippocampal long-term potentiation (LTP). We report a complete behavioural recovery with reduced indices of anhedonia and behavioural despair, reduced anxiety-like behaviour and improved spatial learning along with a complete restoration of dentate gyrus and amygdalar volumes in depressive rats subjected to EE. Enrichment also facilitated CA3-Schaffer collateral LTP. Our study convincingly proves that depression-induces learning deficits and impairs hippocampal synaptic plasticity. It also highlights the role of environmental stimuli in restoring depression-induced cognitive deficits which might prove vital in outlining more effective strategies to treat major depressive disorders. Copyright © 2016 Elsevier Inc. All rights reserved.
Full Text Available Exposure to adverse early-life events is thought to be the risk factors for the development of psychiatric and altered cognitive function in adulthood. The purpose of this study was to investigate whether electroacupuncture (EA treatment in young adult rat would improve impaired cognitive function and synaptic plasticity in adult rat with neonatal maternal separation (MS. Wistar rats were randomly divided into four groups: control group, MS group, MS with EA treatment (MS + EA group, and MS with Sham-EA treatment (MS + Sham-EA group. We evaluated the cognitive function by using Morris water maze and fear conditioning tests. Electrophysiology experiment used in vivo long-term potentiation (LTP at Schaffer Collateral-CA1 synapses was detected to assess extent of synaptic plasticity. Repeated EA stimulation at Baihui (GV 20 and Yintang (GV 29 during postnatal 9 to 11 weeks was identified to significantly ameliorate poor performance in behavior tests and improve the impaired LTP induction detected at Schaffer Collateral-CA1 synapse in hippocampus. Collectively, the findings suggested that early-life stress due to MS may induce adult cognitive deficit associated with hippocampus, and EA in young adult demonstrated that its therapeutic efficacy may be via ameliorating deficit of hippocampal synaptic plasticity.
Lecardeur, L; Meunier-Cussac, S; Dollfus, S
Up to now, studies have not demonstrated significant efficacy of antipsychotics on cognitive impairments in patients with psychotic disorders. These cognitive deficits are of particular interest since they traditionally start early before the diagnosis of psychosis. They are observed during premorbid and prodromal stages, and during the first episode of psychosis. Moreover, cognitive impairments may be detected without any psychotic symptoms (such as positive symptoms) suggesting their development independently of the psychotic symptoms. Cognitive disturbances consist of impairments of episodic and working memories, intellectual functioning, executive functions (planning, inhibition, and cognitive flexibility), selective and sustained attentions and social cognition (emotion, recognition, theory of mind). The altered cognitive functions observed in schizophrenia are the same as in earlier stages but at a lower level of severity. Data suggest that cognitive deficits can be considered as vulnerability markers of psychosis since they have been described in healthy relatives of psychotic patients with high genetic risk. Cognitive deficits might also be considered as predictive of the occurrence of the disease after the first episode of psychosis. Indeed, retrospective studies suggest cognitive impairments in patients with schizophrenia during premorbid and prodromal phases but not in bipolar patients. Cognitive assessment might be of particular interest in people at risk for psychosis, in order to differentiate diagnostic outcomes. Cognitive functioning impairs until the diagnosis of first episode psychosis, even though cognitive profiles are quite heterogeneous in these patients. Once the diagnosis of schizophrenia is considered, cognitive deficits may be stable, although the literature is still controversial. Several factors such as symptoms and gender can contribute in diversifying the cognitive profiles. Moreover, age of onset might worsen the prognosis because of
Paulo T, R S; Tribess, Sheilla; Sasaki, Jeffer Eidi; Meneguci, Joilson; Martins, Cristiane A; Freitas, Ismael F; Romo-Perez, Vicente; Virtuoso, Jair S
The aim of this study was to examine the association of physical activity with depression and cognition deficit, separately and combined, in Brazilian older adults. We analyzed data from 622 older adults. Physical activity was assessed using the International Physical Activity Questionnaire. Depressive symptoms were assessed using the Geriatric Depression Scale, while cognitive deficit was assessed using the Mini-Mental State Examination. Multinomial logistic regressions were used to assess associations of depression and cognitive deficit with sociodemographic, health, and behavioral variables. Prevalence of physical inactivity (physical activity/ week), depression, and cognitive deficit were 35.7%, 37.4%, and 16.7%. Physical inactivity was associated with depression (OR: 1.83, 95% CI: 1.14-2.94) and with depression and cognitive deficit combined (OR: 4.23, 95% CI: 2.01-8.91). Physically inactive participants were also more likely to present limitations in orientation and language functions. Physical inactivity was associated with depression and also with depression and cognitive deficit combined in older adults.
Swanson, James; Baler, Ruben D; Volkow, Nora D
The use of stimulant drugs for the treatment of children with attention-deficit hyperactivity disorder (ADHD) is one of the most widespread pharmacological interventions in child psychiatry and behavioral pediatrics. This treatment is well grounded on controlled studies showing efficacy of low oral doses of methylphenidate and amphetamine in reducing the behavioral symptoms of the disorder as reported by parents and teachers, both for the cognitive (inattention and impulsivity) and non-cognitive (hyperactivity) domains. Our main aim is to review the objectively measured cognitive effects that accompany the subjectively assessed clinical responses to stimulant medications. Recently, methods from the cognitive neurosciences have been used to provide information about brain processes that underlie the cognitive deficits of ADHD and the cognitive effects of stimulant medications. We will review some key findings from the recent literature, and then offer interpretations of the progress that has been made over the past decade in understanding the cognitive effects of stimulant medication on individuals with ADHD.
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.
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.
Molina, Vicente; Bachiller, Alejandro; Gomez-Pilar, Javier; Lubeiro, Alba; Hornero, Roberto; Cea-Cañas, Benjamín; Valcárcel, César; Haidar, Mahmoun-Karim; Poza, Jesús
Spectral entropy (SE) is a measurement from information theory field that provides an estimation of EEG regularity and may be useful as a summary of its spectral properties. Previous studies using small samples reported a deficit of EEG entropy modulation in schizophrenia during cognitive activity. The present study is aimed at replicating this finding in a larger sample, to explore its cognitive and clinical correlates and to discard antipsychotic treatment as the main source of that deficit. We included 64 schizophrenia patients (21 first episodes, FE) and 65 healthy controls. We computed SE during performance of an odd-ball paradigm, at the windows prior (-300 to 0ms) and following (150 to 450ms) stimulus presentation. Modulation of SE was defined as the difference between post- and pre-stimulus windows. In comparison to controls, patients showed a deficit of SE modulation over frontal and central regions, also shown by FE patients. Baseline SE did not differ between patients and controls. Modulation deficit was directly associated with cognitive deficits and negative symptoms, and inversely with positive symptoms. SE modulation was not related to antipsychotic doses. Patients also showed a smaller change of median frequency (i.e., smaller slowing of oscillatory activity) of the EEG from pre- to post-stimulus windows. These results support that a deficit of fast modulation contributes to cognitive deficits and symptoms in schizophrenia patients. Copyright © 2017. Published by Elsevier B.V.
Avtzon, Sarah Abitbol
Working memory, executive functions, and cognitive processes associated with specific academic areas, are empirically identified as being the core underlying cognitive deficits in students with specific learning disabilities. Using Hebb's theory of neuroplasticity and the principle of automaticity as theoretical bases, this experimental study…
Full Text Available This review focuses on the cognitive neuroscience of Attention Deficit Hyperactivity Disorder (ADHD based on functional magnetic resonance imaging (fMRI studies and on recent clinically relevant applications such as fMRI-based diagnostic classification or neuromodulation therapies targeting fMRI deficits with neurofeedback (NF or brain stimulation. Meta-analyses of fMRI studies of executive functions (EFs show that ADHD patients have cognitive-domain dissociated complex multisystem impairments in several right and left hemispheric dorsal, ventral and medial fronto-cingulo-striato-thalamic and fronto-parieto-cerebellar networks that mediate cognitive control, attention, timing and working memory (WM. There is furthermore emerging evidence for abnormalities in orbital and ventromedial prefrontal and limbic areas that mediate motivation and emotion control. In addition, poor deactivation of the default mode network (DMN suggests an abnormal interrelationship between hypo-engaged task-positive and poorly “switched off” hyper-engaged task-negative networks, both of which are related to impaired cognition. Translational cognitive neuroscience in ADHD is still in its infancy. Pattern recognition analyses have attempted to provide diagnostic classification of ADHD using fMRI data with respectable classification accuracies of over 80%. Necessary replication studies, however, are still outstanding. Brain stimulation has been tested in heterogeneously designed, small numbered proof of concept studies targeting key frontal functional impairments in ADHD. Transcranial direct current stimulation (tDCS appears to be promising to improve ADHD symptoms and cognitive functions based on some studies, but larger clinical trials of repeated stimulation with and without cognitive training are needed to test clinical efficacy and potential costs on non-targeted functions. Only three studies have piloted NF of fMRI-based frontal dysfunctions in ADHD using fMRI or
This review focuses on the cognitive neuroscience of Attention Deficit Hyperactivity Disorder (ADHD) based on functional magnetic resonance imaging (fMRI) studies and on recent clinically relevant applications such as fMRI-based diagnostic classification or neuromodulation therapies targeting fMRI deficits with neurofeedback (NF) or brain stimulation. Meta-analyses of fMRI studies of executive functions (EFs) show that ADHD patients have cognitive-domain dissociated complex multisystem impairments in several right and left hemispheric dorsal, ventral and medial fronto-cingulo-striato-thalamic and fronto-parieto-cerebellar networks that mediate cognitive control, attention, timing and working memory (WM). There is furthermore emerging evidence for abnormalities in orbital and ventromedial prefrontal and limbic areas that mediate motivation and emotion control. In addition, poor deactivation of the default mode network (DMN) suggests an abnormal interrelationship between hypo-engaged task-positive and poorly “switched off” hyper-engaged task-negative networks, both of which are related to impaired cognition. Translational cognitive neuroscience in ADHD is still in its infancy. Pattern recognition analyses have attempted to provide diagnostic classification of ADHD using fMRI data with respectable classification accuracies of over 80%. Necessary replication studies, however, are still outstanding. Brain stimulation has been tested in heterogeneously designed, small numbered proof of concept studies targeting key frontal functional impairments in ADHD. Transcranial direct current stimulation (tDCS) appears to be promising to improve ADHD symptoms and cognitive functions based on some studies, but larger clinical trials of repeated stimulation with and without cognitive training are needed to test clinical efficacy and potential costs on non-targeted functions. Only three studies have piloted NF of fMRI-based frontal dysfunctions in ADHD using fMRI or near
Maria Luz eGonzalez-Gadea
Full Text Available Emotion recognition and empathy abilities require the integration of contextual information in real-life scenarios. Previous reports have explored these domains in adolescent offenders (AOs but have not used tasks that replicate everyday situations. In this study we included ecological measures with different levels of contextual dependence to evaluate emotion recognition and empathy in AOs relative to non-offenders, controlling for the effect of demographic variables. We also explored the influence of fluid intelligence (FI and executive functions (EFs in the prediction of relevant deficits in these domains. Our results showed that AOs exhibit deficits in context-sensitive measures of emotion recognition and cognitive empathy. Difficulties in these tasks were neither explained by demographic variables nor predicted by FI or EFs. However, performance on measures that included simpler stimuli or could be solved by explicit knowledge was either only partially affected by demographic variables or preserved in AOs. These findings indicate that AOs show contextual social-cognition impairments which are relatively independent of basic cognitive functioning and demographic variables.
Alex C Bender
Full Text Available Brain oscillations play a critical role in information processing and may, therefore, be essential to uncovering the mechanisms of cognitive impairment in neurological disease. In Dravet syndrome (DS, a mutation in SCN1A, coding for the voltage-gated sodium channel Nav1.1, is associated with severe cognitive impairment and seizures. While seizure frequency and severity do not correlate with the extent of impairment, the slowing of brain rhythms may be involved. Here we investigate the role of Nav1.1 on brain rhythms and cognition using RNA interference. We demonstrate that knockdown of Nav1.1 impairs fast- and burst-firing properties of neurons in the medial septum in vivo. The proportion of neurons that fired phase-locked to hippocampal theta oscillations was reduced, and medial septal regulation of theta rhythm was disrupted. During a working memory task, this deficit was characterized by a decrease in theta frequency and was negatively correlated with performance. These findings suggest a fundamental role for Nav1.1 in facilitating fast-firing properties in neurons, highlight the importance of precise temporal control of theta frequency for working memory, and imply that Nav1.1 deficits may disrupt information processing in DS via a dysregulation of brain rhythms.
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.
Tsutsumimoto, Kota; Doi, Takehiko; Makizako, Hyuma; Hotta, Ryo; Nakakubo, Sho; Makino, Keitaro; Suzuki, Takao; Shimada, Hiroyuki
Our objective was to investigate the association between social frailty and cognitive and physical function among older adults. This was a cross-sectional study. We examined community-dwelling adults in Japan. Participants comprised 4425 older Japanese people from the National Center for Geriatrics and Gerontology-Study of Geriatric Syndromes. Social frailty was defined by using responses to 5 questions (going out less frequently, rarely visiting friends, feeling unhelpful to friends or family, living alone, and not talking with someone every day). Participants showing none of these components were considered nonfrail; those showing 1 component were considered prefrail; and those showing 2 or more components were considered frail. To screen for cognitive deficits, we assessed memory, attention, executive function, and processing speed. Having 2 or more tests with age-adjusted scores of at least 1.5 standard deviations below the reference threshold was sufficient to be characterized as cognitively deficient. To screen for physical function deficits, we assessed walking speed (physically deficient. The prevalence of social frailty was the following: nonfrailty, 64.1% (N = 2835); social prefrailty, 24.8% (N = 1097); social frailty, 11.1% (N = 493; P for trend physical function (gait speed and grip strength) also varied between social frailty groups (all Ps for trend physical function (odds ratio = 1.99, 95% confidence interval 1.57-2.52) after adjusting for covariates. This study revealed that social frailty is associated with both cognitive and physical function among Japanese older adults. And social frailty status was also negatively associated with physical function. Further studies are needed to elucidate if a casual association exists between social frailty and cognitive and physical function. Copyright © 2017 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.
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.
Full Text Available Background: Child development is a very important phase, which children learn various skills as future generations in the future. Disorders that can impede child development process of Attention Deficit Hyperactivity Disorder (ADHD. Children with ADHD have problems with cognitive abilities, of which about 20-60% of them have learning disorders. The efforts to support cognitive development in ADHD children is to approach the child's environment through parenting parents. Objective: This study aimed to determine the correlation of parenting style with cognitive development in the children with ADHD in SLB Negeri 1 Denpasar. Methods: This study used correlational design with cross sectional approach. The sample size of 30 respondents were taken by purposive sampling technique. Data were collected using parenting style questionnaire (PSQ and the average value of odd semester report of 2016/2017 academic year. Results: The result of this research was found that most parents with democratic parenting type were 19 people (63.3%, authoritarian parenting type were 7 people (23.3% and permissive parenting were 4 people (13.3%. The result of contingency coefficient test with p-value = 0.039 (p <0.05 and correlation value of 0.501, which mean there was high correlation between parenting style with cognitive development in children with ADHD. Conclusion: It is suggested for parents with ADHD children to be able to provide good parenting for the child's development, especially for the child's cognitive development.
Roels, H A; Bowler, R M; Kim, Y; Claus Henn, B; Mergler, D; Hoet, P; Gocheva, V V; Bellinger, D C; Wright, R O; Harris, M G; Chang, Y; Bouchard, M F; Riojas-Rodriguez, H; Menezes-Filho, J A; Téllez-Rojo, Martha Maria
This symposium comprised five oral presentations dealing with recent findings on Mn-related cognitive and motor changes from epidemiological studies across the life span. The first contribution highlighted the usefulness of functional neuroimaging of the central nervous system (CNS) to evaluate cognitive as well as motor deficits in Mn-exposed welders. The second dealt with results of two prospective studies in Mn-exposed workers or welders showing that after decrease of Mn exposure the outcome of reversibility in adverse CNS effects may differ for motor and cognitive function and, in addition the issue of plasma Mn as a reliable biomarker for Mn exposure in welders has been addressed. The third presentation showed a brief overview of the results of an ongoing study assessing the relationship between environmental airborne Mn exposure and neurological or neuropsychological effects in adult Ohio residents living near a Mn point source. The fourth paper focused on the association between blood Mn and neurodevelopment in early childhood which seems to be sensitive to both low and high Mn concentrations. The fifth contribution gave an overview of six studies indicating a negative impact of excess environmental Mn exposure from air and drinking water on children's cognitive performance, with special attention to hair Mn as a potential biomarker of exposure. These studies highlight a series of questions about Mn neurotoxicity with respect to cognitive processes, forms and routes of exposure, adequate biomarkers of exposure, gender differences, susceptibility and exposure limits with regard to age. Copyright © 2012 Elsevier Inc. All rights reserved.
Ogawa, Tomohiro; Tanaka, Hideaki; Hirata, Koichi
To determine the cognitive profiles in non-demented, relatively less handicapped patients with early-stage sporadic amyotrophic lateral sclerosis (ALS) by using neuropsychological tests, event-related potentials (ERPs) and clinical scale. We recruited 19 patients with sporadic ALS (eight with limb-onset, 11 with bulbar-onset) and 19 controls. In addition to the mini-mental state examination and the Wechsler adult intelligence scale-revised, we assessed the frontal lobe function with Wisconsin card sorting test, Stroop test and trail making test. We used auditory 'oddball' counting paradigm for the ERPs under 20-channel electroencephalogram (EEG) recording. Global field power (GFP) was computed, and its peak amplitudes and latencies of N1/N2/P3 were determined. The results of ERP and neuropsychological tests were correlated with respiratory function and clinical scale. No global cognitive impairment except for subtle frontal dysfunction was detected, although N1/N2/P3 GFP latencies were significantly prolonged in ALS patients than in the controls. Vital capacity correlated with P3 GFP amplitude, and the relative bulbar functional rating scale correlated with P3 GFP latency. Our findings indicated the presence of sub-clinical cognitive deficits in non-demented, sporadic ALS patients. In addition, clinical sub-types and respiratory function dependently influenced cognitive function in patients with sporadic ALS. ERP confirmed cognitive impairment in patients with sporadic ALS.
Xian, Yan-Fang; Lin, Zhi-Xiu; Zhao, Ming; Mao, Qing-Qiu; Ip, Siu-Po; Che, Chun-Tao
The stem with hooks of Uncaria rhynchophylla is a component herb of many traditional formulae for the treatment of neurodegenerative diseases. However, scientific evidence of the efficacy of Uncaria rhynchophylla in the treatment of Alzheimer's disease (AD) in animal models is lacking. Thus, in the present study, we investigated whether the 70 % aqueous ethanol extract of Uncaria rhynchophylla (EUR) could protect against D-galactose (D-gal)-induced cognitive deficits in mice. Mice were given a subcutaneous injection of D-gal (50 mg/kg) and orally administered EUR (100, 200, or 400 mg/kg) daily for 8 weeks. The effect of EUR on D-gal-induced cognitive deficits was evaluated by measuring behavioral and neurochemical parameters of AD and the antioxidant status of brain tissue. The results showed that EUR (200 or 400 mg/kg) significantly increased exploratory behavior (assessed by an open-field test) and improved spatial learning and memory function (assessed by the Morris water maze test) in D-gal-treated mice. In addition, EUR (200 or 400 mg/kg) significantly increased the levels of acetylcholine and glutathione and decreased the activity of acetylcholinesterase and the level of malondialdehyde in the brains of D-gal-treated mice. These results indicate that EUR ameliorates cognitive deficits induced by D-gal in mice, and that this action may be mediated, at least in part, by the inhibition of acetylcholinesterase activity and the enhancement of the antioxidant status of brain tissue. © Georg Thieme Verlag KG Stuttgart · New York.
Jekel, Katrin; Damian, Marinella; Wattmo, Carina; Hausner, Lucrezia; Bullock, Roger; Connelly, Peter J; Dubois, Bruno; Eriksdotter, Maria; Ewers, Michael; Graessel, Elmar; Kramberger, Milica G; Law, Emma; Mecocci, Patrizia; Molinuevo, José L; Nygård, Louise; Olde-Rikkert, Marcel Gm; Orgogozo, Jean-Marc; Pasquier, Florence; Peres, Karine; Salmon, Eric; Sikkes, Sietske Am; Sobow, Tomasz; Spiegel, René; Tsolaki, Magda; Winblad, Bengt; Frölich, Lutz
There is a growing body of evidence that subtle deficits in instrumental activities of daily living (IADL) may be present in mild cognitive impairment (MCI). However, it is not clear if there are IADL domains that are consistently affected across patients with MCI. In this systematic review, therefore, we aimed to summarize research results regarding the performance of MCI patients in specific IADL (sub)domains compared with persons who are cognitively normal and/or patients with dementia. The databases PsycINFO, PubMed and Web of Science were searched for relevant literature in December 2013. Publications from 1999 onward were considered for inclusion. Altogether, 497 articles were retrieved. Reference lists of selected articles were searched for potentially relevant articles. After screening the abstracts of these 497 articles, 37 articles were included in this review. In 35 studies, IADL deficits (such as problems with medication intake, telephone use, keeping appointments, finding things at home and using everyday technology) were documented in patients with MCI. Financial capacity in patients with MCI was affected in the majority of studies. Effect sizes for group differences between patients with MCI and healthy controls were predominantly moderate to large. Performance-based instruments showed slight advantages (in terms of effect sizes) in detecting group differences in IADL functioning between patients with MCI, patients with Alzheimer's disease and healthy controls. IADL requiring higher neuropsychological functioning seem to be most severely affected in patients with MCI. A reliable identification of such deficits is necessary, as patients with MCI with IADL deficits seem to have a higher risk of converting to dementia than patients with MCI without IADL deficits. The use of assessment tools specifically designed and validated for patients with MCI is therefore strongly recommended. Furthermore, the development of performance-based assessment instruments
Full Text Available Yeon-Jeong Shin,1,2 Yo-Han Joo,1 Jong-Hoon Kim1–3 1Neuroscience Research Institute, 2Department of Health Sciences and Technology, Gachon Advanced Institute for Health Sciences & Technology, 3Department of Psychiatry, Gil Medical Center, Gachon University School of Medicine, Gachon University, Incheon, Republic of Korea Background: We investigated self-perceived cognitive deficits and their relationship with internalized stigma and quality of life in patients with schizophrenia in order to shed light on the clinical correlates of subjective cognitive deficits in schizophrenia.Methods: Seventy outpatients with schizophrenia were evaluated. Patients’ self-perceived cognitive deficits, internalized stigma, and subjective quality of life were assessed using the Scale to Investigate Cognition in Schizophrenia (SSTICS, the Internalized Stigma of Mental Illness Scale (ISMI, and the Schizophrenia Quality of Life Scale Revision 4 (SQLS-R4, respectively. Correlation and regression analyses controlling for the severity of symptoms of schizophrenia were performed, and a mediation analysis was conducted to examine the hypothesis that internalized stigma mediates the relationship between self-perceived cognitive deficits and subjective quality of life.Results: Pearson’s partial correlation analysis showed significant correlations among the SSTICS, ISMI, and SQLS-R4 scores (P<0.01. Multiple regression analysis showed that the SSTICS and ISMI scores significantly predicted the SQLS-R4 score (P<0.01. Mediation analysis revealed that the strength of the association between the SSTICS and SQLS-R4 scores decreased from β=0.74 (P<0.01 to β=0.56 (P<0.01, when the ISMI score was statistically controlled. The Sobel test revealed that this difference was significant (P<0.01, indicating that internalized stigma partially mediated the relationship between self-perceived cognitive deficits and quality of life.Conclusion: The present study indicates that self
Frajo-Apor, Beatrice; Pardeller, Silvia; Kemmler, Georg; Welte, Anna-Sophia; Hofer, Alex
Previous studies using the Mayer-Salovey-Caruso Emotional Intelligence Test (MSCEIT) revealed significant performance deficits across all areas of Emotional Intelligence (EI) in schizophrenia patients compared to healthy controls. However, none of these studies has investigated a potential influence of non-social cognition on these findings. 56 schizophrenia outpatients and 84 control subjects were investigated using the MSCEIT and the Brief Assessment of Cognition in Schizophrenia (BACS). Analyses of covariance were performed with adjustment for the BACS composite score and education. To investigate this issue in more detail, a mediation analysis was conducted. Patients showed significantly lower EI and non-social cognition levels compared to healthy controls. After adjustment for BACS composite score and education, only the group difference in the "managing emotions" branch and thus in the "strategic" EI part of the MSCEIT remained statistically significant, whereas for all other MSCEIT branches (perceiving, using, understanding emotions) statistical significance was lost. The mediation analysis revealed that the difference between schizophrenia patients and controls regarding the MSCEIT total score was almost fully attributable to the mediating effect of non-social cognition. Our findings suggest that in schizophrenia patients EI is largely influenced by non-social cognitive functioning. Only the "managing emotions" branch was found to be independent of non-social cognition. Consequently, non-social cognitive performance was mainly responsible for the observed differences in EI between schizophrenia patients and controls. This has to be taken into account when interpreting MSCEIT data in this population. Copyright © 2016 Elsevier B.V. All rights reserved.
Full Text Available 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. Methods Sixty-five children (32 male, mean 8.4 years, SD 3.0 years aged between 4-15 years with a history of PM and an age-matched control group of 93 children (46 male; mean 8.4 years, SD 2.7 years were recruited from a well-demarcated study area in Kilifi. In the present study, both baseline to peak and peak-to-peak amplitude differences are reported. Results Children with a history of pneumococcal meningitis had significantly longer auditory P1 and P3a latencies and smaller P1 amplitudes compared to unexposed children. In the visual paradigm, children with PM seemingly lacked a novelty P3a component around 350 ms where control children had a maximum, and showed a lack of stimulus differentiation at Nc. Further, children with exposure to PM had smaller peak to peak amplitude (N2-P1 compared to unexposed children. Conclusion The results suggest that children with a history of PM process novelty differently than do unexposed children, with slower latencies and reduced or absent components. This pattern suggests poorer auditory attention and/or cognitive slowness and poorer visual attention orienting, possibly due to disruption in the functions of the lateral prefrontal and superior temporal cortices. ERPs may be useful for assessment of the development of perceptual-cognitive functions in post brain-injury in African children by providing an alternate way of assessing cognitive development in patient groups for whom more typical standardized neuropsychological
Schmader, Toni; Forbes, Chad E; Zhang, Shen; Mendes, Wendy Berry
Three studies tested the hypothesis that negative metacognitive interpretations of anxious arousal under stereotype threat create cognitive deficits in intellectually threatening environments. Study 1 showed that among minority and White undergraduates, anxiety about an intelligence test predicted lower working memory when participants were primed with doubt as compared to confidence. Study 2 replicated this pattern with women and showed it to be unique to intellectually threatening environments. Study 3 used emotional reappraisal as an individual difference measure of the tendency to metacognitively reinterpret negative emotions and found that when sympathetic activation was high (indexed by salivary alpha-amylase), women who tended to reappraise negative feelings performed better in math and felt less self-doubt than those low in reappraisal. Overall, findings highlight how metacognitive interpretations of affect can undermine cognitive efficiency under stereotype threat and offer implications for the situational and individual difference variables that buffer people from these effects.
Rui, Xu; Wenfang, Li; Jing, Cheng; Meng, Chen; Chengcheng, Ding; Jiqu, Xu; Shuang, Rong
Accumulating epidemiological and experimental studies have confirmed that a high-cholesterol diet is detrimental to cognitive performance in animal models. Phytosterols, a class of naturally occurring structural components in plant foods, have been demonstrated to possess cholesterol-lowering and antioxidant effects. Phytosterol esters (PSE) are esters of phytosterol. The aim of this study was to evaluate the neuroprotective effects of PSE on cognitive deficit induced by a cholesterol-enriched diet in aged rats, and to explore their underlying mechanisms for these effects. Based on their Morris water maze performance, the latencies differed by <1.5 standard deviations (SDs) on days 3-5 of testing, 60 rats were chosen from 12-month-old female Sprague Dawley aged rats and were randomized into three groups, which were fed either a control diet, a high cholesterol diet (HCD) or a high-cholesterol diet supplemented with 2% PSE (HCD + PSE) for 6 months. In our study, we found that PSE treatment maintained the body weight balance, reduced the serum lipid levels, and improved the cognitive performance of aged rats in the Morris water maze test, as evaluated by shortened escape latencies. Importantly, histological and immunohistochemical results in the brain showed that PSE supplementation may have a neuroprotective effect that alleviates neuroinflammation in aged rats. This neuroprotective effect significantly inhibited degeneration, resulting in a significant increase in the number of pyramidal cells and an apparent decrease in the number of astrocytes compared to rats that were fed only a HCD. Furthermore, PSE improved cholinergic activities by restoring the acetylcholine (ACh) content and decreasing acetylcholinesterase (AChE) activity in the cerebral cortex, as well as by elevating choline acetyl transferase (ChAT) activity in the hippocampus and the cerebral cortex. These results suggest that PSE can play a useful role in alleviating cognitive deficit induced by a
Fjalldal, S; Follin, C; Svärd, D; Rylander, L; Gabery, S; Petersén, Å; van Westen, D; Sundgren, P C; Björkman-Burtscher, I M; Lätt, J; Ekman, B; Johanson, A; Erfurth, E M
Patients with craniopharyngioma (CP) and hypothalamic lesions (HL) have cognitive deficits. Which neural pathways are affected is unknown. To determine whether there is a relationship between microstructural white matter (WM) alterations detected with diffusion tensor imaging (DTI) and cognition in adults with childhood-onset CP. A cross-sectional study with a median follow-up time of 22 (6-49) years after operation. The South Medical Region of Sweden (2.5 million inhabitants). Included were 41 patients (24 women, ≥17 years) surgically treated for childhood-onset CP between 1958-2010 and 32 controls with similar age and gender distributions. HL was found in 23 patients. Subjects performed cognitive tests and magnetic resonance imaging, and images were analyzed using DTI of uncinate fasciculus, fornix, cingulum, hippocampus and hypothalamus as well as hippocampal volumetry. Right uncinate fasciculus was significantly altered ( P ≤ 0.01). Microstructural WM alterations in left ventral cingulum were significantly associated with worse performance in visual episodic memory, explaining approximately 50% of the variation. Alterations in dorsal cingulum were associated with worse performance in immediate, delayed recall and recognition, explaining 26-38% of the variation, and with visuospatial ability and executive function, explaining 19-29%. Patients who had smaller hippocampal volume had worse general knowledge ( P = 0.028), and microstructural WM alterations in hippocampus were associated with a decline in general knowledge and episodic visual memory. A structure to function relationship is suggested between microstructural WM alterations in cingulum and in hippocampus with cognitive deficits in CP. © 2018 The authors.
Stampanoni Bassi, Mario; Garofalo, Sara; Marfia, Girolama A; Gilio, Luana; Simonelli, Ilaria; Finardi, Annamaria; Furlan, Roberto; Sancesario, Giulia M; Di Giandomenico, Jonny; Storto, Marianna; Mori, Francesco; Centonze, Diego; Iezzi, Ennio
Cognitive deficits are frequently observed in multiple sclerosis (MS), mainly involving processing speed and episodic memory. Both demyelination and gray matter atrophy can contribute to cognitive deficits in MS. In recent years, neuroinflammation is emerging as a new factor influencing clinical course in MS. Inflammatory cytokines induce synaptic dysfunction in MS. Synaptic plasticity occurring within hippocampal structures is considered as one of the basic physiological mechanisms of learning and memory. In experimental models of MS, hippocampal plasticity is profoundly altered by proinflammatory cytokines. Although mechanisms of inflammation-induced hippocampal pathology in MS are not completely understood, alteration of Amyloid-β (Aβ) metabolism is emerging as a key factor linking together inflammation, synaptic plasticity and neurodegeneration in different neurological diseases. We explored the correlation between concentrations of Aβ 1-42 and the levels of some proinflammatory and anti-inflammatory cytokines (interleukin-1β (IL-1β), IL1-ra, IL-8, IL-10, IL-12, tumor necrosis factor α (TNFα), interferon γ (IFNγ)) in the cerebrospinal fluid (CSF) of 103 remitting MS patients. CSF levels of Aβ 1-42 were negatively correlated with the proinflammatory cytokine IL-8 and positively correlated with the anti-inflammatory molecules IL-10 and interleukin-1 receptor antagonist (IL-1ra). Other correlations, although noticeable, were either borderline or not significant. Our data show that an imbalance between proinflammatory and anti-inflammatory cytokines may lead to altered Aβ homeostasis, representing a key factor linking together inflammation, synaptic plasticity and cognitive dysfunction in MS. This could be relevant to identify novel therapeutic approaches to hinder the progression of cognitive dysfunction in MS.
Mario Stampanoni Bassi
Full Text Available Cognitive deficits are frequently observed in multiple sclerosis (MS, mainly involving processing speed and episodic memory. Both demyelination and gray matter atrophy can contribute to cognitive deficits in MS. In recent years, neuroinflammation is emerging as a new factor influencing clinical course in MS. Inflammatory cytokines induce synaptic dysfunction in MS. Synaptic plasticity occurring within hippocampal structures is considered as one of the basic physiological mechanisms of learning and memory. In experimental models of MS, hippocampal plasticity is profoundly altered by proinflammatory cytokines. Although mechanisms of inflammation-induced hippocampal pathology in MS are not completely understood, alteration of Amyloid-β (Aβ metabolism is emerging as a key factor linking together inflammation, synaptic plasticity and neurodegeneration in different neurological diseases. We explored the correlation between concentrations of Aβ1–42 and the levels of some proinflammatory and anti-inflammatory cytokines (interleukin-1β (IL-1β, IL1-ra, IL-8, IL-10, IL-12, tumor necrosis factor α (TNFα, interferon γ (IFNγ in the cerebrospinal fluid (CSF of 103 remitting MS patients. CSF levels of Aβ1–42 were negatively correlated with the proinflammatory cytokine IL-8 and positively correlated with the anti-inflammatory molecules IL-10 and interleukin-1 receptor antagonist (IL-1ra. Other correlations, although noticeable, were either borderline or not significant. Our data show that an imbalance between proinflammatory and anti-inflammatory cytokines may lead to altered Aβ homeostasis, representing a key factor linking together inflammation, synaptic plasticity and cognitive dysfunction in MS. This could be relevant to identify novel therapeutic approaches to hinder the progression of cognitive dysfunction in MS.
Wang, Xiao-Dong; Rammes, Gerhard; Kraev, Igor; Wolf, Miriam; Liebl, Claudia; Scharf, Sebastian H.; Rice, Courtney J.; Wurst, Wolfgang; Holsboer, Florian; Deussing, Jan M.; Baram, Tallie Z.; Stewart, Michael G.; Müller, Marianne B.; Schmidt, Mathias V.
Childhood traumatic events hamper the development of the hippocampus and impair declarative memory in susceptible individuals. Persistent elevations of hippocampal corticotropin-releasing factor (CRF), acting through CRF receptor 1 (CRF1), in experimental models of early-life stress have suggested a role for this endogenous stress hormone in the resulting structural modifications and cognitive dysfunction. However, direct testing of this possibility has been difficult. In the current study, we subjected conditional forebrain CRF1 knock-out (CRF1-CKO) mice to an impoverished postnatal environment and examined the role of forebrain CRF1 in the long-lasting effects of early-life stress on learning and memory. Early-life stress impaired spatial learning and memory in wild-type mice, and postnatal forebrain CRF overexpression reproduced these deleterious effects. Cognitive deficits in stressed wild-type mice were associated with disrupted long-term potentiation (LTP) and a reduced number of dendritic spines in area CA3 but not in CA1. Forebrain CRF1 deficiency restored cognitive function, LTP and spine density in area CA3, and augmented CA1 LTP and spine density in stressed mice. In addition, early-life stress differentially regulated the amount of hippocampal excitatory and inhibitory synapses in wild-type and CRF1-CKO mice, accompanied by alterations in the neurexin-neuroligin complex. These data suggest that the functional, structural and molecular changes evoked by early-life stress are at least partly dependent on persistent forebrain CRF1 signaling, providing a molecular target for the prevention of cognitive deficits in adults with a history of early-life adversity. PMID:21940453
Hulka, Lea M; Wagner, Michael; Preller, Katrin H; Jenni, Daniela; Quednow, Boris B
Specific blue-yellow colour vision impairment has been reported in dependent cocaine users and it was postulated that drug-induced changes in retinal dopamine neurotransmission are responsible. However, it is unclear whether these changes are confined to chronic cocaine users, whether they are specific for dopaminergic stimulants such as cocaine and amphetamine and whether they are related to cognitive functions such as working memory, encoding and consolidation. In 47 occasional and 29 dependent cocaine users, 23 MDMA (commonly known as 'ecstasy') users and 47 stimulant-naive controls, colour vision discrimination was measured with the Lanthony Desaturated Panel D-15 Test and memory performance with the Auditory Verbal Learning Test. Both occasional and dependent cocaine users showed higher colour confusion indices than controls. Users of the serotonergic stimulant MDMA (26%), occasional (30%) and dependent cocaine users (34%) exhibited more frequent blue-yellow colour vision disorders compared to controls (9%). Inferior performance of MDMA users was caused by a subgroup with high amphetamine co-use (55%), while MDMA use alone was not associated with decreased blue-yellow discrimination (0%). Cognitive performance was worse in cocaine users with colour vision disorder compared to users and controls with intact colour vision and both colour vision impairment and cognitive deficits were related to cocaine use. Occasional cocaine and amphetamine use might induce blue-yellow colour vision impairment, whereas the serotonergic stimulant MDMA does not impair colour vision. The association between colour vision impairment and cognitive deficits in cocaine users may reflect that retinal and cerebral dopamine alterations are linked to a certain degree.
Ando, Susumu; Kobayashi, Satoru; Waki, Hatsue; Kon, Kazuo; Fukui, Fumiko; Tadenuma, Tomoko; Iwamoto, Machiko; Takeda, Yasuo; Izumiyama, Naotaka; Watanabe, Kazutada; Nakamura, Hiroaki
A rat dementia model with cognitive deficits was generated by synapse-specific lesions using botulinum neurotoxin (BoNTx) type B in the entorhinal cortex. To detect cognitive deficits, different tasks were needed depending upon the age of the model animals. Impaired learning and memory with lesions were observed in adult rats using the Hebb-Williams maze, AKON-1 maze and a continuous alternation task in T-maze. Cognitive deficits in lesioned aged rats were detected by a continuous alternation and delayed non-matching-to-sample tasks in T-maze. Adenovirus-mediated BDNF gene expression enhanced neuronal plasticity, as revealed by behavioral tests and LTP formation. Chronic administration of carnitine over time pre- and post-lesions seemed to partially ameliorate the cognitive deficits caused by the synaptic lesion. The carnitine-accelerated recovery from synaptic damage was observed by electron microscopy. These results demonstrate that the BoNTx-lesioned rat can be used as a model for dementia and that cognitive deficits can be alleviated in part by BDNF gene transfer or carnitine administration. Copyright 2002 Wiley-Liss, Inc.
Squarzoni, Paula; Tamashiro-Duran, Jaqueline H; Duran, Fabio L S; Leite, Claudia C; Wajngarten, Mauricio; Scazufca, Marcia; Menezes, Paulo R; Lotufo, Paulo A; Alves, Tania C T F; Busatto, Geraldo F
Using magnetic resonance imaging, we aimed to assess the presence of silent brain vascular lesions in a sample of apparently healthy elderly individuals who were recruited from an economically disadvantaged urban region (São Paulo, Brazil). We also wished to investigate whether the findings were associated with worse cognitive performance. A sample of 250 elderly subjects (66-75 years) without dementia or neuropsychiatric disorders were recruited from predefined census sectors of an economically disadvantaged area of Sao Paulo and received structural magnetic resonance imaging scans and cognitive testing. A high proportion of individuals had very low levels of education (4 years or less, n=185; 21 with no formal education). The prevalence of at least one silent vascular-related cortical or subcortical lesion was 22.8% (95% confidence interval, 17.7-28.5), and the basal ganglia was the most frequently affected site (63.14% of cases). The subgroup with brain infarcts presented significantly lower levels of education than the subgroup with no brain lesions as well as significantly worse current performance in cognitive test domains, including memory and attention (pcognitive deficits, and in the absence of magnetic resonance imaging data, this cognitive impairment may be considered simply related to ageing. Emphatic attention should be paid to potentially deleterious effects of vascular brain lesions in poorly educated elderly individuals from economically disadvantaged environments.
Lloyd, Anthony; Brett, David; Wesnes, Keith
Attention-deficit hyperactivity disorder (ADHD) is the most prevalent behavioral diagnosis in children, with an estimated 500 000 children affected in the United Kingdom alone. The need for an appropriate and effective intervention for children with ADHD is a growing concern for educators and childcare agencies. This randomized controlled clinical trial evaluated the impact of the HeartMath self-regulation skills and coherence training program (Institute of HeartMath, Boulder Creek, California) on a population of 38 children with ADHD in academic year groups 6, 7, and 8. Learning of the skills was supported with heart rhythm coherence monitoring and feedback technology designed to facilitate self-induced shifts in cardiac coherence. The cognitive drug research system was used to assess cognitive functioning as the primary outcome measure. Secondary outcome measures assessed teacher and student reposted changes in behavior. Participants demonstrated significant improvements in various aspects of cognitive functioning such as delayed word recall, immediate word recall, word recognition, and episodic secondary memory. Significant improvements in behavior were also found. The results suggest that the intervention offers a physiologically based program to improve cognitive functioning in children with ADHD and improve behaviors that is appropriate to implement in a school environment.
Sean M. Molnar
Full Text Available Heavy episodic drinking is prevalent among young adults and is a public issue of increasing importance. Its initiation and maintenance are associated with deficits in the capacity to inhibit automatic processing in favor of non-habitual responses. This study used functional magnetic resonance imaging (fMRI to examine behavioral and brain activity indices of cognitive control during the Stroop task as a function of binge drinking. Heavy episodic drinkers (HED reported consuming 5+/6+ drinks in two hours at least five times in the past six months and were compared to light drinkers (LED who reported two or fewer binge episodes but were matched on demographics, intelligence and family history of alcoholism. Greater conflict-induced activity in the ventrolateral prefrontal cortex (VLPFC and thalamus was observed in HED participants and it was positively correlated with alcohol intake and alcohol-related harmful consequences. HEDs maintained intact accuracy but at a cost of prolonged reaction times to high-conflict trials and increased ratings of task difficulty. Greater activation of the areas implicated in cognitive control is consistent with compensatory network expansion to meet higher cognitive demands. These results provide further insight into degradation of cognitive control in HEDs which may benefit development of detection and prevention strategies.
Full Text Available Abstract Introduction: Intracerebroventricular (ICV injection of streptozotocin (STZ causes cognitive impairment in rats. The beneficial effect of genistein (GEN was investigated on ICV STZ-induced learning, memory, and cognitive impairment in male rats. Methods: For this purpose, rats were injected with ICV STZ bilaterally, on days 1 and 3 (3 mg/kg. The STZ-injected rats received GEN (1 mg/kg/day, p.o. starting one day pre-surgery for two weeks. The learning and memory performance was assessed using passive avoidance paradigm, and for spatial cognition evaluation, radial eight-arm maze (RAM task was used. Results: It was found out that GEN-treated STZ-injected rats show higher correct choices and lower errors in RAM than vehicle-treated STZ-injected rats. In addition, GEN administration significantly attenuated learning and memory impairment in treated STZ-injected group in passive avoidance test.Discussion: These results demonstrate the effectiveness of GEN in preventing the cognitive deficits caused by ICV STZ in rats and its potential in the treatment of neurodegenerative diseases such as Alzheimer's disease (AD.
Full Text Available Abstract Introduction: Intracerebroventricular (ICV injection of streptozotocin (STZ causes cognitive impairment in rats. The beneficial effect of genistein (GEN was investigated on ICV STZ-induced learning, memory, and cognitive impairment in male rats. Methods: For this purpose, rats were injected with ICV STZ bilaterally, on days 1 and 3 (3 mg/kg. The STZ-injected rats received GEN (1 mg/kg/day, p.o. starting one day pre-surgery for two weeks. The learning and memory performance was assessed using passive avoidance paradigm, and for spatial cognition evaluation, radial eight-arm maze (RAM task was used. Results: It was found out that GEN-treated STZ-injected rats show higher correct choices and lower errors in RAM than vehicle-treated STZ-injected rats. In addition, GEN administration significantly attenuated learning and memory impairment in treated STZ-injected group in passive avoidance test.Discussion: These results demonstrate the effectiveness of GEN in preventing the cognitive deficits caused by ICV STZ in rats and its potential in the treatment of neurodegenerative diseases such as Alzheimer's disease (AD.
Karageorgiou, Elissaios; Lewis, Scott M.; Riley McCarten, J.; Leuthold, Arthur C.; Hemmy, Laura S.; McPherson, Susan E.; Rottunda, Susan J.; Rubins, David M.; Georgopoulos, Apostolos P.
In previous work (Georgopoulos et al 2007 J. Neural Eng. 4 349-55) we reported on the use of magnetoencephalographic (MEG) synchronous neural interactions (SNI) as a functional biomarker in Alzheimer's dementia (AD) diagnosis. Here we report on the application of canonical correlation analysis to investigate the relations between SNI and cognitive neuropsychological (NP) domains in AD patients. First, we performed individual correlations between each SNI and each NP, which provided an initial link between SNI and specific cognitive tests. Next, we performed factor analysis on each set, followed by a canonical correlation analysis between the derived SNI and NP factors. This last analysis optimally associated the entire MEG signal with cognitive function. The results revealed that SNI as a whole were mostly associated with memory and language, and, slightly less, executive function, processing speed and visuospatial abilities, thus differentiating functions subserved by the frontoparietal and the temporal cortices. These findings provide a direct interpretation of the information carried by the SNI and set the basis for identifying specific neural disease phenotypes according to cognitive deficits.
Schirmbeck, Frederike; Rausch, Franziska; Englisch, Susanne; Eifler, Sarah; Esslinger, Christine; Meyer-Lindenberg, Andreas; Zink, Mathias
Amongst schizophrenia patients, a large subgroup of up to 25% also suffers from comorbid obsessive-compulsive symptoms (OCSs). The association between comorbid OCSs in these patients and neuropsychological impairment remains unclear and somewhat contradictory. Longitudinal approaches investigating the stability of OCS-associated cognitive deficits are missing. Thirty-seven patients with schizophrenia and comorbid OCSs and 43 schizophrenia patients without OCS were assessed with a comprehensive cognitive test battery and compared at baseline and, again, 12 months later. Schizophrenia patients with comorbid OCSs showed significant pronounced deficits, with increasing effect sizes over the 12-month assessment period in specific cognitive areas such as visuospatial perception and visual memory (WAIS-R block design, Rey-Osterrieth Complex Figure Test), executive functioning (perseveration in the Wisconsin Card Sorting test), and cognitive flexibility (Trail Making test B). These cognitive domains are correlated with OCS severity and are known to be candidate cognitive domains in obsessive-compulsive disorder (OCD). OCSs in schizophrenia is associated with specific and longitudinally stable cognitive deficits, strongly arguing for at least partially overlapping neurobiological mechanisms with OCD. Prospective studies involving patients with at-risk mental states for psychosis are necessary to decipher the interaction of cognitive impairment and the clinical manifestations of schizophrenia and OCSs. This might facilitate the definition of patients at high risk for OCSs, an early detection of subclinical levels, therapeutic interventions, and clinical monitoring.
Jensen, Maria Høj; Glenthøj, Birte Yding; Nielsen, Mette Ødegaard
first-episode antipsychotic-naïve schizophrenia patients and 60 matched healthy controls have been examined at baseline. The study uses several instruments, including BACS (Brief Assessment of Cognition in Schizophrenia) and CANTAB (Cambridge Neuropsychological Test Automated Battery). Premorbid......Background and Aims: Cognitive deficits are considered a core feature of schizophrenia with prevalence estimates ranging from ca. 75-85 %. These deficits are present in the early phase of the illness; however in most first-episode schizophrenia studies the patients are receiving antipsychotic...... medication, which can affect the results on specific domains such as processing speed. As part of the PECANS project (Pan European Collaboration on Antipsychotic Naïve Schizophrenia) the aim of the present study is to establish the prevalence and profile of cognitive deficits in a cohort of first...
Chang, Linda; Lim, Ahnate; Lau, Eric; Alicata, Daniel
HIV-infected individuals (HIV+) has 2-3 times the rate of tobacco smoking than the general population, and whether smoking may lead to greater psychiatric symptoms or cognitive deficits remains unclear. We evaluated the independent and combined effects of being HIV+ and chronic tobacco-smoking on impulsivity, psychopathological symptoms and cognition. 104 participants [27 seronegative (SN)-non-Smokers, 26 SN-Smokers, 29 HIV+ non-Smokers, 22 HIV+ Smokers] were assessed for psychopathology symptoms (Symptom Checklist-90, SCL-90), depressive symptoms (Center for Epidemiologic Studies-Depression Scale, CES-D), impulsivity (Barratt Impulsiveness Scale, BIS), decision-making (The Iowa Gambling Task, IGT, and Wisconsin Card Sorting Test, WCST), and cognition (seven neurocognitive domains). Both HIV+ and Smoker groups had higher SCL-90 and CES-D scores, with highest scores in HIV+ Smokers. On BIS, both HIV+ and Smokers had higher Total Impulsiveness scores, with higher behavioral impulsivity in Smokers, highest in HIV+ Smokers. Furthermore, across the four groups, HIV+ Smokers lost most money and made fewest advantageous choices on the IGT, and had highest percent errors on WCST. Lastly, HIV+ had lower z-scores on all cognitive domains, with the lowest scores in HIV+ Smokers. These findings suggest that HIV-infection and chronic tobacco smoking may lead to additive deleterious effects on impulsivity, psychopathological (especially depressive) symptoms and cognitive dysfunction. Although greater impulsivity may be premorbid in HIV+ and Smokers, the lack of benefits of nicotine in chronic Smokers on attention and psychopathology, especially those with HIV-infection, may be due to the negative effects of chronic smoking on dopaminergic and cardio-neurovascular systems. Tobacco smoking may contribute to psychopathology and neurocognitive disorders in HIV+ individuals.
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.
Kennedy, David O; Scholey, Andrew B
Effects of a combination of caffeine and glucose were assessed in two double-blind, placebo-controlled, cross-over studies during extended performance of cognitively demanding tasks. In the first study, 30 participants received two drinks containing carbohydrate and caffeine (68 g/38 mg; 68 g/46 mg, respectively) and a placebo drink, in counter-balanced order, on separate days. In the second study 26 participants received a drink containing 60 g of carbohydrate and 33 mg of caffeine and a placebo drink. In both studies, participants completed a 10-min battery of tasks comprising 2-min versions of Serial 3s and Serial 7s subtraction tasks and a 5-min version of the Rapid Visual Information Processing task (RVIP), plus a rating of 'mental fatigue', once before the drink and six times in succession commencing 10 min after its consumption. In comparison to placebo, all three active drinks improved the accuracy of RVIP performance and both the drink with the higher level of caffeine in first study and the active drink in the second study resulted in lower ratings of mental fatigue. These results indicate that a combination of caffeine and glucose can ameliorate deficits in cognitive performance and subjective fatigue during extended periods of cognitive demand.
Zarafshan, Hadi; Khaleghi, Ali; Mohammadi, Mohammad Reza; Moeini, Mahdi; Malmir, Nastaran
The aim of this study was to investigate electroencephalogram (EEG) dynamics using complexity analysis in children with attention-deficit/hyperactivity disorder (ADHD) compared with healthy control children when performing a cognitive task. Thirty 7-12-year-old children meeting Diagnostic and Statistical Manual of Mental Disorders-Fifth Edition (DSM-5) criteria for ADHD and 30 healthy control children underwent an EEG evaluation during a cognitive task, and Lempel-Ziv complexity (LZC) values were computed. There were no significant differences between ADHD and control groups on age and gender. The mean LZC of the ADHD children was significantly larger than healthy children over the right anterior and right posterior regions during the cognitive performance. In the ADHD group, complexity of the right hemisphere was higher than that of the left hemisphere, but the complexity of the left hemisphere was higher than that of the right hemisphere in the normal group. Although fronto-striatal dysfunction is considered conclusive evidence for the pathophysiology of ADHD, our arithmetic mental task has provided evidence of structural and functional changes in the posterior regions and probably cerebellum in ADHD.
Burbridge, Mark; Raazi, Mateen
To describe the complex perioperative considerations and anesthetic management of a cognitively delayed blind adult male who underwent awake craniotomy to remove a left anterior temporal lobe epileptic focus. A 28-yr-old left-handed blind cognitively delayed man was scheduled for awake craniotomy to resect a left anterior temporal lobe epileptic focus due to intractable epilepsy despite multiple medications. His medical history was also significant for retinopathy of prematurity that rendered him legally blind in both eyes and an intracerebral hemorrhage shortly after birth that resulted in a chronic brain injury and developmental delay. His cognitive capacity was comparable with that of an eight year old. Since patient cooperation was the primary concern during the awake electrocorticography phase of surgery, careful assessment of the patient's ability to tolerate the procedure was undertaken. There was extensive planning between surgeons and anesthesiologists, and a patient-specific pharmacological strategy was devised to facilitate surgery. The operation proceeded without complication, the patient has remained seizure-free since the procedure, and his quality of life has improved dramatically. This case shows that careful patient assessment, effective interdisciplinary communication, and a carefully tailored anesthetic strategy can facilitate an awake craniotomy in a potentially uncooperative adult patient with diminished mental capacity and sensory deficits.
Bora, E; Pantelis, C
Impairment in social cognition is an established finding in autism spectrum disorders (ASD). Emerging evidence suggests that attention-deficit/hyperactivity disorder (ADHD) might be also associated with deficits in theory of mind (ToM) and emotion recognition. However, there are inconsistent findings, and it has been debatable whether such deficits persist beyond childhood and how similar social cognitive deficits are in ADHD v. ASD. We conducted a meta-analysis of social cognition, including emotion recognition and ToM, studies in ADHD compared with healthy controls and ASD. The current meta-analysis involved 44 studies comparing ADHD (n = 1999) with healthy controls (n = 1725) and 17 studies comparing ADHD (n = 772) with ASD (n = 710). Facial and vocal emotion recognition (d = 0.40-0.44) and ToM (d = 0.43) abilities were significantly impaired in ADHD. The most robust facial emotion recognition deficits were evident in anger and fear. Social cognitive deficits were either very subtle (emotion recognition) or non-significant (ToM) in adults with ADHD. Deficits in social cognition, especially ToM, were significantly more pronounced in ASD compared with ADHD. General cognitive impairment has contributed to social cognitive deficits in ADHD. Performance of individuals with ADHD on social cognition lies intermediate between ASD and healthy controls. However, developmental trajectories of social cognition probably differ between ADHD and ASD as social cognitive deficits in ADHD might be improving with age in most individuals. There is a need for studies investigating a potential subtype of ADHD with persistent social cognitive deficits and exploring longitudinal changes in social cognition during development.
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
Bell, Morris D; Vissicchio, Nicholas A; Weinstein, Andrea J
This study focused on the efficacy of cognitive training for verbal learning and memory deficits in a population of older veterans with alcohol use disorders. Veterans with alcohol use disorders, who were in outpatient treatment at VA facilities and in early-phase recovery (N = 31), were randomized to receive a three-month trial of daily cognitive training plus work therapy (n = 15) or work therapy alone (n = 16), along with treatment as usual. Participants completed assessments at baseline and at three- and six-month follow-ups; the Hopkins Verbal Learning Task (HVLT) was the primary outcome measure. Participants were primarily male (97%) and in their mid-50s (M = 55.16, SD = 5.16) and had been sober for 1.64 (SD = 2.81) months. Study retention was excellent (91% at three-month follow-up) and adherence to treatment in both conditions was very good. On average, participants in the cognitive training condition had more than 41 hours of cognitive training, and both conditions had more than 230 hours of productive activity. HVLT results at three-month follow-up revealed significant condition effects favoring cognitive training for verbal learning (HVLT Trial-3 T-score, p cognitive training condition with clinically significant verbal memory deficits (p therapy alone condition and a trend toward significance for verbal learning deficits, which was not sustained at six-month follow-up. This National Institute on Drug Abuse-funded pilot study demonstrates that cognitive training within the context of another activating intervention (work therapy) may have efficacy in remediating verbal learning and memory deficits in patients with alcohol use disorder. Findings indicate a large effect for cognitive training in this pilot study, which suggests that further research is warranted. This study is registered on ClinicalTrials.gov (NCT 01410110).
Ezeamama, AE; Bustinduy, AL; Nkwata, AK; Martinez, L; Pabalan, N; Boivin, MJ; King, CH
By means of meta-analysis of information from all relevant epidemiologic studies, we examined the hypothesis that Schistosoma infection in school-aged children (SAC) is associated with educational loss and cognitive deficits. This review was prospectively registered in the PROSPERO database (CRD42016040052). Medline, Biosis, and Web of Science were searched for studies published before August 2016 that evaluated associations between Schistosoma infection and cognitive or educational outcomes....
McIntosh, Roger C; Tartar, Jaime L; Widmayer, Susan; Rosselli, Monica
Deficits in emotional processing may be attributed to HIV disease or comorbid psychiatric disorders. Electrocortical markers of emotional attention, i.e., amplitude of the P2 and late positive potential (LPP), were compared between 26 HIV+ women and 25 healthy controls during an emotional regulation paradigm. HIV+ women showed early attention bias to negative stimuli indexed by greater P2 amplitude. In contrast, compared with the passive viewing of unpleasant images, HIV+ women demonstrated attenuation of the early and late LPP during positive reappraisal. This interaction remained significant after adjusting for individual differences in apathy, anxiety, and depression. Post hoc analyses implicated time since HIV diagnosis with LPP attenuation during positive reappraisal. Advancing HIV disease may disrupt neural generators associated with the cognitive reappraisal of emotions independent of psychiatric function.
Background: Many individuals with attention deficit hyperactivity disorder (ADHD) continue to experience impaired cognitive functions despite medical treatment. Inadequate medical compliance and uncertain long-term effects of treatment make it necessary to explore supplementary treatments for ADHD...... on the feasibility of the intervention. The first trial was exploratory and based on the results, the primary outcome measure in the second trial was sustained attention. Results: In the pilot trial with adolescents with ADHD, we found that it was feasible to use the intervention at home, but that the adolescents...... attention, while the active placebo had significant, beneficial effects on working memory, both with large effect sizes. In the second trial, we found no significant differences on our primary or secondary outcome measures indicating no effects on sustained attention, ADHD symptoms or executive functions...
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 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.
Devos, Hannes; Tant, Mark; Akinwuntan, Abiodun E
Little is known about the critical on-road driving skills that get affected after a stroke. The purpose of this study was to investigate the key on-road driving impairments and their associated cognitive deficits after a stroke. A second aim was to investigate if lateralization of stroke impacts results of the cognitive and on-road driving tests. In this cross-sectional study, 99 participants with a first-ever stroke who were actively driving prior to stroke underwent a cognitive battery and a standardized road test that evaluated 13 specific on-road driving skills. These on-road driving skills were mapped onto an existing, theoretical framework that categorized the on-road items into hierarchic clusters of operational, tactical, visuo-integrative, and mixed driving skills. The total score on the road test and the on-road decision, made by a certified fitness-to-drive expert, decided the main outcome. The critical on-road driving skills predicting the on-road decision were identified using logistic regression analysis. Linear regression analysis was employed to determine the cognitive impairments leading to poor total on-road scores. Analyses were repeated for right- and left-sided strokes. In all, 37 persons scored poorly on the road test. These participants performed worse in all hierarchic clusters of on-road driving. Performances on the operational cluster and the visuo-integrative cluster best predicted on-road decisions (R(2) = 0.60). 'Lane changing' and 'understanding, insight, and quality of traffic participation' were the critical skill deficits leading to poor performance on the road test (R(2) = 0.65). Divided attention was the main determinant of on-road scores in the total group (R(2) = 0.06). Participants with right-sided stroke performed worse on visual field, visual neglect, visual scanning, visuo-constructive skills, and divided attention compared with those with left-sided stroke. Divided attention was the main determinant of total on-road scores
Kuntsi, Jonna; Wood, Alexis C; Rijsdijk, Frühling; Johnson, Katherine A; Andreou, Penelope; Albrecht, Björn; Arias-Vasquez, Alejandro; Buitelaar, Jan K; McLoughlin, Gráinne; Rommelse, Nanda N J; Sergeant, Joseph A; Sonuga-Barke, Edmund J; Uebel, Henrik; van der Meere, Jaap J; Banaschewski, Tobias; Gill, Michael; Manor, Iris; Miranda, Ana; Mulas, Fernando; Oades, Robert D; Roeyers, Herbert; Rothenberger, Aribert; Steinhausen, Hans-Christoph; Faraone, Stephen V; Asherson, Philip
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 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. To determine, by using a multivariate familial factor analysis approach, whether 1 or more familial factors underlie the slow and variable reaction times, impaired response inhibition, and choice impulsivity associated with ADHD. An ADHD and control sibling-pair design. Belgium, Germany, Ireland, Israel, Spain, Switzerland, and the United Kingdom. A total of 1265 participants, aged 6 to 18 years: 464 probands with ADHD and 456 of their siblings (524 with combined-subtype ADHD), and 345 control participants. Performance on a 4-choice reaction time task, a go/no-go inhibition task, and a choice-delay task. The final model consisted of 2 familial factors. The larger factor, reflecting 85% of the familial variance of ADHD, captured 98% to 100% of the familial influences on mean reaction time and reaction time variability. The second, smaller factor, reflecting 13% of the familial variance of ADHD, captured 62% to 82% of the familial influences on commission and omission errors on the go/no-go task. Choice impulsivity was excluded in the final model because of poor fit. The findings suggest the existence of 2 familial pathways to cognitive impairments in ADHD and indicate promising cognitive targets for future molecular genetic investigations. The familial distinction between the 2 cognitive impairments is consistent with recent theoretical models--a developmental model and an arousal-attention model--of 2 separable underlying processes in ADHD. Future research that tests the familial model within a developmental framework may inform
He, Zhi; Liao, Yun; Zheng, Min; Zeng, Fan-Dian; Guo, Lian-Jun
Piracetam is the derivate of gamma-aminobutyric acid, which improves the cognition,memory,consciousness, and is widely applied in the clinical treatment of brain dysfunction. In the present experiments, we study the effects of piracetam on chronic cerebral hypoperfused rats and observe its influence on amino acids, synaptic plasticity in the Perforant path-CA3 pathway and apoptosis in vivo. Cerebral hypoperfusion for 30 days by occlusion of bilateral common carotid arteries induced marked amnesic effects along with neuron damage, including: (1) spatial learning and memory deficits shown by longer escape latency and shorter time spent in the target quadrant; (2) significant neuronal loss and nuclei condensation in the cortex and hippocampus especially in CA1 region; (3) lower induction rate of long term potentiation, overexpression of BAX and P53 protein, and lower content of excitatory and inhibitory amino acids in hippocampus. Oral administration of piracetam (600 mg/kg, once per day for 30 days) markedly improved the memory impairment, increased the amino acid content in hippocampus, and attenuated neuronal damage. The ability of piracetam to attenuate memory deficits and neuronal damage after hypoperfusion may be beneficial in cerebrovascular type dementia.
Malloy-Diniz, L; Fuentes, D; Leite, W Borges; Correa, H; Bechara, A
Attention-deficit/hyperactivity disorder (ADHD) is characterized by inattention and/or hyperactivity/impulsivity. Impulsivity persists in adults with ADHD and might be the basis of much of the impairment observed in the daily lives of such individuals. The objective of this study was to address the presence, and more importantly, the three dimensions of impulsivity: attentional, non-planning and motor, in how they may relate to neuropsychological mechanisms of impulse control. We studied a sample of 50 adults with ADHD and 51 healthy comparison controls using the Barratt Impulsivity Scale Version 11 (BIS), and neuropsychological tasks, namely the Continuous Performance Task (CPT-II) and the Iowa Gambling Task (IGT). The ADHD group showed more signs of impulsivity on the three dimensions of BIS, committed more errors of omission and commission on the CPT-II, and made more disadvantageous choices on the IGT. These results support the existence of deficits related to three components of impulsivity: motor, cognitive, and attentional among adults with ADHD. Most importantly, this study also highlights the complementary nature of self-report questionnaires and neuropsychological tasks in the assessment of impulsivity in ADHD adults.
Marlijn H. de Beer
Full Text Available Background/Aim: To explore the theory of ‘growing into deficits', a concept known from developmental neurology, in a series of cases with chronic hydrocephalus (CH. Methods: Patients were selected from the Amsterdam Dementia Cohort and underwent extensive dementia screening. Results: Twelve patients with CH were selected, in whom Alzheimer's disease was considered unlikely, based on biomarker information and follow-up. Mean Mini-Mental State Examination score was 24 (range 7-30. Most patients were functioning on a level of mild dementia [Clinical Dementia Rating score of 0.5 in 8/11 (66.7% patients]. On neuropsychological examination, memory and executive functions, as well as processing speed were most frequently impaired. Conclusion: In our opinion, the theory of ‘growing into deficits' shows a parallel with the clinical course of CH and normal aging when Alzheimer's disease was considered very unlikely, because most of these patients were functioning well for a very large part of their lives. The altered cerebrospinal fluid dynamics might make the brain more vulnerable to aging-related changes, leading to a faster cognitive decline in CH patients compared to healthy subjects, especially in case of concomitant brain damage such as traumatic brain injury or meningitis.
Full Text Available ENGRAILED 2 (En2, a homeobox transcription factor, functions as a patterning gene in the early development and connectivity of rodent hindbrain and cerebellum, and regulates neurogenesis and development of monoaminergic pathways. To further understand the neurobiological functions of En2, we conducted neuroanatomical expression profiling of En2 wildtype mice. RTQPCR assays demonstrated that En2 is expressed in adult brain structures including the somatosensory cortex, hippocampus, striatum, thalamus, hypothalamus and brainstem. Human genetic studies indicate that EN2 is associated with autism. To determine the consequences of En2 mutations on mouse behaviors, including outcomes potentially relevant to autism, we conducted comprehensive phenotyping of social, communication, repetitive, and cognitive behaviors. En2 null mutants exhibited robust deficits in reciprocal social interactions as juveniles and adults, and absence of sociability in adults, replicated in two independent cohorts. Fear conditioning and water maze learning were impaired in En2 null mutants. High immobility in the forced swim test, reduced prepulse inhibition, mild motor coordination impairments and reduced grip strength were detected in En2 null mutants. No genotype differences were found on measures of ultrasonic vocalizations in social contexts, and no stereotyped or repetitive behaviors were observed. Developmental milestones, general health, olfactory abilities, exploratory locomotor activity, anxiety-like behaviors and pain responses did not differ across genotypes, indicating that the behavioral abnormalities detected in En2 null mutants were not attributable to physical or procedural confounds. Our findings provide new insight into the role of En2 in complex behaviors and suggest that disturbances in En2 signaling may contribute to neuropsychiatric disorders marked by social and cognitive deficits, including autism spectrum disorders.
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…
Åsberg Johnels, Jakob; Kopp, Svenny; Gillberg, Christopher
Writing difficulties are common among children with attention-deficit/hyperactivity disorder (ADHD), but the nature of these difficulties has not been well studied. Here we relate behavioral, psycholinguistic, cognitive (memory/executive), and graphomotor measures to spelling skills in school-age girls with ADHD (n = 30) and an age-matched group…
Dijk, F.E. van; Schellekens, A.F.A.; Broek, P.J.A. van den; Kan, C.C.; Verkes, R.J.; Buitelaar, J.K.
This study examined whether cognitive measures of response inhibition derived from the AX-CPT are able to differentiate between adult attention deficit/hyperactivity disorder (ADHD), borderline personality disorder (BPD), and healthy controls (HC). Current DSM-IV-TR symptoms of ADHD and BPD were
Shillingford, Margaret Ann; Lambie, Glenn W.; Walter, Sara Meghan
Attention deficit hyperactive disorder (ADHD) is a prevalent diagnostic disorder for many students, which correlates with negative academic, social, and personal consequences. This article presents an integrative, cognitive-behavioral, systemic approach that offers behaviorally based interventions for professional school counselors to support…
Schoenberg, P.L.; Hepark, S.; Kan, C.C.; Barendregt, H.P.; Buitelaar, J.K.; Speckens, A.E.M.
OBJECTIVE: To examine whether mindfulness-based cognitive therapy (MBCT) would enhance attenuated amplitudes of event-related potentials (ERPs) indexing performance monitoring biomarkers of attention-deficit/hyperactivity disorder (ADHD). METHODS: Fifty adult ADHD patients took part in a randomised
Cherkil, Sandhya; Panikar, Dilip; Soman, Deepak Kuttikkattu
Tumors of the brain, whether intra- or extra-axial, results in cognitive deficits. The aim of the present study was to profile cognitive deficits using Addenbrooke's Cognitive Examination-Malayalam (ACE-M) as a screen and to determine the sensitivity and specificity of the same. Seventy-four drug naïve patients diagnosed to have brain tumors were assessed for cognitive functioning using ACE-M before surgery. Patients with high-grade intra-axial tumors showed a significant association on the cognitive domains of registration (0.04), recall (0.01), and visuospatial functioning (0.02). Gender showed an association between registration (0.02) and verbal fluency (0.02) with females performing better while education was significantly associated with retrograde or remote memory (0.00) with college-educated sample performing better. Significance was assumed at P cognitive decline on the cognitive domains of attention (0.02), recall (0.05), naming (0.02), and language functions (0.01). College educated group performed better on registration (0.01), recall (0.09), naming (0.00), and visuospatial functioning (0.00). The area under the receiver operating characteristic curve was estimated as 0.75, which indicates fairly good discriminative ability with a cut off of 71/100; sensitivity at 77.3 and specificity fixed at 67. ACE-M is capable of bringing out cognitive deficits along with a number of cognitive domains in patients with intra- and extra-axial tumors in the capacity of a screen, with fairly good levels of sensitivity and specificity.
Full Text Available Attention-Deficit Hyperactivity Disorder (ADHD is a neuropsychiatric disorder characterized by inattention, distractibility, and impulsivity. Scholastic competence, social acceptance, and behavioral conduct were problem areas for children with ADHD. These children have difficulties in regulating their emotions and maintaining good relations. Lack of these skills hinders the development of healthy peer relationships and positive interaction with adults. It is important for children with ADHD to receive interventions as early as possible so that their social and emotional development can be achieved. Some social skills training programs for school-ages children with ADHD have shown positive results. The research findings in the literature demonstrate that interpersonal problem-solving skills are teachable and learnable through properly structured education programmes. Social problem solving training for children with ADHD has positive effects on the academic, behavioral and cognitive impairment. The Interpersonal Cognitive Problem-Solving (ICPS Program can have a significant effect on the behaviors of children with ADHD and can generalize to settings outside of the one in which the child was initially trained. The positive effectiveness of ICPS also known as I Can Problem Solve in developing problem-solving skills and reducing problem behaviors of children with ADHD is known. [TAF Prev Med Bull 2010; 9(4.000: 391-398
Shukitt-Hale, Barbara; Carey, Amanda; Simon, Laura; Mark, David A; Joseph, James A
Animals and humans show increased motor and cognitive declines with aging that are thought to be due to increased susceptibility to the long-term effects of oxidative stress and inflammation. Previous findings have suggested that reversals in these age-related declines might be accomplished by increasing the dietary intake of polyphenolics found in fruits and vegetables, especially those identified as being high in antioxidant and anti-inflammatory activities. We investigated the beneficial effects of two concentrations of Concord grape juice (10% and 50%) compared with a calorically matched placebo for their effectiveness in reversing age-related deficits in behavioral and neuronal functions in aged Fischer 344 rats. Rats that drank the 10% grape juice from age 19 to 21 mo had improvements in oxotremorine enhancement of K+-evoked release of dopamine from striatal slices and in cognitive performance on the Morris water maze, and the 50% grape juice produced improvements in motor function. These findings suggest that, in addition to their known beneficial effects on cancer and heart disease, polyphenolics in foods may be beneficial in reversing the course of neuronal and behavioral aging, possibly through a multiplicity of direct and indirect effects that can affect a variety of neuronal parameters.
Healey, Dione M; Marks, David J; Halperin, Jeffrey M
Cognition and emotion, traditionally thought of as largely distinct, have recently begun to be conceptualized as dynamically linked processes that interact to influence functioning. This study investigated the moderating effects of cognitive functioning on the relationship between negative emotionality and attention deficit/hyperactivity disorder (ADHD) symptom severity. A total of 216 (140 hyperactive/inattentive; 76 typically developing) preschoolers aged 3-4 years were administered a neuropsychological test battery (i.e., NEPSY). To avoid method bias, child negative emotionality was rated by teachers (Temperament Assessment Battery for Children-Revised), and parents rated symptom severity on the ADHD Rating Scale (ADHD-RS-IV). Hierarchical Linear Regression analyses revealed that both negative emotionality and Perceptual-Motor & Executive Functions accounted for significant unique variance in ADHD symptom severity. Significant interactions indicated that when negative emotionality is low, but not high, neuropsychological functioning accounts for significant variability in ADHD symptoms, with lower functioning predicting more symptoms. Emotional and neuropsychological functioning, both individually and in combination, play a significant role in the expression of ADHD symptom severity.
Zheng, Wei; Xiang, Ying-Qiang; Li, Xian-Bin; Ungvari, Gabor S; Chiu, Helen F K; Sun, Feng; D'Arcy, Carl; Meng, Xiangfei; Xiang, Yu-Tao
The aim of this study was to examine the efficacy of huperzine A (HupA), an isolate of Huperzine serrata, in the treatment of cognitive deficits in schizophrenia spectrum disorders. PubMed, PsycINFO, Embase, Cochrane Library, Cochrane Controlled Trials Register, WanFang, Chinese Biomedical, and China Journal Net databases were searched from inception to 15 July 2015 for randomized controlled trials (RCTs) in English or Chinese of HupA augmentation of antipsychotic drug therapy versus placebo or ongoing antipsychotic treatment. Twelve RCTs (n = 1117) lasting 11.7 ± 6.0 weeks met inclusion criteria. All had been conducted in China. HupA outperformed comparators on the following outcome measures: the Wechsler Memory Scale-Revised including memory quotient (weighted mean difference (WMD: 10.59; 95% confidence interval (CI): 5.65, 15.53; p HupA is an effective choice for improving cognitive function for patients with schizophrenia spectrum disorders. More well-designed RCTs are needed to further confirm HupA's efficacy. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.
Thomaidis, L; Choleva, A; Janikian, M; Bertou, G; Tsitsika, A; Giannakopoulos, G; Anagnostopoulos, D C
Attention deficit/hyperactivity disorder (ADHD) constitutes a neurobehavioral disorder which may potentially adversely affect children's wellbeing and academic achievement. The onset of symptoms is present prior to 12 years of age, and often the symptoms are evident in the preschool years. In fact, it has been suggested that screening for ADHD symptoms may be initiated as early as four years of age. Preschool children with ADHD have been shown to present with poor pre-academic skills and might be at increased risk for numerous school-related problems, including functional impairment during elementary school years and persistent poor academic performance thereafter. Although preschool years are characterized by rapid cognitive growth, preschoolers with ADHD may present with poorer cognitive and neuropsychological functioning. Due to the early onset of ADHD symptoms, exploring the cognitive correlates of this condition among preschool children is thought to be of notable importance. The aim of the present study was to evaluate any association between ADHD symptoms and cognitive skills among preschool children. A cross-sectional study was conducted among a nationwide random sample of 4,480 preschool children. ADHD symptoms were assessed though interviews with parents and teachers based on DSM-IV-TR criteria. Cognitive skills were assessed through a standardized school readiness test (A' TEST). Among participants, the occurrence of ADHD symptoms was 4.6% (boys/girls: 3.4/1). The presence of ADHD symptoms among children was inversely associated with non-verbal and verbal cognitive skills; specifically, with abstract thinking (aOR 1.97, 95% CI 1.30-3.00), language (2.36, 1.55-3.59), critical reasoning (2.58, 1.84-3.62), visual perception (2.42, 1.38- 4.24), and visual motor skills (2.61, 1.91-3.55). Children with ADHD symptoms were five times as likely to have compromised organizational skills (4.92, 3.04-7.97). Abstract thinking was the least affected domain
Lidzba, Karen; Granstroem, Sofia; Leark, Robert A; Kraegeloh-Mann, Inge; Mautner, Victor-Felix
Attention deficit with or without hyperactivity (AD[H]D) is a common comorbidity of neurofibromatosis type 1 (NF 1). We tested the hypothesis that permanent medication with methylphenidate can improve cognitive functioning in children with NF 1 and comorbid AD(H)D. We retrospectively analyzed data of a clinical sample of patients with NF 1 with or without AD(H)D, who underwent standardized neuropsychological diagnostics twice (age range: T1, 6-14 years; T2, 7-16 years; mean interval, 49.09 months). A total of 16 children without AD(H)D (nine females) were compared with 14 unmedicated children with AD(H)D (eight females) and to 13 medicated children with AD(H)D (two females). Effects of medication and attention on cognitive outcome (IQ) were tested by repeated measures analysis of covariance (rmANCOVA). Medicated children with NF 1 improved significantly in full-scale IQ from T1 to T2 (IQ[T1] = 80.38, IQ[T2] = 98.38, confidence interval [diff]: -25.59 to -10.40, p attention measures as covariates, the effect remained marginally significant. Children and adolescents with NF 1 and comorbid AD(H)D may profit from MPH medication regarding general cognition. This effect could be specific for the group of patients with NF 1, and cannot be explained solely by improvements in attention. Controlled, prospective studies are warranted to corroborate our findings. Georg Thieme Verlag KG Stuttgart · New York.
Full Text Available Prenatal ethanol exposure is associated with deficits in executive function such as working memory, reversal learning and attentional set shifting in humans and animals. These behaviors are dependent on normal structure and function in cholinergic brain regions. Supplementation with choline can improve many behaviors in rodent models of fetal alcohol spectrum disorders and also improves working memory function in normal rats. We tested the hypothesis that supplementation with choline in the postnatal period will improve working memory during adolescence in normal and ethanol-exposed animals, and that working memory engagement during adolescence will transfer to other cognitive domains and have lasting effects on executive function in adulthood. Male and female offspring of rats fed an ethanol-containing liquid diet (ET; 3% v/v or control dams given a non-ethanol liquid diet (CT were injected with choline (Cho; 100 mg/kg or saline (Sal once per day from postnatal day (P 16–P30. Animals were trained/tested on a working memory test in adolescence and then underwent attentional set shifting and reversal learning in young adulthood. In adolescence, ET rats required more training to reach criterion than CT-Sal. Choline improved working memory performance for both CT and ET animals. In young adulthood, ET animals also performed poorly on the set shifting and reversal tasks. Deficits were more robust in ET male rats than female ET rats, but Cho improved performance in both sexes. ET male rats given a combination of Cho and working memory training in adolescence required significantly fewer trials to achieve criterion than any other ET group, suggesting that early interventions can cause a persistent improvement.
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. © 2014 John Wiley & Sons Ltd.
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.
Sudo, Felipe Kenji; Amado, Patricia; Alves, Gilberto Sousa; Laks, Jerson; Engelhardt, Eliasz
Subcortical Vascular Cognitive Impairment (SVCI) is a clinical continuum of vascular-related cognitive impairment, including Vascular Mild Cognitive Impairment (VaMCI) and Vascular Dementia. Deficits in Executive Function (EF) are hallmarks of the disorder, but the best methods to assess this function have yet to be determined. The insidious and almost predictable course of SVCI and the multidimensional concept of EF suggest that a temporal dissociation of impairments in EF domains exists early in the disorder. This study aims to review and analyze data from the literature about performance of VaMCI patients on the most used EF tests through a meta-analytic approach. Medline, Web of Knowledge and PsycINFO were searched, using the terms: "vascular mild cognitive impairment" OR "vascular cognitive impairment no dementia" OR "vascular mild neurocognitive disorder" AND "dysexecutive" OR "executive function". Meta-analyses were conducted for each of the selected tests, using random-effect models. Systematic review showed major discrepancies among the results of the studies included. Meta-analyses evidenced poorer performance on the Trail-Making Test part B and the Stroop color test by VaMCI patients compared to controls. A continuum of EF impairments has been proposed in SVCI. Early deficits appear to occur in cognitive flexibility and inhibitory control.
Bertoux, Maxime; de Souza, Leonardo Cruz; O'Callaghan, Claire; Greve, Andrea; Sarazin, Marie; Dubois, Bruno; Hornberger, Michael
Relative sparing of episodic memory is a diagnostic criterion of behavioral variant frontotemporal dementia (bvFTD). However, increasing evidence suggests that bvFTD patients can show episodic memory deficits at a similar level as Alzheimer's disease (AD). Social cognition tasks have been proposed to distinguish bvFTD, but no study to date has explored the utility of such tasks for the diagnosis of amnestic bvFTD. Here, we contrasted social cognition performance of amnestic and non-amnestic bvFTD from AD, with a subgroup having confirmed in vivo pathology markers. Ninety-six participants (38 bvFTD and 28 AD patients as well as 30 controls) performed the short Social-cognition and Emotional Assessment (mini-SEA). BvFTD patients were divided into amnestic versus non-amnestic presentation using the validated Free and Cued Selective Reminding Test (FCSRT) assessing episodic memory. As expected, the accuracy of the FCSRT to distinguish the overall bvFTD group from AD was low (69.7% ) with ∼50% of bvFTD patients being amnestic. By contrast, the diagnostic accuracy of the mini-SEA was high (87.9% ). When bvFTD patients were split on the level of amnesia, mini-SEA diagnostic accuracy remained high (85.1% ) for amnestic bvFTD versus AD and increased to very high (93.9% ) for non-amnestic bvFTD versus AD. Social cognition deficits can distinguish bvFTD and AD regardless of amnesia to a high degree and provide a simple way to distinguish both diseases at presentation. These findings have clear implications for the diagnostic criteria of bvFTD. They suggest that the emphasis should be on social cognition deficits with episodic memory deficits not being a helpful diagnostic criterion in bvFTD.
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. © 2015 Wiley Periodicals, Inc.
Yerys, Benjamin E; Wallace, Gregory L; Sokoloff, Jennifer L; Shook, Devon A; James, Joette D; Kenworthy, Lauren
Recent estimates suggest that 31% of children with autism spectrum disorders (ASD) meet diagnostic criteria for attention deficit/hyperactivity disorder (ADHD), and another 24% 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 problems unreported in ASD or ADHD; having no clear impact; or producing some combination of these scenarios. Children with ASD and co-morbid ADHD symptoms (ASD+ADHD; n = 21), children with ASD without ADHD (ASD; n = 28), and a typically developing control group (n = 21) were included in the study; all groups were matched on age, gender-ratio, IQ, and socioeconomic status. Data were collected on verbal and spatial working memory, response inhibition, global executive control (EC), autistic traits, adaptive functioning, and maladaptive behavior problems. In this sample, the presence of ADHD symptoms in ASD exacerbated impairments in EC and adaptive behavior and resulted in higher autistic trait, and externalizing behavior ratings. ADHD symptoms were also associated with greater impairments on a lab measure of verbal working memory. These findings suggest that children with ASD+ADHD symptoms present with exacerbated impairments in some but not all domains of functioning relative to children with ASD, most notably in adaptive behavior and working memory. Therefore, ADHD may moderate the expression of components of the ASD cognitive and behavioral phenotype, but ASD+ADHD may not represent an etiologically distinct phenotype from ASD alone.
Gupta, Rashmi; Kar, Bhoomika R; Srinivasan, Narayanan
The classification systems developed so far to detect attention deficit/hyperactivity disorder (ADHD) do not have high sensitivity and specificity. We have developed a classification system based on several neuropsychological tests that measure cognitive-motivational functions that are specifically impaired in ADHD children. A total of 240 (120 ADHD children and 120 healthy controls) children in the age range of 6-9 years and 32 Oppositional Defiant Disorder (ODD) children (aged 9 years) participated in the study. Stop-Signal, Task-Switching, Attentional Network, and Choice Delay tests were administered to all the participants. Receiver operating characteristic (ROC) analysis indicated that percentage choice of long-delay reward best classified the ADHD children from healthy controls. Single parameters were not helpful in making a differential classification of ADHD with ODD. Multinominal logistic regression (MLR) was performed with multiple parameters (data fusion) that produced improved overall classification accuracy. A combination of stop-signal reaction time, posterror-slowing, mean delay, switch cost, and percentage choice of long-delay reward produced an overall classification accuracy of 97.8%; with internal validation, the overall accuracy was 92.2%. Combining parameters from different tests of control functions not only enabled us to accurately classify ADHD children from healthy controls but also in making a differential classification with ODD. These results have implications for the theories of ADHD.
Obeso, Ignacio; Wilkinson, Leonora; Casabona, Enrique; Bringas, Maria Luisa; Álvarez, Mario; Álvarez, Lázaro; Pavón, Nancy; Rodríguez-Oroz, Maria-Cruz; Macías, Raúl; Obeso, Jose A; Jahanshahi, Marjan
Recent imaging studies in healthy controls with a conditional stop signal reaction time (RT) task have implicated the subthalamic nucleus (STN) in response inhibition and the pre-supplementary motor area (pre-SMA) in conflict resolution. Parkinson's disease (PD) is characterized by striatal dopamine deficiency and overactivity of the STN and underactivation of the pre-SMA during movement. We used the conditional stop signal RT task to investigate whether PD produced similar or dissociable effects on response initiation, response inhibition and response initiation under conflict. In addition, we also examined inhibition of prepotent responses on three cognitive tasks: the Stroop, random number generation and Hayling sentence completion. PD patients were impaired on the conditional stop signal reaction time task, with response initiation both in situations with or without conflict and response inhibition all being significantly delayed, and had significantly greater difficulty in suppressing prepotent or habitual responses on the Stroop, Hayling and random number generation tasks relative to controls. These results demonstrate the existence of a generalized inhibitory deficit in PD, which suggest that PD is a disorder of inhibition as well as activation and that in situations of conflict, executive control over responses is compromised.
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. Copyright © 2016, American Association for the Advancement of Science.
Janssen, Lotte; Kan, Cornelis C; Carpentier, Pieter J; Sizoo, Bram; Hepark, Sevket; Grutters, Janneke; Donders, Rogier; Buitelaar, Jan K; Speckens, Anne E M
Adults with attention deficit hyperactivity disorder (ADHD) often present with a lifelong pattern of core symptoms that is associated with impairments of functioning in daily life. This has a substantial personal and economic impact. In clinical practice there is a high need for additional or alternative interventions for existing treatments, usually consisting of pharmacotherapy and/or psycho-education. Although previous studies show preliminary evidence for the effectiveness of mindfulness-based interventions in reducing ADHD symptoms and improving executive functioning, these studies have methodological limitations. This study will take account of these limitations and will examine the effectiveness of Mindfulness Based Cognitive Therapy (MBCT) in further detail. A multi-centre, parallel-group, randomised controlled trial will be conducted in N = 120 adults with ADHD. Patients will be randomised to MBCT in addition to treatment as usual (TAU) or TAU alone. Assessments will take place at baseline and at three, six and nine months after baseline. Primary outcome measure will be severity of ADHD symptoms rated by a blinded clinician. Secondary outcome measures will be self-reported ADHD symptoms, executive functioning, mindfulness skills, self-compassion, positive mental health and general functioning. In addition, a cost-effectiveness analysis will be conducted. This trial will offer valuable information about the clinical and cost-effectiveness of MBCT in addition to TAU compared to TAU alone in adults swith ADHD. ClinicalTrials.gov NCT02463396. Registered 8 June 2015.
Berlingeri, Manuela; Ravasio, Alessandra; Cranna, Silvia; Basilico, Stefania; Sberna, Maurizio; Bottini, Gabriella; Paulesu, Eraldo
Three cognitive components may play a crucial role in both memory awareness and in anosognosia for memory deficit (AMD): (1) a personal data base (PDB), i.e., a memory store that contains "semantic" representations about the self, (2) monitoring processes (MPs) and (3) an explicit evaluation system (EES), or comparator, that assesses and binds the representations stored in the PDB with information obtained from the environment. We compared both the behavior and the functional connectivity (as assessed by resting-state fMRI) of AMD patients with aware patients and healthy controls. We found that AMD is associated with an impoverished PDB, while MPs are necessary to successfully update the PDB. AMD was associated with reduced functional connectivity within both the default-mode network and in a network that includes the left lateral temporal cortex, the hippocampus and the insula. The reduced connectivity between the hippocampus and the insular cortex was correlated with AMD severity. Copyright © 2015 Elsevier Inc. All rights reserved.
Monyak, R E; Emerson, D; Schoenfeld, B P; Zheng, X; Chambers, D B; Rosenfelt, C; Langer, S; Hinchey, P; Choi, C H; McDonald, T V; Bolduc, F V; Sehgal, A; McBride, S M J; Jongens, T A
Fragile X syndrome (FXS) is an undertreated neurodevelopmental disorder characterized by low intelligence quotent and a wide range of other symptoms including disordered sleep and autism. Although FXS is the most prevalent inherited cause of intellectual disability, its mechanistic underpinnings are not well understood. Using Drosophila as a model of FXS, we showed that select expression of dfmr1 in the insulin-producing cells (IPCs) of the brain was sufficient to restore normal circadian behavior and to rescue the memory deficits in the fragile X mutant fly. Examination of the insulin signaling (IS) pathway revealed elevated levels of Drosophila insulin-like peptide 2 (Dilp2) in the IPCs and elevated IS in the dfmr1 mutant brain. Consistent with a causal role for elevated IS in dfmr1 mutant phenotypes, the expression of dfmr1 specifically in the IPCs reduced IS, and genetic reduction of the insulin pathway also led to amelioration of circadian and memory defects. Furthermore, we showed that treatment with the FDA-approved drug metformin also rescued memory. Finally, we showed that reduction of IS is required at different time points to rescue circadian behavior and memory. Our results indicate that insulin misregulation underlies the circadian and cognitive phenotypes displayed by the Drosophila fragile X model, and thus reveal a metabolic pathway that can be targeted by new and already approved drugs to treat fragile X patients.
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.
Ezeamama, Amara E; Bustinduy, Amaya L; Nkwata, Allan K; Martinez, Leonardo; Pabalan, Noel; Boivin, Michael J; King, Charles H
By means of meta-analysis of information from all relevant epidemiologic studies, we examined the hypothesis that Schistosoma infection in school-aged children (SAC) is associated with educational loss and cognitive deficits. This review was prospectively registered in the PROSPERO database (CRD42016040052). Medline, Biosis, and Web of Science were searched for studies published before August 2016 that evaluated associations between Schistosoma infection and cognitive or educational outcomes. Cognitive function was defined in four domains-learning, memory, reaction time, and innate intelligence. Educational outcome measures were defined as attendance and scholastic achievement. Risk of bias (ROB) was evaluated using the Newcastle-Ottawa quality assessment scale. Standardized mean differences (SMD) and 95% confidence intervals (CI) were calculated to compare cognitive and educational measures for Schistosoma infected /not dewormed vs. uninfected/dewormed children. Sensitivity analyses by study design, ROB, and sequential exclusion of individual studies were implemented. Thirty studies from 14 countries, including 38,992 SAC between 5-19 years old, were identified. Compared to uninfected children and children dewormed with praziquantel, the presence of Schistosoma infection and/or non-dewormed status was associated with deficits in school attendance (SMD = -0.36, 95%CI: -0.60, -0.12), scholastic achievement (SMD = -0.58, 95%CI: -0.96, -0.20), learning (SMD = -0.39, 95%CI: -0.70, -0.09) and memory (SMD = -0.28, 95%CI: -0.52, -0.04) tests. By contrast, Schistosoma-infected/non-dewormed and uninfected/dewormed children were similar with respect to performance in tests of reaction time (SMD = -0.06, 95%CI: -0.42, 0.30) and intelligence (SMD = -0.25, 95%CI: -0.57, 0.06). Schistosoma infection-associated deficits in educational measures were robust among observational studies, but not among interventional studies. The significance of infection-associated deficits in
Amara E Ezeamama
Full Text Available By means of meta-analysis of information from all relevant epidemiologic studies, we examined the hypothesis that Schistosoma infection in school-aged children (SAC is associated with educational loss and cognitive deficits.This review was prospectively registered in the PROSPERO database (CRD42016040052. Medline, Biosis, and Web of Science were searched for studies published before August 2016 that evaluated associations between Schistosoma infection and cognitive or educational outcomes. Cognitive function was defined in four domains-learning, memory, reaction time, and innate intelligence. Educational outcome measures were defined as attendance and scholastic achievement. Risk of bias (ROB was evaluated using the Newcastle-Ottawa quality assessment scale. Standardized mean differences (SMD and 95% confidence intervals (CI were calculated to compare cognitive and educational measures for Schistosoma infected /not dewormed vs. uninfected/dewormed children. Sensitivity analyses by study design, ROB, and sequential exclusion of individual studies were implemented. Thirty studies from 14 countries, including 38,992 SAC between 5-19 years old, were identified. Compared to uninfected children and children dewormed with praziquantel, the presence of Schistosoma infection and/or non-dewormed status was associated with deficits in school attendance (SMD = -0.36, 95%CI: -0.60, -0.12, scholastic achievement (SMD = -0.58, 95%CI: -0.96, -0.20, learning (SMD = -0.39, 95%CI: -0.70, -0.09 and memory (SMD = -0.28, 95%CI: -0.52, -0.04 tests. By contrast, Schistosoma-infected/non-dewormed and uninfected/dewormed children were similar with respect to performance in tests of reaction time (SMD = -0.06, 95%CI: -0.42, 0.30 and intelligence (SMD = -0.25, 95%CI: -0.57, 0.06. Schistosoma infection-associated deficits in educational measures were robust among observational studies, but not among interventional studies. The significance of infection-associated deficits
Bustinduy, Amaya L.; Nkwata, Allan K.; Martinez, Leonardo; Pabalan, Noel; Boivin, Michael J.; King, Charles H.
Background By means of meta-analysis of information from all relevant epidemiologic studies, we examined the hypothesis that Schistosoma infection in school-aged children (SAC) is associated with educational loss and cognitive deficits. Methodology/Principal findings This review was prospectively registered in the PROSPERO database (CRD42016040052). Medline, Biosis, and Web of Science were searched for studies published before August 2016 that evaluated associations between Schistosoma infection and cognitive or educational outcomes. Cognitive function was defined in four domains—learning, memory, reaction time, and innate intelligence. Educational outcome measures were defined as attendance and scholastic achievement. Risk of bias (ROB) was evaluated using the Newcastle-Ottawa quality assessment scale. Standardized mean differences (SMD) and 95% confidence intervals (CI) were calculated to compare cognitive and educational measures for Schistosoma infected /not dewormed vs. uninfected/dewormed children. Sensitivity analyses by study design, ROB, and sequential exclusion of individual studies were implemented. Thirty studies from 14 countries, including 38,992 SAC between 5–19 years old, were identified. Compared to uninfected children and children dewormed with praziquantel, the presence of Schistosoma infection and/or non-dewormed status was associated with deficits in school attendance (SMD = -0.36, 95%CI: -0.60, -0.12), scholastic achievement (SMD = -0.58, 95%CI: -0.96, -0.20), learning (SMD = -0.39, 95%CI: -0.70, -0.09) and memory (SMD = -0.28, 95%CI: -0.52, -0.04) tests. By contrast, Schistosoma-infected/non-dewormed and uninfected/dewormed children were similar with respect to performance in tests of reaction time (SMD = -0.06, 95%CI: -0.42, 0.30) and intelligence (SMD = -0.25, 95%CI: -0.57, 0.06). Schistosoma infection-associated deficits in educational measures were robust among observational studies, but not among interventional studies. The
Hwang-Gu, Shoou-Lian; Gau, Susan Shur-Fen
The literature has suggested timing processing as a potential endophenotype for attention deficit/hyperactivity disorder (ADHD); however, whether the subjective internal clock speed presented by verbal estimation and limited attention capacity presented by time reproduction could be endophenotypes for ADHD is still unknown. We assessed 223 youths with DSM-IV ADHD (age range: 10-17 years), 105 unaffected siblings, and 84 typically developing (TD) youths using psychiatric interviews, intelligence tests, verbal estimation and time reproduction tasks (single task and simple and difficult dual tasks) at 5-second, 12-second, and 17-second intervals. We found that youths with ADHD tended to overestimate time in verbal estimation more than their unaffected siblings and TD youths, implying that fast subjective internal clock speed might be a characteristic of ADHD, rather than an endophenotype for ADHD. Youths with ADHD and their unaffected siblings were less precise in time reproduction dual tasks than TD youths. The magnitude of estimated errors in time reproduction was greater in youths with ADHD and their unaffected siblings than in TD youths, with an increased time interval at the 17-second interval and with increased task demands on both simple and difficult dual tasks versus the single task. Increased impaired time reproduction in dual tasks with increased intervals and task demands were shown in youths with ADHD and their unaffected siblings, suggesting that time reproduction deficits explained by limited attention capacity might be a useful endophenotype of ADHD. PMID:25992899
Furtner, J.; Prayer, D.; Sachs, G.
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.) [de
Wiig, Elisabeth Hemmersam; Nielsen, Niels Peter
Objective: This retrospective study used A Quick Test of Cognitive Speed (AQT) to compare processing speed and efficiency measures by adults with attention-deficit/hyperactivity disorder (ADHD) or non-ADHD psychiatric disorders and healthy controls.
Merker, S.; Reif, A.; Ziegler, G.C.; Weber, H.; Mayer, U.; Ehlis, A.C.; Conzelmann, A.; Johansson, S.; Muller-Reible, C.; Nanda, I.; Haaf, T.; Ullmann, R.; Romanos, M.; Fallgatter, A.J.; Pauli, P.; Strekalova, T.; Jansch, C.; Arias Vasquez, A.; Haavik, J.; Ribases, M.; Ramos-Quiroga, J.A.; Buitelaar, J.K.; Franke, B.; Lesch, K.P.
BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) is a common, highly heritable neurodevelopmental disorder with profound cognitive, behavioral, and psychosocial impairments with persistence across the life cycle. Our initial genome-wide screening approach for copy number variants (CNVs)
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 diagnosed with ADHD completed self-report questionnaires, diagnostic interviews, and clinician-administered symptom rating scales. Statistical mediation analysis was employed and indirect effects assessed using bootstrap analysis and bias-corrected confidence intervals. Controlling for recent negative life events, dysfunctional attitudes and cognitive-behavioral avoidance fully accounted for the variance between ADHD symptoms and depressive symptoms. Each independent variable partially mediated the other in accounting for depression symptoms suggesting overlapping and unique variance. Cognitive-behavioral avoidance, however, was more strongly related to meeting diagnostic criteria for a depressive disorder than were dysfunctional attitudes. Processes that are targeted in cognitive behavior therapy (CBT) for depression were associated with symptoms in adults with ADHD. Current CBT approaches for ADHD incorporate active coping skills and cognitive restructuring and such approaches could be further tailored to address the ADHD-depression comorbidity. PMID:26089578
Full Text Available HIV-associated neurocognitive disorders (HAND affects more than half of persons living with HIV-1/AIDS (PLWHA. Identification of biomarkers representing the cognitive status of PLWHA is a critical step for implementation of successful cognitive, behavioral and pharmacological strategies to prevent onset and progression of HAND. However, the presence of co-morbidity factors in PLWHA, the most common being substance abuse, can prevent the identification of such biomarkers. We have optimized a protocol to profile plasma miRNAs using quantitative RT-qPCR and found a miRNA signature with very good discriminatory ability to distinguish PLWHA with cognitive impairment from those without cognitive impairment. Here, we have evaluated this miRNA signature in PLWHA with alcohol use disorder (AUD at LSU Health Sciences Center (LSUHSC. The results show that AUD is a potential confounding factor for the miRNAs associated with cognitive impairment in PLWHA. Furthermore, we have investigated the miRNA signature associated with cognitive impairment in an independent cohort of PLWHA using plasma samples from the CNS HIV Antiretroviral Therapy Effects Research (CHARTER program. Despite differences between the two cohorts in socioeconomic status, AUD, and likely misuse of illicit or prescription drugs, we validated a miRNA signature for cognitive deficits found at LSUHSC in the CHARTER samples.
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 tested functions was observed in both groups. However, in patients with post-traumatic language processing deficits the degree of recovery of most language functions and some cognitive functions was higher. A significantly greater correlation was revealed within language and cognitive functions, as well as between language functions and other aspects of cognition in patients with post-traumatic language processing deficits than in patients with aphasia following a stroke. Our results show that patients with post-traumatic language processing deficits have a different recovery pattern and a different pattern of correlation between language and cognitive functions compared to patients with aphasia following a stroke. (1) Better understanding of the differences in recovery of language and cognitive functions in patients who have suffered strokes and those who have experienced traumatic brain injury. (2) Better understanding of the relationship between language and cognitive functions in patients with post-traumatic language processing deficits and in patients with aphasia following a stroke. (3) Better understanding of the factors influencing recovery.
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
Steiner, Naomi J; Frenette, Elizabeth C; Rene, Kirsten M; Brennan, Robert T; Perrin, Ellen C
To evaluate the efficacy of 2 computer attention training systems administered in school for children with attention-deficit hyperactivity disorder (ADHD). Children in second and fourth grade with a diagnosis of ADHD (n = 104) were randomly assigned to neurofeedback (NF) (n = 34), cognitive training (CT) (n = 34), or control (n = 36) conditions. A 2-point growth model assessed change from pre-post intervention on parent reports (Conners 3-Parent [Conners 3-P]; Behavior Rating Inventory of Executive Function [BRIEF] rating scale), teacher reports (Swanson, Kotkin, Agler, M-Flynn and Pelham scale [SKAMP]; Conners 3-Teacher [Conners 3-T]), and systematic classroom observations (Behavioral Observation of Students in Schools [BOSS]). Paired t tests and an analysis of covariance assessed change in medication. Children who received NF showed significant improvement compared with those in the control condition on the Conners 3-P Attention, Executive Functioning and Global Index, on all BRIEF summary indices, and on BOSS motor/verbal off-task behavior. Children who received CT showed no improvement compared to the control condition. Children in the NF condition showed significant improvements compared to those in the CT condition on Conners 3-P Executive Functioning, all BRIEF summary indices, SKAMP Attention, and Conners 3-T Inattention subscales. Stimulant medication dosage in methylphenidate equivalencies significantly increased for children in the CT (8.54 mg) and control (7.05 mg) conditions but not for those in the NF condition (0.29 mg). Neurofeedback made greater improvements in ADHD symptoms compared to both the control and CT conditions. Thus, NF is a promising attention training treatment intervention for children with ADHD.
Brown, Jeffrey A; Dalecki, Marc; Hughes, Cindy; Macpherson, Alison K; Sergio, Lauren E
The ability to perform visually-guided motor tasks requires the transformation of visual information into programmed motor outputs. When the guiding visual information does not align spatially with the motor output, the brain processes rules to integrate the information for an appropriate motor response. Here, we look at how performance on such tasks is affected in young adult athletes with concussion history. Participants displaced a cursor from a central to peripheral targets on a vertical display by sliding their finger along a touch sensitive screen in one of two spatial planes. The addition of a memory component, along with variations in cursor feedback increased task complexity across conditions. Significant main effects between participants with concussion history and healthy controls without concussion history were observed in timing and accuracy measures. Importantly, the deficits were distinctly more pronounced for participants with concussion history compared to healthy controls, especially when the brain had to control movements having two levels of decoupling between vision and action. A discriminant analysis correctly classified athletes with a history of concussion based on task performance with an accuracy of 94 %, despite the majority of these athletes being rated asymptomatic by current standards. These findings correspond to our previous work with adults at risk of developing dementia, and support the use of cognitive motor integration as an enhanced assessment tool for those who may have mild brain dysfunction. Such a task may provide a more sensitive metric of performance relevant to daily function than what is currently in use, to assist in return to play/work/learn decisions.
Zadikoff, Cindy; Fox, Susan H.; Tang-Wai, David F.; Thomsen, Teri; de Bie, Rob M. A.; Wadia, Pettarusup; Miyasaki, Janis; Duff-Canning, Sarah; Lang, Anthony E.; Marras, Connie
Dementia is an important and increasingly recognized problem in Parkinson's disease (PD). The mini-mental state examination (MMSE) often fails to detect early cognitive decline. The Montreal cognitive assessment (MoCA) is a brief tool developed to detect mild cognitive impairment that assesses a
Carrigan, Nicole; Barkus, Emma; Ong, Adriel; Wei, Maryann
Individuals high on schizotypy complain of increased cognitive failures in everyday life. However, the neuropsychological performance of this group does not consistently indicate underlying ability deficits. It is possible that current neuropsychological tests lack ecological validity. Given the increased affective reactivity of high schizotypes, they may be more sensitive to emotional content interfering with cognitive ability. This study sought to explore whether an affective n-back working memory task would elicit impaired performance in schizotypy, echoing complaints concerning real world cognition. 127 healthy participants completed self-report measures of schizotypy and cognitive failures and an affective n-back working memory task. This task was varied across three levels of load (1- to 3-back) and four types of stimulus emotion (neutral, fearful, happy, sad). Differences between high (n=39) and low (n=48) schizotypy groups on performance outcomes of hits and false alarms were examined, with emotion and load as within-groups variables. As expected, high schizotypes reported heightened vulnerability to cognitive failures. They also demonstrated a relative working memory impairment for emotional versus neutral stimuli, whereas low schizotypes did not. High schizotypes performed most poorly in response to fearful stimuli. For false alarms, there was an interaction between schizotypy, load, and emotion, such that high schizotypy was associated with deficits in response to fearful stimuli only at higher levels of task difficulty. Inclusion of self-reported cognitive failures did not account for this. These findings suggest that the "gap" between subjective and objective cognition in schizotypy may reflect the heightened emotional demands associated with cognitive functioning in the real world, although other factors also seem to play a role. There is a need to improve the ecological validity of objective assessments, whilst also recognizing that self
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.
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. Copyright © 2015 Elsevier B.V. and ECNP. All rights reserved.
Reimers, Tonny Solveig; Ehrenfels, Susanne; Mortensen, Erik Lykke
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....
Pu, Shenghong; Setoyama, Shiori; Noda, Takamasa
The role of cognitive function in suicidal ideation in patients with major depressive disorder (MDD) has not been adequately explored. This research sought to measure the relationship between suicidal ideation and cognitive function. Therefore, in this study, the association between cognitive function and suicidal ideation in patients with MDD was assessed. Cognitive function was evaluated in 233 patients with MDD using the Japanese version of the Brief Assessment of Cognition in Schizophreni...
Lopez, Pablo Luis; Torrente, Fernando Manuel; Ciapponi, Agustín; Lischinsky, Alicia Graciela; Cetkovich-Bakmas, Marcelo; Rojas, Juan Ignacio; Romano, Marina; Manes, Facundo F
Attention deficit hyperactivity disorder (ADHD) is a developmental condition characterised by symptoms of inattention, hyperactivity and impulsivity, along with deficits in executive function, emotional regulation and motivation. The persistence of ADHD in adulthood is a serious clinical problem.ADHD significantly affects social interactions, study and employment performance.Previous studies suggest that cognitive-behavioural therapy (CBT) could be effective in treating adults with ADHD, especially when combined with pharmacological treatment. CBT aims to change the thoughts and behaviours that reinforce harmful effects of the disorder by teaching people techniques to control the core symptoms. CBT also aims to help people cope with emotions, such as anxiety and depression, and to improve self-esteem. To assess the effects of cognitive-behavioural-based therapy for ADHD in adults. In June 2017, we searched CENTRAL, MEDLINE, Embase, seven other databases and three trials registries. We also checked reference lists, handsearched congress abstracts, and contacted experts and researchers in the field. Randomised controlled trials (RCTs) evaluating any form of CBT for adults with ADHD, either as a monotherapy or in conjunction with another treatment, versus one of the following: unspecific control conditions (comprising supportive psychotherapies, no treatment or waiting list) or other specific interventions. We used the standard methodological procedures suggested by Cochrane. We included 14 RCTs (700 participants), 13 of which were conducted in the northern hemisphere and 1 in Australia.Primary outcomes: ADHD symptomsCBT versus unspecific control conditions (supportive psychotherapies, waiting list or no treatment)- CBT versus supportive psychotherapies: CBT was more effective than supportive therapy for improving clinician-reported ADHD symptoms (1 study, 81 participants; low-quality evidence) but not for self-reported ADHD symptoms (SMD -0.16, 95% CI -0.52 to 0
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…
Li, Fang; Yan, Chao-Qun; Lin, Li-Ting; Li, Hui; Zeng, Xiang-Hong; Liu, Yi; Du, Si-Qi; Zhu, Wen; Liu, Cun-Zhi
Decreased cognition is recognized as one of the most severe and consistent behavioral impairments in dementia. Experimental studies have reported that acupuncture may improve cognitive deficits, relieve vascular dementia (VD) symptoms, and increase cerebral perfusion and electrical activity. Multi-infarction dementia was modeled in rats with 3% microemboli saline suspension. Two weeks after acupuncture at Zusanli (ST36), all rats were subjected to a hidden platform trial to test their 3-day spatial memory using the Morris water maze test. To estimate the numbers of pyramidal neuron, astrocytes, and synaptic boutons in hippocampal CA1 area, we adopted an unbiased stereology method to accurately sample and measure the size of cells. We found that acupuncture at ST36 significantly decreased the escape latency of VD rats. In addition, acupuncture significantly increased the pyramidal neuron number in hippocampal CA1 area (P area in any of the groups (P > 0.05). These findings suggest that acupuncture may improve cognitive deficits and increase pyramidal neuron number of hippocampal CA1 area in VD rats.
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.
Bowie, Christopher R; Best, Michael W; Depp, Colin; Mausbach, Brent T; Patterson, Thomas L; Pulver, Ann E; Harvey, Philip D
Schizophrenia and bipolar disorder overlap considerably. Schizophrenia is a primary psychotic disorder, whereas approximately half of people with bipolar disorder will experience psychosis. In this study, we examined the extent to which cognitive and functional impairments are related to the presence and history of psychosis across the two disorders. A total of 633 participants with bipolar disorder I, schizophrenia, and schizoaffective disorder were recruited for a study on the genetics of cognition and functioning in bipolar disorder and schizophrenia. Participants were classified into five groups: bipolar disorder with current psychosis (N = 30), bipolar disorder with a history of psychosis (N = 162), bipolar disorder with no history of psychosis (N = 92), schizophrenia with current psychosis (N = 245), and schizophrenia with past psychosis (N = 104). Cognitive profiles of all groups were similar in pattern; however, both current psychosis (P bipolar disorder and schizophrenia experienced similar impairments in real-world functioning if they were experiencing current psychosis (P = .32). The presence of active psychosis is an important cross-diagnostic factor in cognition and functioning in both schizophrenia and bipolar disorder. Characterization and treatment of cognition and functional deficits in bipolar disorder should consider the effects of both current and history of psychosis. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Jahrling, Jordan B; Lin, Ai-Ling; DeRosa, Nicholas; Hussong, Stacy A; Van Skike, Candice E; Girotti, Milena; Javors, Martin; Zhao, Qingwei; Maslin, Leigh Ann; Asmis, Reto; Galvan, Veronica
We recently showed that mTOR attenuation blocks progression and abrogates established cognitive deficits in Alzheimer's disease (AD) mouse models. These outcomes were associated with the restoration of cerebral blood flow (CBF) and brain vascular density (BVD) resulting from relief of mTOR inhibition of NO release. Recent reports suggested a role of mTOR in atherosclerosis. Because mTOR drives aging and vascular dysfunction is a universal feature of aging, we hypothesized that mTOR may contribute to brain vascular and cognitive dysfunction associated with atherosclerosis. We measured CBF, BVD, cognitive function, markers of inflammation, and parameters of cardiovascular disease in LDLR -/- mice fed maintenance or high-fat diet ± rapamycin. Cardiovascular pathologies were proportional to severity of brain vascular dysfunction. Aortic atheromas were reduced, CBF and BVD were restored, and cognitive dysfunction was attenuated potentially through reduction in systemic and brain inflammation following chronic mTOR attenuation. Our studies suggest that mTOR regulates vascular integrity and function and that mTOR attenuation may restore neurovascular function and cardiovascular health. Together with our previous studies in AD models, our data suggest mTOR-driven vascular damage may be a mechanism shared by age-associated neurological diseases. Therefore, mTOR attenuation may have promise for treatment of cognitive impairment in atherosclerosis.
Nair, Deepti; Ramesh, Vijay; Li, Richard C; Schally, Andrew V; Gozal, David
Intermittent hypoxia (IH) during sleep, such as occurs in obstructive sleep apnea (OSA), leads to degenerative changes in the hippocampus, and is associated with spatial learning deficits in adult mice. In both patients and murine models of OSA, the disease is associated with suppression of growth hormone (GH) secretion, which is actively involved in the growth, development, and function of the central nervous system (CNS). Recent work showed that exogenous GH therapy attenuated neurocognitive deficits elicited by IH during sleep in rats. Here, we show that administration of the Growth Hormone Releasing Hormone (GHRH) agonist JI-34 attenuates IH-induced neurocognitive deficits, anxiety, and depression in mice along with reduction in oxidative stress markers such as MDA and 8-hydroxydeoxyguanosine, and increases in hypoxia inducible factor-1α DNA binding and up-regulation of insulin growth factor-1 and erythropoietin expression. In contrast, treatment with a GHRH antagonist (MIA-602) during intermittent hypoxia did not affect any of the IH-induced deleterious effects in mice. Thus, exogenous GHRH administered as the formulation of a GHRH agonist may provide a viable therapeutic intervention to protect IH-vulnerable brain regions from OSA-associated neurocognitive dysfunction. Sleep apnea, characterized by chronic intermittent hypoxia (IH), is associated with substantial cognitive and behavioral deficits. Here, we show that administration of a GHRH agonist (JI-34) reduces oxidative stress, increases both HIF-1α nuclear binding and downstream expression of IGF1 and erythropoietin (EPO) in hippocampus and cortex, and markedly attenuates water maze performance deficits in mice exposed to intermittent hypoxia during sleep. © 2013 International Society for Neurochemistry.
Biradar, S M; Joshi, H; Chheda, T K
Biochanin-A (BCA), a potent phytoconstituent, has been previously used as an antitumour, a dopaminergic neuron protective agent, an antioxidant, an anticholinergic and on other pharmacological activities including neuroprotection. The present study was aimed to evaluate the behavioural and neurochemical evidence of BCA in cognitive-deficit mice in scopolamine challenged and natural aged-induced amnesia models in young and aged mice, respectively. BCA has exhibited decrease in the transfer latency and increase in step through latency significantly (p 0.05), BCA 10 mg kg(-1) (p betterment of Alzheimer's disease.
Henningsen, Kim; Andreasen T., Jesper; Bouzinova, Elena V.
in the spontaneous alternation test, possibly reflecting a deficit in working memory. This effect was independent of whether the stressed rats were anhedonic-like or stress-resilient as measured by their sucrose intake. CMS did not influence performance in passive avoidance and auditory cued fear conditioning......The chronic mild stress (CMS) protocol is widely used to evoke depressive-like behaviours in laboratory rats. The aim of the present study was to examine the effects of chronic stress on cognitive performance. About 70% of rats exposed to 7 weeks of chronic mild stress showed a gradual reduction...... in consumption of a sucrose solution, indicating an anhedonic-like state. The remaining rats did not reduce their sucrose intake, but appeared resilient to the stress-induced effects on sucrose intake. Cognitive profiling of the CMS rats revealed that chronic stress had a negative effect on performance...
Beaunieux, Hélène; Hubert, Valérie; Pitel, Anne Lise; Desgranges, Béatrice; Eustache, Francis
Cognitive procedural learning is characterized by three phases, each involving distinct processes. Considering the implication of the episodic memory in the first cognitive stage, the impairment of this memory system might be responsible for a slowing down of the cognitive procedural learning dynamics in the course of aging. Performances of massed cognitive procedural learning were evaluated in older and younger participants using the Tower of Toronto task. Nonverbal intelligence and psychomotor abilities were used to analyze procedural dynamics, while episodic memory and working memory were assessed to measure their respective contributions to learning strategies. This experiment showed that older participants did not spontaneously invoke episodic memory and presented a slowdown in the cognitive procedural learning associated with a late involvement of working memory. These findings suggest that the slowdown in the cognitive procedural learning may be linked with the implementation of different learning strategies less involving episodic memory in older subjects. PMID:18654928
Full Text Available Aim and background: One of the most important psychological disorders after stroke is depression, which leads to reduced quality of life, optimal rehabilitation failure, loss of cognitive tasks and decrease in the recovery process. In this research, relation between patterns of depression and cognitive, motor and function deficits in people with chronic stroke was studied. Methods and materials: In a pilot cross-sectional study, 40 patients with chronic stroke (more than 6 months were enrolled. Depression (Beck Depression Inventory, cognition (attention test TMT-A & B and Wechsler memory, motor (Motorcity index, basic activities of daily living (Barthel scale and instrumental activities of daily living (Lawton scale were evaluated. Results: The results of the study revealed a significant positive correlation between post stroke depression and verbal memory (r=0.440،P<.05, attention (r=0.615،P<.05, motor function(r-0.368،P<.05, independence in basic activities of daily living (r=0.781،P<.05 and instrumental activities of daily living (r=0.741, P<.05. Conclusion: According to the findings, further studies of factors affecting post stroke depression (PSD clinical and practical aspects are necessary. Cognitive rehabilitation programs with motor rehabilitation can decrease depression and gain independence in activities of daily living and more participation in society activities.
Shema-Shiratzky, Shirley; Brozgol, Marina; Cornejo-Thumm, Pablo; Geva-Dayan, Karen; Rotstein, Michael; Leitner, Yael; Hausdorff, Jeffrey M; Mirelman, Anat
To examine the feasibility and efficacy of a combined motor-cognitive training using virtual reality to enhance behavior, cognitive function and dual-tasking in children with Attention-Deficit/Hyperactivity Disorder (ADHD). Fourteen non-medicated school-aged children with ADHD, received 18 training sessions during 6 weeks. Training included walking on a treadmill while negotiating virtual obstacles. Behavioral symptoms, cognition and gait were tested before and after the training and at 6-weeks follow-up. Based on parental report, there was a significant improvement in children's social problems and psychosomatic behavior after the training. Executive function and memory were improved post-training while attention was unchanged. Gait regularity significantly increased during dual-task walking. Long-term training effects were maintained in memory and executive function. Treadmill-training augmented with virtual-reality is feasible and may be an effective treatment to enhance behavior, cognitive function and dual-tasking in children with ADHD.
Full Text Available Michal Goetz,1 Jaroslava Paulasova Schwabova,2 Zdenek Hlavka,3 Radek Ptacek,4 Craig BH Surman5 1Department of Child Psychiatry, Second Faculty of Medicine, Motol University Hospital, 2Department of Neurology, 3Department of Statistics, 4Department of Psychiatry, Charles University, Prague, Czech Republic; 5Department of Psychiatry, Harvard Medical School, Boston, MA, USA Background: Attention-deficit hyperactivity disorder (ADHD is linked to the presence of motor deficiencies, including balance deficits. The cerebellum serves as an integrative structure for balance control and is also involved in cognition, including timing and anticipatory regulation. Cerebellar development may be delayed in children and adolescents with ADHD, and inconsistent reaction time is commonly seen in ADHD. We hypothesized that dynamic balance deficits would be present in children with ADHD and they would correlate with attention and cerebellar functions. Methods: Sixty-two children with ADHD and no other neurological conditions and 62 typically developing (TD children were examined with five trials of the Phyaction Balance Board, an electronic balancing platform. Cerebellar clinical symptoms were evaluated using an international ataxia rating scale. Conners’ Continuous Performance Test was used to evaluate patterns of reaction. Results: Children with ADHD had poorer performance on balancing tasks, compared to TD children (P<0.001. They exhibited significantly greater sway amplitudes than TD children (P<0.001 in all of the five balancing trials. The effect size of the difference between the groups increased continuously from the first to the last trial. Balance score in both groups was related to the variation in the reaction time, including reaction time standard error (r =0.25; P=0.0409, respectively, r =0.31; P=0.0131 and Variability of Standard Error (r =0.28; P=0.0252, respectively, r =0.41; P<0.001. The burden of cerebellar symptoms was strongly related to
Cortese, Samuele; Ferrin, Maite; Brandeis, Daniel; Buitelaar, Jan; Daley, David; Dittmann, Ralf W.; Holtmann, Martin; Santosh, Paramala; Stevenson, Jim; Stringaris, Argyris; Zuddas, Alessandro; Sonuga-Barke, Edmund J.S.
Objective The authors performed meta-analyses of randomized controlled trials to examine the effects of cognitive training on attention-deficit/hyperactivity disorder (ADHD) symptoms, neuropsychological deficits, and academic skills in children/adolescents with ADHD. Method The authors searched Pubmed, Ovid, Web of Science, ERIC, and CINAHAL databases through May 18, 2014. Data were aggregated using random-effects models. Studies were evaluated with the Cochrane risk of bias tool. Results Sixteen of 695 nonduplicate records were analyzed (759 children with ADHD). When all types of training were considered together, there were significant effects on total ADHD (standardized mean difference [SMD] = 0.37, 95% CI = 0.09–0.66) and inattentive symptoms (SMD = 0.47, 95% CI = 0.14–0.80) for reports by raters most proximal to the treatment setting (i.e., typically unblinded). These figures decreased substantially when the outcomes were provided by probably blinded raters (ADHD total: SMD = 0.20, 95% CI = 0.01–0.40; inattention: SMD = 0.32, 95% CI = −0.01 to 0.66). Effects on hyperactivity/impulsivity symptoms were not significant. There were significant effects on laboratory tests of working memory (verbal: SMD = 0.52, 95% CI = 0.24–0.80; visual: SMD = 0.47, 95% CI = 0.23–0.70) and parent ratings of executive function (SMD = 0.35, 95% CI = 0.08–0.61). Effects on academic performance were not statistically significant. There were no effects of working memory training, specifically on ADHD symptoms. Interventions targeting multiple neuropsychological deficits had large effects on ADHD symptoms rated by most proximal assessors (SMD = 0.79, 95% CI = 0.46–1.12). Conclusion Despite improving working memory performance, cognitive training had limited effects on ADHD symptoms according to assessments based on blinded measures. Approaches targeting multiple neuropsychological processes may optimize the transfer of effects from cognitive deficits to
Sokal, Michael M
Despite widespread interest in individual life histories, few biographies of scientists make use of insights derived from psychology, another discipline that studies people, their thoughts, and their actions. This essay argues that recent theoretical work in psychology and tools developed for clinical psychological practice can help biographical historians of science create and present fuller portraits of their subjects' characters and temperaments and more nuanced analyses of how these traits helped shape their subjects' scientific work. To illustrate this thesis, the essay examines the early career of James McKeen Cattell--an influential late nineteenth- and early twentieth-century experimental psychologist--through a lens offered by psychology and argues that Cattell's actual laboratory practices derived from an "accommodation" to a long-standing "cognitive deficit." These practices in turn enabled Cattell to achieve more precise experimental results than could any of his contemporaries; and their students readily adopted them, along with their behavioral implications. The essay concludes that, in some ways, American psychology's early twentieth-century move toward a behavioral understanding of psychological phenomena can be traced to Cattell's personal cognitive deficit. It closes by reviewing several "remaining general questions" that this thesis suggests.
Miguel, Carmen S; Martins, Paula A; Moleda, Nathalya; Klein, Margarete; Chaim-Avancini, Tiffany; Gobbo, Maria A; Alves, Tania M; Silva, Maria A; Louzã, Mario R
Substance use disorder (SUD) is a common comorbidity in adults with attention deficit-hyperactivity disorder (ADHD). However,there have been few studies on cognitive profiles of these patients. Impulsivity is also commonly increased in both disorders. The central aim of this study was to compare cognition and impulsivity in subjects who had ADHD and cocaine dependence (ADHD+COC group) to those with ADHD only (ADHD-noSUD group). We hypothesized that the ADHD+COC group would show more marked cognitive dysfunction and greater impulsivity than their counterparts with ADHD only. A total of 70 adult patients diagnosed with ADHD according to (DSM-IV-TR) criteria were enrolled; 36 with ADHD+COC and 34 with ADHD-noSUD. All study participants were evaluated with a sociodemographic questionnaire; the Mini International Neuropsychiatric Interview; the Adult ADHD Self-Report Scale; the Addiction Severity Index; the Alcohol, Smoking and Substance Involvement Screening Test; the Barratt Impulsiveness Scale; and a comprehensive neurocognitive battery. Compared to individuals with ADHD-noSUD, ADHD+COC individuals had significantly lower mean IQ and higher motor impulsivity. On average, the ADHD+COC group also performed more poorly on tasks assessing verbal skills, vigilance, implicit learning during decision making, and ADHD-noSUD performed more poorly on selective attention, information processing, and visual search. Our results support the integrative theory of ADHD based on the cognitive and affective neuroscience model, and suggests that ADHD-noSUD patients have impairments in cognitive regulation, while ADHD+COC patients have impairments in both cognitive and affective regulation. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.
Ibáñez, Agustin; Petroni, Agustin; Urquina, Hugo; Torrente, Fernando; Torralva, Teresa; Hurtado, Esteban; Guex, Raphael; Blenkmann, Alejandro; Beltrachini, Leandro; Muravchik, Carlos; Baez, Sandra; Cetkovich, Marcelo; Sigman, Mariano; Lischinsky, Alicia; Manes, Facundo
Although it has been shown that adults with attention-deficit hyperactivity disorder (ADHD) have impaired social cognition, no previous study has reported the brain correlates of face valence processing. This study looked for behavioral, neuropsychological, and electrophysiological markers of emotion processing for faces (N170) in adult ADHD compared to controls matched by age, gender, educational level, and handedness. We designed an event-related potential (ERP) study based on a dual valence task (DVT), in which faces and words were presented to test the effects of stimulus type (faces, words, or face-word stimuli) and valence (positive versus negative). Individual signatures of cognitive functioning in participants with ADHD and controls were assessed with a comprehensive neuropsychological evaluation, including executive functioning (EF) and theory of mind (ToM). Compared to controls, the adult ADHD group showed deficits in N170 emotion modulation for facial stimuli. These N170 impairments were observed in the absence of any deficit in facial structural processing, suggesting a specific ADHD impairment in early facial emotion modulation. The cortical current density mapping of N170 yielded a main neural source of N170 at posterior section of fusiform gyrus (maximum at left hemisphere for words and right hemisphere for faces and simultaneous stimuli). Neural generators of N170 (fusiform gyrus) were reduced in ADHD. In those patients, N170 emotion processing was associated with performance on an emotional inference ToM task, and N170 from simultaneous stimuli was associated with EF, especially working memory. This is the first report to reveal an adult ADHD-specific impairment in the cortical modulation of emotion for faces and an association between N170 cortical measures and ToM and EF.
Buunk, Anne M; Groen, Rob J M; Veenstra, Wencke S; Metzemaekers, Joannes; van der Hoeven, Johannes H; van Dijk, J Marc C; Spikman, Jacoba M
OBJECTIVE: The authors' aim was to investigate cognitive outcome in patients with aneurysmal and angiographically negative subarachnoid hemorrhage (aSAH and anSAH), by comparing them to healthy controls and to each other. Besides investigating cognitive functions as memory and attention, they
White, Susan W.; Albano, Anne Marie; Johnson, Cynthia R.; Kasari, Connie; Ollendick, Thomas; Klin, Ami; Oswald, Donald; Scahill, Lawrence
Anxiety is a common co-occurring problem among young people with autism spectrum disorders (ASD). Characterized by deficits in social interaction, communication problems, and stereotyped behavior and restricted interests, this group of disorders is more prevalent than previously realized. When present, anxiety may compound the social deficits of young people with ASD. Given the additional disability and common co-occurrence of anxiety in ASD, we developed a manual-based cognitive-behavioral t...
Machts, Judith; Bittner, Verena; Kasper, Elisabeth; Schuster, Christina; Prudlo, Johannes; Abdulla, Susanne; Kollewe, Katja; Petri, Susanne; Dengler, Reinhard; Heinze, Hans-Jochen; Vielhaber, Stefan; Schoenfeld, Mircea A; Bittner, Daniel M
Background Recent work suggests that ALS and frontotemporal dementia can occur together and share at least in part the same underlying pathophysiology. However, it is unclear at present whether memory deficits in ALS stem from a temporal lobe dysfunction, or are rather driven by frontal executive dysfunction. In this study we sought to investigate the nature of memory deficits by analyzing the neuropsychological performance of 40 ALS patients in comparison to 39 amnestic mild cognitive impair...
Spikman, Jacoba M.; Timmerman, Marieke E.; Milders, Maarten V.; Veenstra, Wencke S.; van der Naalt, Joukje
Impairments in social behavior are frequently found in moderate to severe traumatic brain injury (TBI) patients and are associated with an unfavorable outcome with regard to return to work and social reintegration. Neuropsychological tests measuring aspects of social cognition are thought to be
Gehring, K.; Aaronson, N.K.; Taphoorn, M.J.B.; Sitskoorn, M.M.
This series of articles for rehabilitation in practice aims to cover a knowledge element of the rehabilitation medicine curriculum. Nevertheless they are intended to be of interest to a multidisciplinary audience. The competency addressed in this article is cognitive rehabilitation.Background: There
Full Text Available We examined an idea that short-term cognition is transiently affected by a state of confusion in Zn2+ transport system due to a local increase in amyloid-β (Aβ concentration. A single injection of Aβ (25 pmol into the dentate gyrus affected dentate gyrus long-term potentiation (LTP 1 h after the injection, but not 4 h after the injection. Simultaneously, 1-h memory of object recognition was affected when the training was performed 1 h after the injection, but not 4 h after the injection. Aβ-mediated impairments of LTP and memory were rescued in the presence of zinc chelators, suggesting that Zn2+ is involved in Aβ action. When Aβ was injected into the dentate gyrus, intracellular Zn2+ levels were increased only in the injected area in the dentate gyrus, suggesting that Aβ induces the influx of Zn2+ into cells in the injected area. When Aβ was added to hippocampal slices, Aβ did not increase intracellular Zn2+ levels in the dentate granule cell layer in ACSF without Zn2+, but in ACSF containing Zn2+. The increase in intracellular Zn2+ levels was inhibited in the presence of CaEDTA, an extracellular zinc chelator, but not in the presence of CNQX, an AMPA receptor antagonist. The present study indicates that Aβ-mediated Zn2+ influx into dentate granule cells, which may occur without AMPA receptor activation, transiently induces a short-term cognitive deficit. Extracellular Zn2+ may play a key role for transiently Aβ-induced cognition deficits.
Takeda, Atsushi; Nakamura, Masatoshi; Fujii, Hiroaki; Uematsu, Chihiro; Minamino, Tatsuya; Adlard, Paul A; Bush, Ashley I; Tamano, Haruna
We examined an idea that short-term cognition is transiently affected by a state of confusion in Zn2+ transport system due to a local increase in amyloid-β (Aβ) concentration. A single injection of Aβ (25 pmol) into the dentate gyrus affected dentate gyrus long-term potentiation (LTP) 1 h after the injection, but not 4 h after the injection. Simultaneously, 1-h memory of object recognition was affected when the training was performed 1 h after the injection, but not 4 h after the injection. Aβ-mediated impairments of LTP and memory were rescued in the presence of zinc chelators, suggesting that Zn2+ is involved in Aβ action. When Aβ was injected into the dentate gyrus, intracellular Zn2+ levels were increased only in the injected area in the dentate gyrus, suggesting that Aβ induces the influx of Zn2+ into cells in the injected area. When Aβ was added to hippocampal slices, Aβ did not increase intracellular Zn2+ levels in the dentate granule cell layer in ACSF without Zn2+, but in ACSF containing Zn2+. The increase in intracellular Zn2+ levels was inhibited in the presence of CaEDTA, an extracellular zinc chelator, but not in the presence of CNQX, an AMPA receptor antagonist. The present study indicates that Aβ-mediated Zn2+ influx into dentate granule cells, which may occur without AMPA receptor activation, transiently induces a short-term cognitive deficit. Extracellular Zn2+ may play a key role for transiently Aβ-induced cognition deficits.
Hjordt, Liv Vadskjær; Stenbæk, Dea Siggaard; Ozenne, Brice
Modalities Test (SDMT) and the Simple Reaction Time (SRT) twice; in summer and in winter. Compared to controls, SAD individuals showed significant season-independent impairments in tasks measuring working memory (LNS), cognitive processing speed (SDMT) and motor speed (SRT). In SAD individuals, cognitive...... processing speed was significantly negatively associated with the seasonal change in SAD depressive symptoms. We present novel evidence that in SAD individuals, working memory, cognitive processing- and motor speed is not only impaired in the winter but also in the summer. This suggests that certain...
Peyroux, Elodie; Rigard, Caroline; Saucourt, Guillaume; Poisson, Alice; Plasse, Julien; Franck, Nicolas; Demily, Caroline
Social cognitive impairments are core features in 22q11.2 deletion syndrome (22q11.2DS) and schizophrenia (SCZ). Indeed, adults with 22q.11.2 DS often have poorer social competence as well as poorer performance on measures of social cognitive skills (emotion recognition and theory of mind, ToM) compared with typically developing people. However, studies comparing specific social cognitive components in 22q11.2DS and SCZ have not yet been widely conducted. In this study we compared performances of 22q11.2DS and SCZ on both facial emotion recognition and ToM. Patients with 22q11.2DS (n = 18) and matched SCZ patients were recruited. After neuropsychological testing, the facial emotion recognition test assessed the patients' ability to recognize six basic, universal emotions (joy, anger, sadness, fear, disgust, and contempt). The Versailles-situational intentional reading evaluated ToM with six scenes from movies showing characters in complex interactions (involving hints, lies, and indirect speech). We show that 22q11.2DS exhibited significantly lower performance in emotion recognition than SCZ patients did, especially for disgust, contempt, and fear. This impairment seems to be a core cognitive phenotype in 22q11.2DS, regardless of the presence of SCZ symptoms. Concerning ToM, our results may highlight the same impairment level in 22q11.2DS and SCZ but require to be replicated in a larger cohort. Our results document the existence of threshold social cognitive deficits distinguishing 22q11.2DS from SCZ. © 2018 John Wiley & Sons Australia, Ltd.
Peralta, Gabriela P; Forns, Joan; García de la Hera, Manuela; González, Llúcia; Guxens, Mònica; López-Vicente, Mónica; Sunyer, Jordi; Garcia-Aymerich, Judith
To analyze associations between time spent sleeping, watching TV, engaging in cognitively stimulating activities, and engaging in physical activity, all at 4 years, and (1) attention-deficit/hyperactivity disorder (ADHD) symptoms and (2) behavior problems, both assessed at 7 years, in ADHD-free children at baseline. In total, 817 participants of the Infancia y Medio Ambiente birth cohort, without ADHD at baseline, were included. At the 4-year follow-up, parents reported the time that their children spent sleeping, watching TV, engaging in cognitively stimulating activities, and engaging in physical activity. At the 7-year follow-up, parents completed the Conners' Parent Rating Scales and the Strengths and Difficulties Questionnaire, which measure ADHD symptoms and behavior problems, respectively. Negative binomial regression models were used to assess associations between the activities at 4 years and ADHD symptoms and behavior problems at 7 years. Children (48% girls) spent a median (p25-p75) of 10 (10-11) hours per day sleeping, 1.5 (0.9-2) hours per day watching TV, 1.4 (0.9-1.9) hours per day engaging in cognitively stimulating activities, and 1.5 (0.4-2.3) hours per day engaging in physical activity. Longer sleep duration (>10 hours per day) was associated with a lower ADHD symptom score (adjusted incidence rate ratio = 0.97, 95% confidence interval, 0.95-1.00). Longer time spent in cognitively stimulating activities (>1 hours per day) was associated with lower scores of both ADHD symptoms (0.96, 0.94-0.98) and behavior problems (0.89, 0.83-0.97). Time spent watching TV and engaging in physical activity were not associated with either outcomes. A shorter sleep duration and less time spent in cognitively stimulating activities were associated with an increased risk of developing ADHD symptoms and behavior problems.
Full Text Available 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.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.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 responsible for Internet game addiction. The assessment of
Schleiger, Emma; Sheikh, Nabeel; Rowland, Tennille; Wong, Andrew; Read, Stephen; Finnigan, Simon
This study analysed correlations between post-stroke, quantitative electroencephalographic (QEEG) indices, and cognition-specific, functional outcome measures. Results were compared between QEEG indices calculated from the standard 19 versus 4 frontal (or 4 posterior) electrodes to assess the feasibility and efficacy of employing a reduced electrode montage. Resting-state EEG was recorded at the bedside within 62-101 h after onset of symptoms of middle cerebral artery, ischaemic stroke (confirmed radiologically). Relative power for delta, theta, alpha and beta, delta/alpha ratio (DAR) and pairwise-derived brain symmetry index (pdBSI) were averaged; over all electrodes (global), over F3, F4, F7, F8 (frontal) and P3, P4, T5, T6 (posterior). The functional independence measure and functional assessment measure (FIM-FAM) was administered at mean 105 days post-stroke. Total (30 items) and cognition-specific (5 items) FIM-FAM scores were correlated with QEEG indices using Spearman's coefficient, with a Bonferroni correction. Twenty-five patients were recruited, 4 died within 3 months and 1 was lost to follow-up. Hence 20 cases (10 female; 9 left hemisphere; mean age 68 years, range 38-84) were analysed. Two QEEG indices demonstrated highly-significant correlations with cognitive outcomes: frontal DAR (ρ = -0.664, p ≤ 0.001) and global, relative alpha power (ρ = 0.67, p ≤ 0.001). After correction there were no other significant correlations. Alpha activity - particularly frontally - may index post-stroke attentional capacity, which appears to be a key determinant of functional and cognitive outcomes. Likewise frontal delta pathophysiology influences such outcomes. Pending further studies, DAR from 4 frontal electrodes may inform early screening for post-MCA stroke cognitive deficits, and thereby, clinical decisions. Copyright © 2014 Elsevier B.V. All rights reserved.
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 ...
Full Text Available Objectives. The Cognitive Performance Test (CPT is a functional assessment for persons with dementia. The study purpose was to evaluate the reliability, discriminant, and concurrent validity of the CPT. Method. The CPT was tested against other measures of cognition (Standardized Mini Mental Status Exam (SMMSE and Assessment of Motor and Process Skills-Process scale (AMPS-Process. Participants were persons 65 years and older admitted to a geriatric rehabilitation unit (n=47. Results. The CPT correlated moderately with measures of cognition (SMMSE r=0.47, AMPS-Process r=0.53, P<0.01, and ADL burden of care (FIM r=0.32, P<0.05. Scores were not affected by age, sex, years of education, motor skills, or comorbidities. The CPT differentiated between impaired and unimpaired individuals differently from other measures. Conclusion. While CPT appears related to other measures of cognition, test interpretation requires noting the variability between CPT scores and those measures.
Maria Luíza de Medeiros Rêgo
Full Text Available Abstract Heart Failure is a clinical syndrome prevalent throughout the world and a major contribution to mortality of cardiac patients in Brazil. In addition, this pathology is strongly related to cerebral dysfunction, with a high prevalence of cognitive impairment. Many mechanisms may be related to cognitive loss, such as cerebral hypoperfusion, atrophy and loss of gray matter of the brain, and dysfunction of the autonomic nervous system. The literature is clear regarding the benefits of aerobic physical activity in healthy populations in the modulation of the autonomic nervous system and in brain functions. Studies have shown that in the population of patients with heart failure, exercise is associated with an improvement in cognitive function, as well as in cardiac autonomic regulation. However, little emphasis has been given to the mechanisms by which aerobic physical activity can benefit brain functioning, the autonomic nervous system and result in better cognitive performance, particularly in patients with heart failure. Therefore, the present work presents the ways in which brain areas responsible for cognition also act in the modulation of the autonomic nervous system, and emphasizes its importance for the understanding of cognitive impairment in relation to the pathophysiology of heart failure. It is also described the way in which aerobic physical activity can promote benefits when it is integrated into the therapy, associated to a better prognosis of the clinical picture of these patients.
Amanda Lucas da Costa
Full Text Available Abstract To evaluate the relationship of obesity, cognitive impairment and depressive symptoms in patients with high cardiovascular risk. Methods: A sample of 93 patients aged 50 years or older was selected from the Center of Dyslipidemia and High Cardiovascular Risk from Hospital de Clínicas de Porto Alegre (HCPA. Patients with stroke were excluded. For cognitive evaluation, the MMSE (Mini Mental State Examination was used. A score of 24 or less was considered as cognitive impairment, and for those who had 4 years or less of education, the cutoff point was 17. The GDS-15 (Geriatric Depression Scale was also used, with the cutoff of 6 for presence of depressive symptoms. Results: Obese patients showed lower mean MMSE scores compared to non-obese patients (p=0.0012. Additionally, for every one point increase in BMI above 30 there was a 27% increase in the chances of the patient having cognitive impairment. The obese patients presented 31% chance of having cognitive impairment compared with overweight subjects. Conclusions: Our findings corroborated the association between obesity and cognitive impairment in high cardiovascular risk patients. This association however, was not observed for depressive symptoms.
Heser, Kathrin; Bleckwenn, Markus; Wiese, Birgitt; Mamone, Silke; Riedel-Heller, Steffi G; Stein, Janine; Lühmann, Dagmar; Posselt, Tina; Fuchs, Angela; Pentzek, Michael; Weyerer, Siegfried; Werle, Jochen; Weeg, Dagmar; Bickel, Horst; Brettschneider, Christian; König, Hans-Helmut; Maier, Wolfgang; Scherer, Martin; Wagner, Michael
Late-life depression is frequently accompanied by cognitive impairments. Whether these impairments indicate a prodromal state of dementia, or are a symptomatic expression of depression per se is not well-studied. In a cohort of very old initially non-demented primary care patients (n = 2,709, mean age = 81.1 y), cognitive performance was compared between groups of participants with or without elevated depressive symptoms and with or without subsequent dementia using ANCOVA (adjusted for age, sex, and education). Logistic regression analyses were computed to predict subsequent dementia over up to six years of follow-up. The same analytical approach was performed for lifetime major depression. Participants with elevated depressive symptoms without subsequent dementia showed only small to medium cognitive deficits. In contrast, participants with depressive symptoms with subsequent dementia showed medium to very large cognitive deficits. In adjusted logistic regression models, learning and memory deficits predicted the risk for subsequent dementia in participants with depressive symptoms. Participants with a lifetime history of major depression without subsequent dementia showed no cognitive deficits. However, in adjusted logistic regression models, learning and orientation deficits predicted the risk for subsequent dementia also in participants with lifetime major depression. Marked cognitive impairments in old age depression should not be dismissed as "depressive pseudodementia", but require clinical attention as a possible sign of incipient dementia. Non-depressed elderly with a lifetime history of major depression, who remained free of dementia during follow-up, had largely normal cognitive performance.
Beeckmans, Kurt; Crunelle, Cleo; Van Ingelgom, Silke; Michiels, Karla; Dierckx, Eva; Vancoillie, Patrick; Hauman, Henri; Sabbe, Bernard
In this study, we evaluated persistent cognitive deficits in whiplash injury (WI) patients and compared these to cognitive functioning in mild traumatic brain injury (MTBI) patients and healthy controls (HC). Sixty-one patients suffering from a WI were compared with 57 patients suffering from a MTBI and with 30 HC. They were examined with an extensive neuropsychological test battery assessing attention, memory, and visuospatial and executive functions. In both patient groups, participants showed persistent cognitive symptoms (more than 6 months post-injury). The two patient groups did not differ significantly with regard to measurements of attention, memory, and visuospatial and executive functions. The WI group, as compared to the HC group, was found to be significantly more deficient in speed of performance during sustained and divided attention, focused attention, alternating attention, the storage of new auditory-verbal unrelated information into memory, the long-term delayed recall of stored auditory-verbal related information from memory, abstract reasoning and accuracy of performance during planning and problem solving. No differences could be found between both groups concerning speed of information processing, visuospatial abilities and verbal fluency.
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. © 2016 The British Psychological Society.
Zetsche, Ulrike; Rief, Winfried; Westermann, Stefan; Exner, Cornelia
The present study examines the interplay between cognitive deficits and emotional context in obsessive-compulsive disorder (OCD) and social phobia (SP). Specifically, this study examines whether the inflexible use of efficient learning strategies in an emotional context underlies impairments in probabilistic classification learning (PCL) in OCD, and whether PCL impairments are specific to OCD. Twenty-three participants with OCD, 30 participants with SP and 30 healthy controls completed a neutral and an OCD-specific PCL task. OCD participants failed to adopt efficient learning strategies and showed fewer beneficial strategy switches than controls only in an OCD-specific context, but not in a neutral context. Additionally, OCD participants did not show any explicit memory impairments. Number of beneficial strategy switches in the OCD-specific task mediated the difference in PCL performance between OCD and control participants. Individuals with SP were impaired in both PCL tasks. In contrast to neuropsychological models postulating general cognitive impairments in OCD, the present findings suggest that it is the interaction between cognition and emotion that is impaired in OCD. Specifically, activated disorder-specific fears may impair the flexible adoption of efficient learning strategies and compromise otherwise unimpaired PCL. Impairments in PCL are not specific to OCD.
Lindner, M D; Plone, M A; Schallert, T; Emerich, D F
The Morris water maze is commonly used to test cognitive function in rodent models of neurological disorders including age-related cognitive deficits. It is often assumed that the most profoundly impaired aged rats may be blind due to retinal degeneration, and it has been reported that animals with visual sensory deficits can be identified based on their performance in a cued platform task. The results of the present study demonstrate that blind rats can perform surprisingly well in the reference memory version of the Morris water maze, and that blind rats cannot be selectively excluded based on performance in the cued platform task since atropine-treated rats also perform poorly in the cued platform task. Future studies may be able to develop screening procedures that help to eliminate subjects with non-cognitive deficits, but the present results do not support the use of the cued platform or straight swim task as screening procedures. Experimenters must be careful to consider the role that visual sensory function and other non-cognitive factors may have in performance of the spatial learning Morris water maze, and also the role that severe cognitive deficits may have in performance of the cued platform task.
Fritz, Nora E; Hamana, Katy; Kelson, Mark; Rosser, Anne; Busse, Monica; Quinn, Lori
Huntington disease (HD) results in a range of cognitive and motor impairments that progress throughout the disease stages; however, little research has evaluated specific dual-task abilities in this population, and the degree to which they may be related to functional ability. The purpose of this study was to a) examine simple and complex motor-cognitive dual-task performance in individuals with HD, b) determine relationships between dual-task walking ability and disease-specific measures of motor, cognitive and functional ability, and c) examine the relationship of dual-task measures to falls in individuals with HD. Thirty-two individuals with HD were evaluated for simple and complex dual-task ability using the Walking While Talking Test. Demographics and disease-specific measures of motor, cognitive and functional ability were also obtained. Individuals with HD had impairments in simple and complex dual-task ability. Simple dual-task walking was correlated to disease-specific motor scores as well as cognitive performance, but complex dual-task walking was correlated with total functional capacity, as well as a range of cognitive measures. Number of prospective falls was moderately-strongly correlated to dual-task measures. Our results suggest that individuals with HD have impairments in cognitive-motor dual-task ability that are related to disease progression and specifically functional ability. Dual-task measures appear to evaluate a unique construct in individuals with early to mid-stage HD, and may have value in improving the prediction of falls risk in this population. Copyright © 2016 Elsevier B.V. All rights reserved.
Pellicano, E.; Maybery, M.; Durkin, K.; Maley, A.
This study examined the validity of “weak” central coherence (CC) in the context of multiple cognitive capabilities/deficits in autism. Children with an autism spectrum disorder (ASD) and matched typically developing children were administered tasks tapping visuospatial coherence, false-belief understanding and aspects of executive control. Significant group differences were found in all three cognitive domains. Evidence of local processing on coherence tasks was widespread in the ASD group, ...
Full Text Available Background: Speech disorders already occur in the early phases of Alzheimer's disease (AD. As a possible cause, problems of executive processes are discussed. Cognitive slowing is also repeatedly addressed. Aims: Are there any connections between cognitive slowing and speech disorders in AD? And is there a relationship between cognitive slowing and executive processes? Methods: The data of 72 healthy controls and 52 AD patients were examined with regard to their language performance and their response times in a computerized Stroop paradigm. Results: The AD patients showed significantly worse results in all language tests as well as much longer reaction times in all Stroop conditions, especially in the interference condition (Stroop 3. Speech errors and response times correlated with severity (MMSE, and the speech errors correlated with the reaction times in Stroop 3 (interference condition, which reflects the processing time of executive processes. Conclusion: The most interesting question now is: How are language processing and executive processing time (Stroop 3 related?
Hinshaw, Stephen P
This study investigated a diverse sample of girls (6-12 years of age) with attention-deficit/hyperactivity disorder (ADHD), combined type (n = 93) and inattentive type (n = 47), plus age- and ethnicity-matched comparison girls (n = 88), who participated in research summer programs. Speech and language problems, grade retention, and adoption characterized the ADHD sample; documented abuse characterized the combined type. Girls with ADHD showed dysfunction in terms of externalizing and internalizing behaviors and comorbidities, cognitive and academic performance, authoritarian parenting, and peer status. The inattentive type was more socially isolated but less rejected by peers than the combined type. ADHD-related impairment was independent of age and disruptive comorbidity. Further examination of processes related to psychopathology and competencies in girls with ADHD is needed.
Garner, Annie A.; Peugh, James; Becker, Stephen P.; Kingery, Kathleen M.; Tamm, Leanne; Vaughn, Aaron J.; Ciesielski, Heather; Simon, John O.; Loren, Richard E. A.; Epstein, Jeffery N.
Objective Studies demonstrate sluggish cognitive tempo (SCT) symptoms to be distinct from inattentive and hyperactive-impulsive dimensions of Attention-Deficit/Hyperactivity Disorder (ADHD). No study has examined SCT within a bi-factor model of ADHD whereby SCT may form a specific factor distinct from inattention and hyperactivity/impulsivity while still fitting within a general ADHD factor, which was the purpose of the current study. Method 168 children were recruited from an ADHD clinic. Most (92%) met diagnostic criteria for ADHD. Parents and teachers completed measures of ADHD and SCT. Results Although SCT symptoms were strongly associated with inattention they loaded onto a factor independent of ADHD ‘g’. Results were consistent across parent and teacher ratings. Conclusions SCT is structurally distinct from inattention as well as from the general ADHD latent symptom structure. Findings support a growing body of research suggesting SCT to be distinct and separate from ADHD. PMID:25005039
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
Billard, C; Fluss, J; Ducot, B; Bricout, L; Richard, G; Ecalle, J; Magnan, A; Warszawski, J; Ziegler, J
Reading impairment is the major learning disability in children. While research on illiteracy has mainly been conducted from a sociological perspective, research on dyslexia has typically been studied from a cognitive-linguistic perspective. Studies that jointly investigate sociological, behavioral and cognitive factors in predicting reading outcome are rare and limited to English-speaking populations. The goal of the present study was to screen second grade children with reading impairment in French urban elementary schools and to pin down the factors that explain the various facets of reading failure and success. A total of 1062 children from 20 different schools in the city of Paris participated in the study. Different aspects of reading were assessed individually for children with a suspected impairment in reading acquisition. Subsequently, 131 poor readers and 50 typically developing readers were matched for sex, age, and school. For these children, medical, cognitive, behavioral and individual socioeconomic data were obtained. Group differences were examined and multiple regression analyses were conducted to examine how much variance in reading was explained by the various variables. The prevalence of poor reading skills in grade 2 was highly influenced by neighborhood socioeconomic status (SES) (ranging from 3.3% in high SES to 20.5% in low SES areas). Among the SES variables, employment of the father was a significant predictor of poor reading. Among the cognitive variables, phonological awareness and rapid naming were the most significant factors, much more than verbal or nonverbal intelligence. Among the behavioral variables, attention was an important factor but not externalized symptoms. Multiple regression analyses showed that reading outcome was best predicted by phonological awareness skills and attention deficits. The majority of children with reading disability come from low SES areas. As in the English literature, the most robust predictor for
Giralt, Albert; Brito, Veronica; Chevy, Quentin; Simonnet, Clé mence; Otsu, Yo; Cifuentes-Dí az, Carmen; Pins, Benoit de; Coura, Renata; Alberch, Jordi; Giné s, Sí lvia; Poncer, Jean-Christophe; Girault, Jean-Antoine
The structure and function of spines and excitatory synapses are under the dynamic control of multiple signalling networks. Although tyrosine phosphorylation is involved, its regulation and importance are not well understood. Here we study the role of Pyk2, a non-receptor calcium-dependent protein-tyrosine kinase highly expressed in the hippocampus. Hippocampal-related learning and CA1 long-term potentiation are severely impaired in Pyk2-deficient mice and are associated with alterations in NMDA receptors, PSD-95 and dendritic spines. In cultured hippocampal neurons, Pyk2 has autophosphorylation-dependent and -independent roles in determining PSD-95 enrichment and spines density. Pyk2 levels are decreased in the hippocampus of individuals with Huntington and in the R6/1 mouse model of the disease. Normalizing Pyk2 levels in the hippocampus of R6/1 mice rescues memory deficits, spines pathology and PSD-95 localization. Our results reveal a role for Pyk2 in spine structure and synaptic function, and suggest that its deficit contributes to Huntington’s disease cognitive impairments.
Waber, Deborah P; Bryce, Cyralene P; Girard, Jonathan M; Fischer, Laura K; Fitzmaurice, Garrett M; Galler, Janina R
We compared the IQ and academic achievement of the young adult offspring of parents malnourished in infancy and those of a healthy control group in order to test the hypothesis that the offspring of previously malnourished individuals would show IQ and academic deficits that could be related to reduced parental socioeconomic status. We conducted a group comparison study based on a community sample in Barbados (Barbados Nutrition Study). Participants were adult children ≥16 years of age whose parents had been malnourished during the first year of life (n = 64; Mean age 19.3 years; 42% male) or whose parents were healthy community controls (n = 50; Mean age 19.7 years; 48% male). The primary outcome was estimated IQ (Wechsler Abbreviated Scale of Intelligence); a secondary outcome was academic achievement (Wide Range Achievement Test - Third Edition). Data were analyzed using PROC MIXED with and without adjusting for parental socioeconomic status (Hollingshead Index of Social Position). IQ was reduced in the offspring of previously malnourished parents relative to the offspring of controls (9.8 point deficit; P malnutrition on cognitive function may be transmitted to the next generation; however, this intergenerational effect does not appear to be explained by the reduced socioeconomic status or IQ of the parent generation.
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. © The Author(s) 2014.
The structure and function of spines and excitatory synapses are under the dynamic control of multiple signalling networks. Although tyrosine phosphorylation is involved, its regulation and importance are not well understood. Here we study the role of Pyk2, a non-receptor calcium-dependent protein-tyrosine kinase highly expressed in the hippocampus. Hippocampal-related learning and CA1 long-term potentiation are severely impaired in Pyk2-deficient mice and are associated with alterations in NMDA receptors, PSD-95 and dendritic spines. In cultured hippocampal neurons, Pyk2 has autophosphorylation-dependent and -independent roles in determining PSD-95 enrichment and spines density. Pyk2 levels are decreased in the hippocampus of individuals with Huntington and in the R6/1 mouse model of the disease. Normalizing Pyk2 levels in the hippocampus of R6/1 mice rescues memory deficits, spines pathology and PSD-95 localization. Our results reveal a role for Pyk2 in spine structure and synaptic function, and suggest that its deficit contributes to Huntington’s disease cognitive impairments.
McLean, Samantha L; Harte, Michael K; Neill, Joanna C; Young, Andrew Mj
Dopamine dysregulation in the prefrontal cortex (PFC) plays an important role in cognitive dysfunction in schizophrenia. Sub-chronic phencyclidine (scPCP) treatment produces cognitive impairments in rodents and is a thoroughly validated animal model for cognitive deficits in schizophrenia. The aim of our study was to investigate the role of PFC dopamine in scPCP-induced deficits in a cognitive task of relevance to the disorder, novel object recognition (NOR). Twelve adult female Lister Hooded rats received scPCP (2 mg/kg) or vehicle via the intraperitoneal route twice daily for 7 days, followed by 7 days washout. In vivo microdialysis was carried out prior to, during and following the NOR task. Vehicle rats successfully discriminated between novel and familiar objects and this was accompanied by a significant increase in dopamine in the PFC during the retention trial ( p dopamine increase was observed. These data demonstrate an increase in dopamine during the retention trial in vehicle rats that was not observed in scPCP-treated rats accompanied by cognitive disruption in the scPCP group. This novel finding suggests a mechanism by which cognitive deficits are produced in this animal model and support its use for investigating disorders in which PFC dopamine is central to the pathophysiology.
Yu, Yu-Wen; Hsieh, Tsung-Hsun; Chen, Kai-Yun; Wu, John Chung-Che; Hoffer, Barry J.; Greig, Nigel H.; Li, Yazhou; Lai, Jing-Huei; Chang, Cheng-Fu; Lin, Jia-Wei; Chen, Yu-Hsin
Abstract Mild traumatic brain injury (mTBI) is a major public health issue, representing 75–90% of all cases of TBI. In clinical settings, mTBI, which is defined as a Glascow Coma Scale (GCS) score of 13–15, can lead to various physical, cognitive, emotional, and psychological-related symptoms. To date, there are no pharmaceutical-based therapies to manage the development of the pathological deficits associated with mTBI. In this study, the neurotrophic and neuroprotective properties of glucose-dependent insulinotropic polypeptide (GIP), an incretin similar to glucagon-like peptide-1 (GLP-1), was investigated after its steady-state subcutaneous administration, focusing on behavior after mTBI in an in vivo animal model. The mTBI rat model was generated by a mild controlled cortical impact (mCCI) and used to evaluate the therapeutic potential of GIP. We used the Morris water maze and novel object recognition tests, which are tasks for spatial and recognition memory, respectively, to identify the putative therapeutic effects of GIP on cognitive function. Further, beam walking and the adhesive removal tests were used to evaluate locomotor activity and somatosensory functions in rats with and without GIP administration after mCCI lesion. Lastly, we used immunohistochemical (IHC) staining and Western blot analyses to evaluate the inflammatory markers, glial fibrillary acidic protein (GFAP), amyloid-β precursor protein (APP), and bone marrow tyrosine kinase gene in chromosome X (BMX) in animals with mTBI. GIP was well tolerated and ameliorated mTBI-induced memory impairments, poor balance, and sensorimotor deficits after initiation in the post-injury period. In addition, GIP mitigated mTBI-induced neuroinflammatory changes on GFAP, APP, and BMX protein levels. These findings suggest GIP has significant benefits in managing mTBI-related symptoms and represents a novel strategy for mTBI treatment. PMID:26972789
Full Text Available Myotonic dystrophy type-1 (DM1 is a genetic multi-systemic disorder involving several organs including the brain. Despite the heterogeneity of this condition, some patients with non-congenital DM1 can present with minimal cognitive impairment on formal testing but with severe difficulties in daily-living activities including social interactions. One explanation for this paradoxical mismatch can be found in patients' dysfunctional social cognition, which can be assessed in the framework of the Theory of Mind (ToM. We hypothesize here that specific disease driven abnormalities in DM1 brains may result in ToM impairments. We recruited 20 DM1 patients who underwent the "Reading the Mind in the Eyes" and the ToM-story tests. These patients, together with 18 healthy controls, also underwent resting-state functional MRI. A composite Theory of Mind score was computed for all recruited patients and correlated with their brain functional connectivity. This analysis provided the patients' "Theory of Mind-network", which was compared, for its topological properties, with that of healthy controls. We found that DM1 patients showed deficits in both tests assessing ToM. These deficits were associated with specific patterns of abnormal connectivity between the left inferior temporal and fronto-cerebellar nodes in DM1 brains. The results confirm the previous suggestions of ToM dysfunctions in patients with DM1 and support the hypothesis that difficulties in social interactions and personal relationships are a direct consequence of brain abnormalities, and not a reaction symptom. This is relevant not only for a better pathophysiological comprehension of DM1, but also for non-pharmacological interventions to improve clinical aspects and impact on patients' success in life.
Kim, Se Hee; Han, Doug Hyun; Lee, Young Sik; Kim, Bung-Nyun; Cheong, Jae Hoon; Han, Sang Ho
Attention deficit hyperactivity disorder (ADHD) symptoms are associated with the deficit in executive functions. Playing Go involves many aspect of cognitive function and we hypothesized that it would be effective for children with ADHD. Seventeen drug naïve children with ADHD and seventeen age and sex matched comparison subjects were participated. Participants played Go under the instructor's education for 2 hours/day, 5 days/week. Before and at the end of Go period, clinical symptoms, cognitive functions, and brain EEG were assessed with Dupaul's ADHD scale (ARS), Child depression inventory (CDI), digit span, the Children's Color Trails Test (CCTT), and 8-channel QEEG system (LXE3208, Laxtha Inc., Daejeon, Korea). There were significant improvements of ARS total score (z=2.93, p<0.01) and inattentive score (z=2.94, p<0.01) in children with ADHD. However, there was no significant change in hyperactivity score (z=1.33, p=0.18). There were improvement of digit total score (z=2.60, p<0.01; z=2.06, p=0.03), digit forward score (z=2.21, p=0.02; z=2.02, p=0.04) in both ADHD and healthy comparisons. In addition, ADHD children showed decreased time of CCTT-2 (z=2.21, p=0.03). The change of theta/beta right of prefrontal cortex during 16 weeks was greater in children with ADHD than in healthy comparisons (F=4.45, p=0.04). The change of right theta/beta in prefrontal cortex has a positive correlation with ARS-inattention score in children with ADHD (r=0.44, p=0.03). We suggest that playing Go would be effective for children with ADHD by activating hypoarousal prefrontal function and enhancing executive function.
Conclusions: VCmax and ACmax are governed mainly by the action of the Parasympathetic Nervous System, through acetylcholine. The results of this study demonstrate that the CNS may be affected in MG and support the hypothesis that MG has central cholinergic effects manifested by cognitive dysfunction.
Takeda, Kazuyoshi; Sumiyoshi, Tomiki; Matsumoto, Madoka; Murayama, Kou; Ikezawa, Satoru; Matsumoto, Kenji; Nakagome, Kazuyuki
The ultimate goal of the treatment of schizophrenia is recovery, a notion related to improvement of cognitive and social functioning. Cognitive remediation therapies (CRT), one of the most effective cognition enhancing methods, have been shown to moderately improve social functioning. For this purpose, intrinsic motivation, related to internal values such as interest and enjoyment, has been shown to play a key role. Although the impairment of intrinsic motivation is one of the characteristics of schizophrenia, its neural mechanisms remain unclear. This is related to the lack of feasible measures of intrinsic motivation, and its response to treatment. According to the self-determination theory (SDT), not only intrinsic motivation, but extrinsic motivation has been reported to enhance learning and memory in healthy subjects to some extent. This finding suggests the contribution of different types of motivation to potentiate the ability of the CRT to treat cognitive impairment of schizophrenia. In this paper, we provide a review of psychological characteristics, assessment methods, and neural correlates of intrinsic motivation in healthy subjects and patients with schizophrenia. Particularly, we focus on neuroimaging studies of intrinsic motivation, including our own. These considerations are relevant to enhancement of functional outcomes of schizophrenia. PMID:29922185
Preiss, M.; Kučerová, H.; Štěpánková, H.; Sos, P.; Lukavský, Jiří; Kawaciuková, R.
Roč. 11, Suppl. 3 (2007), s. 79-83 ISSN 1211-7579 Institutional research plan: CEZ:AV0Z70250504 Keywords : major depressive episode * remission * cognitive function Subject RIV: AN - Psychology http://www.tigis.cz/PSYCHIAT/Psych_suppl_3_07/21Preiss_suppl_3_07.pdf)
Full Text Available The ultimate goal of the treatment of schizophrenia is recovery, a notion related to improvement of cognitive and social functioning. Cognitive remediation therapies (CRT, one of the most effective cognition enhancing methods, have been shown to moderately improve social functioning. For this purpose, intrinsic motivation, related to internal values such as interest and enjoyment, has been shown to play a key role. Although the impairment of intrinsic motivation is one of the characteristics of schizophrenia, its neural mechanisms remain unclear. This is related to the lack of feasible measures of intrinsic motivation, and its response to treatment. According to the self-determination theory (SDT, not only intrinsic motivation, but extrinsic motivation has been reported to enhance learning and memory in healthy subjects to some extent. This finding suggests the contribution of different types of motivation to potentiate the ability of the CRT to treat cognitive impairment of schizophrenia. In this paper, we provide a review of psychological characteristics, assessment methods, and neural correlates of intrinsic motivation in healthy subjects and patients with schizophrenia. Particularly, we focus on neuroimaging studies of intrinsic motivation, including our own. These considerations are relevant to enhancement of functional outcomes of schizophrenia.
Small, Brent J; Rawson, Kerri Sharp; Walsh, Erin; Jim, Heather S L; Hughes, Tiffany F; Iser, Lindsay; Andrykowski, Michael A; Jacobsen, Paul B
Recent attention has focused on the negative effects of chemotherapy on the cognitive performance of cancer survivors. The current study examined modification of this risk by catechol-O-methyltransferase (COMT) genotype based on evidence in adult populations that the presence of a Val allele is associated with poorer cognitive performance. Breast cancer survivors treated with radiotherapy (n = 58), and/or chemotherapy (n = 72), and 204 healthy controls (HCs) completed tests of cognitive performance and provided saliva for COMT genotyping. COMT genotype was divided into Val carriers (Val+; Val/Val, Val/Met) or COMT-Met homozygote carriers (Met; Met/Met). COMT-Val+ carriers performed more poorly on tests of attention, verbal fluency, and motor speed relative to COMT-Met homozygotes. Moreover, COMT-Val+ carriers treated with chemotherapy performed more poorly on tests of attention relative to HC group members who were also Val+ carriers. The results suggest that persons treated with chemotherapy for breast cancer who also possess the COMT-Val gene are susceptible to negative effects on their cognitive health. This research is important because it strives to understand the factors that predispose some cancer survivors to more negative quality-of-life outcomes. Copyright © 2010 American Cancer Society.
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…
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. (c) 2007 Wiley Periodicals, Inc.
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...
Dorofeikova, Mariia; Neznanov, Nikolay; Petrova, Nataliia
The aim of this study was to search for correlates of cognitive impairment in patients with paranoid schizophrenia among clinical, demographic, anamnestic and biochemical markers (NSE, S100B protein, BDNF, hs-CRP). Patients with paranoid schizophrenia (n=125) were examined using the Brief Assessment of Cognitive Function in Schizophrenia, the Rey-Osterrieth Complex Figure task, and a number of clinical scales including the Positive and Negative Syndrome Scale. The majority of patients demonstrated cognitive impairment. The type of impairment was highly heterogeneous and individual. Relationships were found between the degree of executive functioning and family history of mental illness; working memory and age of onset of schizophrenia; and visual memory and psychopathological symptomatology. Negative and affective symptoms were not significantly associated with cognitive functioning. Treatment with first generation antipsychotics was associated with a more frequent impairment of motor skills, and concomitant anticholinergic drugs, with reduced accuracy. Use of second-generation antipsychotics only was associated with better accuracy, working memory and speech fluency. Among the patients, 21.4% had signs of a systemic inflammatory response, indicating a possible role of inflammatory response in the development of schizophrenia. CRP, S100B and NSE levels reflected features of the course of illness and therapeutic response. Patients with lower concentrations of BDNF were characterized by lower processing speeds. Copyright © 2017 Elsevier B.V. All rights reserved.
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…
Sun, Jie; Cai, Rongrong; Huang, Rong; Wang, Pin; Tian, Sai; Sun, Haixia; Xia, Wenqing; Wang, Shaohua
Cholesteryl ester transfer protein (CETP) is involved in diabetic dyslipidemia. We aim to test the hypothesis that CETP might be of importance in mediating dyslipidemia-related susceptibility to cognitive deficits in diabetic patients. We recruited 190 type 2 diabetic patients and divided them into two groups according to the Montreal Cognitive Assessment (MoCA) score. The association between CETP and cognitive decline was analyzed with logistic regression and stratification. There were 110 diabetic patients with mild cognition impairment (MCI) and 80 healthy cognition subjects as controls. Dyslipidemia is more common among diabetic patients with MCI; they had a significant increase of serum CETP concentrations, which was negatively correlated with MoCA (r = -0.638; p dyslipidemia-related susceptibility to cognitive decline, especially memory function in type 2 diabetic patients.
Jiao, Shu-Sheng; Yao, Xiu-Qing; Liu, Yu-Hui; Wang, Qing-Hua; Zeng, Fan; Lu, Jian-Jun; Liu, Jia; Zhu, Chi; Shen, Lin-Lin; Liu, Cheng-Hui; Wang, Ye-Ran; Zeng, Gui-Hua; Parikh, Ankit; Chen, Jia; Liang, Chun-Rong; Xiang, Yang; Bu, Xian-Le; Deng, Juan; Li, Jing; Xu, Juan; Zeng, Yue-Qin; Xu, Xiang; Xu, Hai-Wei; Zhong, Jin-Hua; Zhou, Hua-Dong; Zhou, Xin-Fu; Wang, Yan-Jiang
Alzheimer’s disease (AD) is one of most devastating diseases affecting elderly people. Amyloid-β (Aβ) accumulation and the downstream pathological events such as oxidative stress play critical roles in pathogenesis of AD. Lessons from failures of current clinical trials suggest that targeting multiple key pathways of the AD pathogenesis is necessary to halt the disease progression. Here we show that Edaravone, a free radical scavenger that is marketed for acute ischemic stroke, has a potent capacity of inhibiting Aβ aggregation and attenuating Aβ-induced oxidation in vitro. When given before or after the onset of Aβ deposition via i.p. injection, Edaravone substantially reduces Aβ deposition, alleviates oxidative stress, attenuates the downstream pathologies including Tau hyperphosphorylation, glial activation, neuroinflammation, neuronal loss, synaptic dysfunction, and rescues the behavioral deficits of APPswe/PS1 mice. Oral administration of Edaravone also ameliorates the AD-like pathologies and memory deficits of the mice. These findings suggest that Edaravone holds a promise as a therapeutic agent for AD by targeting multiple key pathways of the disease pathogenesis. PMID:25847999
von Rhein, Daniel; Mennes, Maarten; van Ewijk, Hanneke; Groenman, Annabeth P.; Zwiers, Marcel P.; Oosterlaan, Jaap; Heslenfeld, Dirk; Franke, Barbara; Hoekstra, Pieter J.; Faraone, Stephen V.; Hartman, Catharina; Buitelaar, Jan
Attention-deficit/hyperactivity disorder (ADHD) is a persistent neuropsychiatric disorder which is associated with impairments on a variety of cognitive measures and abnormalities in structural and functional brain measures. Genetic factors are thought to play an important role in the etiology of
von Rhein, D; Mennes, M.; van Ewijk, H.; Groenman, A.P.; Zwiers, M.P.; Oosterlaan, J.; Heslenfeld, D.J.; Franke, B.; Hoekstra, P.J.; Faraone, S.V.; Hartman, C.A.; Buitelaar, J.K.
Attention-deficit/hyperactivity disorder (ADHD) is a persistent neuropsychiatric disorder which is associated with impairments on a variety of cognitive measures and abnormalities in structural and functional brain measures. Genetic factors are thought to play an important role in the etiology of
Rhein, D.T. von; Mennes, M.; Ewijk, H. van; Groenman, A.P.; Zwiers, M.P.; Oosterlaan, J.; Heslenfeld, D.; Franke, B.; Hoekstra, P.J.; Faraone, S.V; Hartman, C.; Buitelaar, J.K.
Attention-deficit/hyperactivity disorder (ADHD) is a persistent neuropsychiatric disorder which is associated with impairments on a variety of cognitive measures and abnormalities in structural and functional brain measures. Genetic factors are thought to play an important role in the etiology of
Hagberg, Bibbi S.; Miniscalco, Carmela; Gillberg, Christopher
Many studies have shown that children with autism spectrum disorders (ASD) and attention-deficit/hyperactivity disorder (ADHD) have had early indicators of language delay. The aim of the present study was to examine the cognitive profile of school age children referred to a specialist clinic for ASD, ADHD, or both, and relate this profile…
Jonsdottir, S; Bouma, A; Sergeant, JA; Scherder, EJA; Bouma, J.M.
Objective. The aim of this study was to examine the effects of transcutaneous electrical nerve stimulation (TENS) on cognition, behavior, and the rest-activity rhythm in children with attention deficit hyperactivity disorder, combined type (ADHD-CT). Methods. Twenty-two children diagnosed with
Jonsdottir, S.; Bouma, A.; Sergeant, J.A.; Scherder, E.J.A.
Objective. The aim of this study was to examine the effects of transcutaneous electrical nerve stimulation (TENS) on cognition, behavior, and the rest-activity rhythm in children with attention deficit hyperactivity disorder, combined type (ADHD-CT). Methods. Twenty-two children diagnosed with
Riggs, Paula D.; Winhusen, Theresa; Davies, Robert D.; Leimberger, Jeffrey D.; Mikulich-Gilbertson, Susan; Klein, Constance; Macdonald, Marilyn; Lohman, Michelle; Bailey, Genie L.; Haynes, Louise; Jaffee, William B.; Haminton, Nancy; Hodgkins, Candace; Whitmore, Elizabeth; Trello-Rishel, Kathlene; Tamm, Leanne; Acosta, Michelle C.; Royer-Malvestuto, Charlotte; Subramaniam, Geetha; Fishman, Marc; Holmes, Beverly W.; Kaye, Mary Elyse; Vargo, Mark A.; Woody, George E.; Nunes, Edward V.; Liu, David
Objective: To evaluate the efficacy and safety of osmotic-release methylphenidate (OROS-MPH) compared with placebo for attention-deficit/hyperactivity disorder (ADHD), and the impact on substance treatment outcomes in adolescents concurrently receiving cognitive-behavioral therapy (CBT) for substance use disorders (SUD). Method: This was a…
Zhou, Libin; Chen, Tingting; Li, Guoxi; Wu, Chaoming; Wang, Conghui; Li, Lin; Sha, Sha; Chen, Lei; Liu, George; Chen, Ling
A characteristic phenotype of congenital generalized lipodystrophy 2 (CGL2) that is caused by loss-of-function of seipin gene is mental retardation. Here, we show that seipin deficiency in hippocampal CA1 pyramidal cells caused the reduction of peroxisome proliferator-activated receptor gamma (PPARγ). Twelve-week-old systemic seipin knock-out mice and neuronal seipin knock-out (seipin-nKO) mice, but not adipose seipin knock-out mice, exhibited spatial cognitive deficits as assessed by the Morris water maze and Y-maze, which were ameliorated by the treatment with the PPARγ agonist rosiglitazone (rosi). In addition, seipin-nKO mice showed the synaptic dysfunction and the impairment of NMDA receptor-dependent LTP in hippocampal CA1 regions. The density of AMPA-induced current (IAMPA) in CA1 pyramidal cells and GluR1/GluR2 expression were significantly reduced in seipin-nKO mice, whereas the NMDA-induced current (INMDA) and NR1/NR2 expression were not altered. Rosi treatment in seipin-nKO mice could correct the decrease in expression and activity of AMPA receptor (AMPAR) and was accompanied by recovered synaptic function and LTP induction. Furthermore, hippocampal ERK2 and CREB phosphorylation in seipin-nKO mice were reduced and this could be rescued by rosi treatment. Rosi treatment in seipin-nKO mice elevated BDNF concentration. The MEK inhibitor U0126 blocked rosi-restored AMPAR expression and LTP induction in seipin-nKO mice, but the Trk family inhibitor K252a did not. These findings indicate that the neuronal seipin deficiency selectively suppresses AMPAR expression through reducing ERK-CREB activities, leading to the impairment of LTP and spatial memory, which can be rescued by PPARγ activation. Congenital generalized lipodystrophy 2 (CGL2), caused by loss-of-function mutation of seipin gene, is characterized by mental retardation. By the generation of systemic or neuronal seipin knock-out mice, the present study provides in vivo evidence that neuronal seipin
O'Malley, G K; McHugh, L; Mac Giollabhui, N; Bramham, J
To characterize adults with comorbid attention-deficit/hyperactivity-disorder (ADHD) and borderline personality disorder (BPD) with regard to ADHD symptoms, psychopathology, cognitive functioning and psychosocial factors. A between-group design compared a group of individuals diagnosed with ADHD (n=40) with a group diagnosed with BPD and who also met the criteria for ADHD (ADHD+BPD) (n=20). Significant differences were observed for both childhood and current impulsivity symptoms, whereby ADHD+BPD exhibited increased impulsivity; no differences on self-report and cognitive measures of impulsivity were reported. The ADHD+BPD group scored significantly higher on measures of depression, anxiety and numerous other axis I and II conditions. The ADHD+BPD group scored significantly lower on most measures of intellectual functioning and attention, however largely not on those relating to response inhibition. Furthermore, group differences were observed for psychosocial factors, including education, substance use and criminal record. Comorbid ADHD and BPD is characterized by more symptoms of impulsivity, additional psychopathology, comparatively lower intellectual and attentional functioning and increased psychosocial difficulties. Copyright © 2015. Published by Elsevier Masson SAS.
Zhang, Heng; Zhang, Ling; Zhou, Dongming; He, Xiao; Wang, Dongpi; Pan, Hongyu; Zhang, Xiaoqin; Mei, Yufei; Qian, Qi; Zheng, Tingting; Jones, Frank E; Sun, Binggui
Accumulation of amyloid β (Aβ) induces neuronal, synaptic, and cognitive deficits in patients and animal models of Alzheimer's disease (AD). The underlying mechanisms, however, remain to be fully elucidated. In the present study, we found that Aβ interacted with ErbB4, a member of the receptor tyrosine kinase family and mainly expressed in GABAergic interneurons. Deleting ErbB4 in parvalbumin-expressing neurons (PV neurons) significantly attenuated oligomeric Aβ-induced suppression of long term potentiation (LTP). Furthermore, specific ablation of ErbB4 in PV neurons via Cre/loxP system greatly improved spatial memory and synaptic plasticity in the hippocampus of hAPP-J20 mice. The deposition of Aβ detected by 3D6 and Thioflavin S staining and the proteolytic processing of hAPP analyzed by western blotting were not affected in the hippocampus of hAPP-J20 mice by deleting ErbB4 in PV neurons. Our data suggested that ErbB4 in PV neurons mediated Aβ-induced synaptic and cognitive dysfunctions without affecting Aβ levels. Copyright © 2017 Elsevier Inc. All rights reserved.
The decision to abolish British National Oil Corporation has greater significance than any commentator, so far, has cared to admit. Mr. Mabro says the Government has done much more than get rid of an institution it had previously weakened and emasculated; in effect, it had abdicated its responsibilities for the pricing of North Sea oil. He further observes that these moves may be consistent with the tenets of a simplistic free-market ideology: they betray, however, a lack of understanding of the economics of oil, and of the UK economic interest in oil.
Berg, John Erik
Electroconvulsive treatment (ECT) has developed over 70 years to a modern, effective way of lifting depressive moods. Memory loss and visual acuity after electroconvulsive treatment is the only remaining relevant criticism of the treatment modality when considering the overall rate of remission from this treatment compared to all other treatment modalities. A depressive state impedes memory, and memory improves on several qualities of cognition after treatment. However, the comparison of a pe...
Meier, Sandra L; Charleston, Alison J; Tippett, Lynette J
Amyotrophic lateral sclerosis, a progressive disease affecting motor neurons, may variably affect cognition and behaviour. We tested the hypothesis that functions associated with orbitomedial prefrontal cortex are affected by evaluating the behavioural and cognitive performance of 18 participants with amyotrophic lateral sclerosis without dementia and 18 healthy, matched controls. We measured Theory of Mind (Faux Pas Task), emotional prosody recognition (Aprosodia Battery), reversal of behaviour in response to changes in reward (Probabilistic Reversal Learning Task), decision making without risk (Holiday Apartment Task) and aberrant behaviour (Neuropsychiatric Inventory). We also assessed dorsolateral prefrontal function, using verbal and written fluency and planning (One-touch Stockings of Cambridge), to determine whether impairments in tasks sensitive to these two prefrontal regions co-occur. The patient group was significantly impaired at identifying social faux pas, recognizing emotions and decision-making, indicating mild, but consistent impairment on most measures sensitive to orbitomedial prefrontal cortex. Significant levels of aberrant behaviour were present in 50% of patients. Patients were also impaired on verbal fluency and planning. Individual subject analyses involved computing classical dissociations between tasks sensitive to different prefrontal regions. These revealed heterogeneous patterns of impaired and spared cognitive abilities: 33% of participants had classical dissociations involving orbitomedial prefrontal tasks, 17% had classical dissociations involving dorsolateral prefrontal tasks, 22% had classical dissociations between tasks of both regions, and 28% had no classical dissociations. These data indicate subtle changes in behaviour, emotional processing, decision-making and altered social awareness, associated with orbitomedial prefrontal cortex, may be present in a significant proportion of individuals with amyotrophic lateral sclerosis
McDonald, Skye; Rushby, Jacqueline A; Dalton, Katie I; Allen, Samantha K; Parks, Nicklas
The corpus callosum (CC) is vulnerable to severe traumatic brain injury (TBI). Social cognition requires integration of non-verbal and verbal information in order to understand social behaviour and may be compromised if the CC is damaged. 17 adults with severe, chronic TBI and 17 control participants underwent structural MRI and Diffusion Tensor Imaging. A region of interest analysis examined fractional anisotropy (FA) and mean diffusivity (MD) across regions of the CC. Performance on The Awareness of Social Inference Test (TASIT): part 1 (emotion recognition) and parts 2 and 3 (social inference), was examined in relation to FA and MD. Across participants, higher genu FA values were related to higher TASIT part 3 scores. Increased splenium FA was associated with better performance for TASIT parts 1-3. There was no association between DTI values and TASIT in the controls alone. In the TBI group, FA of the genu and splenium was correlated with TASIT part 3. The pattern of performance was similar when controlling for non-social cognitive ability. In conclusion, social information is complex and multi-modal requiring inter-hemispheric connection. People with TBI, regardless of focal grey matter injury, may lose social cognitive ability due to trauma related changes to the corpus callosum.
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
Pukhal'skiĭ, A L; Shmarina, G V; Aleshkin, V A
Long-term stress as well as physiological aging result in similar immunological and hormonal disturbances including hypothalamic-pituitary-adrenal) axis depletion, aberrant immune response (regulatory T-cells, Tregs, and T(h17)-lymphocyte accumulation) and decreased dehydroepian-drosterone synthesis both in the brain and in the adrenal glands. Since the main mechanisms of inflammation control, "prompt" (stress hormones) and "delayed" (Tregs), are broken, serum cytokine levels increase and become sufficient for blood-brain-barrier disruption. As a result peripheral cytokines penetrate into the brain where they begin to perform new functions. Structural and functional alterations of blood-brain-barrier as well as stress- (or age-) induced neuroinflammation promote influx of bone marrow derived dendritic cells and lymphocyte effectors into the brain parenchyma. Thereafter, mass intrusion ofpro-inflammatory mediators and immune cells having a lot of specific targets alters the brain work that we can observe both in humans and in animal experiments. The concept of stressful cognitive dysfunction, which is under consideration in this review, allows picking out several therapeutic targets: 1) reduction of excessive Treg accumulation; 2) supporting hypothalamic-pituitary-adrenal axis and inflammatory reaction attenuation; 3) recovery of dehydroepiandrosterone level; 4) improvement of blood-brain-barrier function.
Silverstein, Steven M
While cognitive impairment in schizophrenia is easy to demonstrate, it has been much more difficult to measure a specific cognitive process unconfounded by the influence of other cognitive processes and noncognitive factors (eg, sedation, low motivation) that affect test scores. With the recent interest in the identification of neurophysiology-linked cognitive probes for clinical trials, the issue of isolating specific cognitive processes has taken on increased importance. Recent advances in research design and psychometric theory regarding cognition research in schizophrenia demonstrate the importance of (1) maximizing between-group differences via reduction of measurement error during both test development and subsequent research and (2) the development and use of process-specific tasks in which theory-driven performance indices are derived across multiple conditions. Use of these 2 strategies can significantly advance both our understanding of schizophrenia and measurement sensitivity for clinical trials. Novel data-analytic strategies for analyzing change across multiple conditions and/or multiple time points also allow for increased reliability and greater measurement sensitivity than traditional strategies. Following discussion of these issues, trade-offs inherent to attempts to address psychometric issues in schizophrenia research are reviewed. Finally, additional considerations for maximizing sensitivity and real-world significance in clinical trials are discussed.
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
Huang, Fang; Sun, Li; Qian, Ying; Liu, Lu; Ma, Quan-Gang; Yang, Li; Cheng, Jia; Cao, Qing-Jiu; Su, Yi; Gao, Qian; Wu, Zhao-Min; Li, Hai-Mei; Qian, Qiu-Jin; Wang, Yu-Feng
Background: The cognitive function of children with either attention deficit hyperactivity disorder (ADHD) or learning disabilities (LDs) is known to be impaired. However, little is known about the cognitive function of children with comorbid ADHD and LD. The present study aimed to explore the cognitive function of children and adolescents with ADHD and learning difficulties in comparison with children with ADHD and healthy controls in different age groups in a large Chinese sample. Methods: Totally, 1043 participants with ADHD and learning difficulties (the ADHD + learning difficulties group), 870 with pure ADHD (the pure ADHD group), and 496 healthy controls were recruited. To investigate the difference in cognitive impairment using a developmental approach, all participants were divided into three age groups (6–8, 9–11, and 12–14 years old). Measurements were the Chinese-Wechsler Intelligence Scale for Children, the Stroop Color-Word Test, the Trail-Making Test, and the Behavior Rating Inventory of Executive Function-Parents (BRIEF). Multivariate analysis of variance was used. Results: The results showed that after controlling for the effect of ADHD symptoms, the ADHD + learning difficulties group was still significantly worse than the pure ADHD group, which was, in turn, worse than the control group on full intelligence quotient (98.66 ± 13.87 vs. 105.17 ± 14.36 vs. 112.93 ± 13.87, P ADHD symptoms, intelligence quotient, age, and gender. As for the age groups, the differences among groups became nonsignificant in the 12–14 years old group for inhibition (meaning interference of the Stroop Color-Word Test, 18.00 [13.00, 25.00] s vs. 17.00 [15.00, 26.00] s vs. 17.00 [10.50, 20.00] s, P = 0.704) and shift function (shifting time of the Trail-Making Test, 62.00 [43.00, 97.00] s vs. 53.00 [38.00, 81.00] s vs. 101.00 [88.00, 114.00] s, P = 0.778). Conclusions: Children and adolescents with ADHD and learning difficulties have more severe cognitive
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 - others: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
Vicari, Stefano; Piccini, Giorgia; Mercuri, Eugenio; Battini, Roberta; Chieffo, Daniela; Bulgheroni, Sara; Pecini, Chiara; Lucibello, Simona; Lenzi, Sara; Moriconi, Federica; Pane, Marika; D'Amico, Adele; Astrea, Guja; Baranello, Giovanni; Riva, Daria; Cioni, Giovanni; Alfieri, Paolo
This study aimed at comparing implicit sequence learning in individuals affected by Duchenne Muscular Dystrophy without intellectual disability and age-matched typically developing children. A modified version of the Serial Reaction Time task was administered to 32 Duchenne children and 37 controls of comparable chronological age. The Duchenne group showed a reduced rate of implicit learning even if in the absence of global intellectual disability. This finding provides further evidence of the involvement of specific aspects of cognitive function in Duchenne muscular dystrophy and on its possible neurobiological substrate.
Votruba, Kristen L; Persad, Carol; Giordani, Bruno
This study investigated whether healthy older adults with Mini-Mental State Examination (MMSE) scores above 23 exhibit cognitive impairment on neuropsychological tests. Participants completed the MMSE and a neuropsychological battery including tests of 10 domains. Results were compared to published normative data. On neuropsychological testing, participants performed well on measures of naming and recall but showed mild to moderate impairment in working memory and processing speed and marked impairment in inhibition, sustained attention, and executive functioning. Almost everyone (91%) scored at least 1 standard deviation (SD) below the mean in at least 1 domain. The median number of domains in which individuals scored below 1 SD was 3.0 of 10.0, whereas over 21% scored below 1 SD in 5 domains or more. With the strictest of definitions for impairment, 20% of this population scored below 2.0 SDs below the norm in at least 2 domains, a necessary condition for a diagnosis of dementia. The finding that cognitive impairment, particularly in attention and executive functioning, is found in healthy older persons who perform well on the MMSE has clinical and research implications in terms of emphasizing normal variability in performance and early identification of possible impairment. © The Author(s) 2016.
Full Text Available Background: Very few studies have evaluated the neurocognitive functions of patients with persistent delusional disorder. Aim: To study the neurocognitive profile of patients with delusional disorder and compare it with those of patients with paranoid schizophrenia and healthy control subjects. Materials and Methods: Attention concentration, executive functions, memory, and IQ were assessed in 20 patients with delusional disorder and were compared with 20 patients with paranoid schizophrenia and 20 healthy controls. All three groups were matched on age, sex, and level of education. The two patient groups were also matched on duration of illness. Results: In general, patients with delusional disorder performed worst than healthy controls and patients with paranoid schizophrenia performed in between the other two groups. Compared with healthy controls, both patients with delusional disorder and patients with paranoid schizophrenia were significantly impaired on different tests of attention and visual learning and memory. Compared with patients with paranoid schizophrenia, patients with delusional disorder had more impairment different tests of attention, visual learning and memory, verbal working memory, and executive functions. Conclusion: Patients with delusional disorder exhibit cognitive dysfunctions that are very similar to schizophrenia, but are more severe in intensity. The resemblance of cognitive profiles suggests that the two disorders may have similar etiological basis.
Redel, P; Bublak, P; Sorg, C; Kurz, A; Förstl, H; Müller, H J; Schneider, W X; Perneczky, R; Finke, K
Visual selective attention was assessed with a partial-report task in patients with probable Alzheimer's disease (AD), amnestic mild cognitive impairment (MCI), and healthy elderly controls. Based on Bundesen's "theory of visual attention" (TVA), two parameters were derived: top-down control of attentional selection, representing task-related attentional weighting for prioritizing relevant visual objects, and spatial distribution of attentional weights across the left and the right hemifield. Compared with controls, MCI patients showed significantly reduced top-down controlled selection, which was further deteriorated in AD subjects. Moreover, attentional weighting was significantly unbalanced across hemifields in MCI and tended to be more lateralized in AD. Across MCI and AD patients, carriers of the apolipoprotein E ε4 allele (ApoE4) displayed a leftward spatial bias, which was the more pronounced the younger the ApoE4-positive patients and the earlier disease onset. These results indicate that impaired top-down control may be linked to early dysfunction of fronto-parietal networks. An early temporo-parietal interhemispheric asymmetry might cause a pathological spatial bias which is associated with ApoE4 genotype and may therefore function as early cognitive marker of upcoming AD. Copyright © 2012 Elsevier Inc. All rights reserved.
Full Text Available The search for nootropic medications, which don't aggravate the implications of the hyperactivity disorder and sleep disturbances, is an urgent issue in the children's neurology. For the purpose of pantohamium sirupus appraisal, the researchers examined 20 patient aged between 3 years old and 4 years 11 months old, suffering from epilepsy with cognitive disorders and attention deficit and hyperactivity disorder. All the patients underwent interviewing with the composite questionnaire, oddball tasks, mechanical memory tests (memorizing 3–4 words, dynamic memory tests (repeating 2 groups of words, colour test (for the children of 4 years old, as well as electroencephalography and by indications clinical and biochemical examination. After the course of panto hamium sirupus treatment the researchers discovered the general improvement of attention, mechanical and dynamic memory, anxiety reduction and compensation boost based on the colour test conducted among the children, suffering from epilepsy with attention deficit and hyperactivity disorder. Most patients showed the improvement indices of the EEG background rhythm structure and normalization of background zone differences. The analysis of the obtained results allowed the researchers to conclude that pantohamium sirupus was safe and efficient in the complex therapy among the children, suffering from epilepsy with cognitive disorders and attention deficit and hyperactivity disorder.Key words: hopantenic acid, pantohamium, epilepsy, attention deficit, hyperactivity, cognitive disorders.
Ricobaraza, Ana; Cuadrado-Tejedor, Mar; Pérez-Mediavilla, Alberto; Frechilla, Diana; Del Río, Joaquin; García-Osta, Ana
Chromatin modification through histone acetylation is a molecular pathway involved in the regulation of transcription underlying memory storage. Sodium 4-phenylbutyrate (4-PBA) is a well-known histone deacetylase inhibitor, which increases gene transcription of a number of genes, and also exerts neuroprotective effects. In this study, we report that administration of 4-PBA reversed spatial learning and memory deficits in an established mouse model of Alzheimer's disease (AD) without altering beta-amyloid burden. We also observed that the phosphorylated form of tau was decreased in the AD mouse brain after 4-PBA treatment, an effect probably due to an increase in the inactive form of the glycogen synthase kinase 3beta (GSK3beta). Interestingly, we found a dramatic decrease in brain histone acetylation in the transgenic mice that may reflect an indirect transcriptional repression underlying memory impairment. The administration of 4-PBA restored brain histone acetylation levels and, as a most likely consequence, activated the transcription of synaptic plasticity markers such as the GluR1 subunit of the AMPA receptor, PSD95, and microtubule-associated protein-2. The results suggest that 4-PBA, a drug already approved for clinical use, may provide a novel approach for the treatment of AD.
Yang, Rui; Wang, Qingjun; Li, Fang; Li, Jian; Liu, Xuewen
Oxidative stress plays important role in the pathogenesis of Alzheimer's disease (AD). Edaravone is a potent free radical scavenger that exerts antioxidant effects. Therefore, in this study we aimed to investigate neuroprotective effects of edaravone for AD. Wistar rats were randomly divided into three groups (n = 15): control group, model group, and treatment group, which were injected with phosphate buffered saline, Aβ1-40, and Aβ1-40 together with 5 mg/kg edaravone, respectively, into the right hippocampal dentate gyrus. Spatial learning and memory of the rats were examined by Morris water maze test. 4-Hydroxynonenal (4-HNE) level in rat hippocampus was analyzed by immunohistochemistry. Acetylcholinesterase (AChE) and choline acetylase (ChAT) activities were assayed by commercial kits. We found that edaravone ameliorated spatial learning and memory deficits in the rats. 4-HNE level in the hippocampus as well as AChE and ChAT activities in the hippocampus was significantly lower in treatment group than in model group. In conclusion, edaravone may be developed as a novel agent for the treatment of AD for improving cholinergic system and protecting neurons from oxidative toxicity.
Machts, Judith; Bittner, Verena; Kasper, Elisabeth; Schuster, Christina; Prudlo, Johannes; Abdulla, Susanne; Kollewe, Katja; Petri, Susanne; Dengler, Reinhard; Heinze, Hans-Jochen; Vielhaber, Stefan; Schoenfeld, Mircea A; Bittner, Daniel M
Recent work suggests that ALS and frontotemporal dementia can occur together and share at least in part the same underlying pathophysiology. However, it is unclear at present whether memory deficits in ALS stem from a temporal lobe dysfunction, or are rather driven by frontal executive dysfunction. In this study we sought to investigate the nature of memory deficits by analyzing the neuropsychological performance of 40 ALS patients in comparison to 39 amnestic mild cognitive impairment (aMCI) patients and 40 healthy controls (HC). The neuropsychological battery tested for impairment in executive functions, as well as memory and visuo-spatial skills, the results of which were compared across study groups. In addition, we calculated composite scores for memory (learning, recall, recognition) and executive functions (verbal fluency, cognitive flexibility, working memory). We hypothesized that the nature of memory impairment in ALS will be different from those exhibited by aMCI patients. Patient groups exhibited significant differences in their type of memory deficit, with the ALS group showing impairment only in recognition, whereas aMCI patients showed short and delayed recall performance deficits as well as reduced short-term capacity. Regression analysis revealed a significant impact of executive function on memory performance exclusively for the ALS group, accounting for one fifth of their memory performance. Interestingly, merging all sub scores into a single memory and an executive function score obscured these differences. The presented results indicate that the interpretation of neuropsychological scores needs to take the distinct cognitive profiles in ALS and aMCI into consideration. Importantly, the observed memory deficits in ALS were distinctly different from those observed in aMCI and can be explained only to some extent in the context of comorbid (coexisting) executive dysfunction. These findings highlight the qualitative differences in temporal lobe
Knapman, A; Heinzmann, J-M; Hellweg, R; Holsboer, F; Landgraf, R; Touma, C
Cognitive deficits are a common feature of major depression (MD), with largely unknown biological underpinnings. In addition to the affective and cognitive symptoms of MD, a dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis is commonly observed in these patients. Increased plasma glucocorticoid levels are known to render the hippocampus susceptible to neuronal damage. This structure is important for learning and memory, creating a potential link between HPA axis dysregulation and cognitive deficits in depression. In order to further elucidate how altered stress responsiveness may contribute to the etiology of MD, three mouse lines with high (HR), intermediate (IR), or low (LR) stress reactivity were generated by selective breeding. The aim of the present study was to investigate whether increased stress reactivity is associated with deficits in hippocampus-dependent memory tests. To this end, we subjected mice from the HR, IR, and LR breeding lines to tests of recognition memory, spatial memory, and depression-like behavior. In addition, measurements of brain-derived neurotrophic factor (BDNF) in the hippocampus and plasma of these animals were conducted. Our results demonstrate that HR mice exhibit hippocampus-dependent memory deficits along with decreased hippocampal, but not plasma, BDNF levels. Thus, the stress reactivity mouse lines are a promising animal model of the cognitive deficits in MD with the unique feature of a genetic predisposition for an altered HPA axis reactivity, which provides the opportunity to explore the progression of the symptoms of MD, predisposing genetic factors as well as new treatment strategies. Copyright 2009 Elsevier Ltd. All rights reserved.
Full Text Available Anosognosia, or loss of insight of memory deficits, is a common and striking symptom in Alzheimer's disease (AD. Previous findings in AD dementia patients suggest that anosognosia is due to both functional metabolic changes within cortical midline structures involved in self-referential processes, as well as functional disconnection between these regions. The present study aims to extend these findings by investigating the neural correlates of anosognosia in the prodromal stage of AD. Here, we used regional brain metabolism (resting state 18-F fluorodeoxyglucose positron emission tomography (FDG-PET to unravel the metabolic correlates of anosognosia in subjects with amnestic mild cognitive impairment (aMCI and subsequently resting state functional magnetic resonance imaging (rs-fMRI to investigate the intrinsic connectivity disruption between brain regions. Thirty-one subjects (mean age: 74.1; Clinical Dementia Rating (CDR global score: 0.5 with aMCI, and 251 cognitively normal (CN older adults (mean age: 73.3; CDR: 0 were included as a reference group for behavioral and FDG data. An anosognosia index was obtained by calculating a discrepancy score between subjective and objective memory scores. All subjects underwent FDG-PET for glucose metabolism measurement, and aMCI subjects underwent additional rs-fMRI for intrinsic connectivity measurement. Voxel-wise correlations between anosognosia and neuroimaging data were conducted in the aMCI subjects. Subjects with aMCI had significantly decreased memory awareness as compared to the CN older adults. Greater anosognosia in aMCI subjects was associated with reduced glucose metabolism in the posterior cingulate (PCC cortices and hippocampus. Intrinsic connectivity analyses revealed a significant association between anosognosia and attenuated functional connectivity between the PCC seed region and orbitofrontal cortex (OFC as well as bilateral inferior parietal lobes (IPL. These findings provide further
Full Text Available Xudong Liu,1,* Yuchao Zhang,1,* Jinquan Li,1 Dong Wang,1 Yang Wu,1 Yan Li,2 Zhisong Lu,3 Samuel CT Yu,4 Rui Li,1 Xu Yang1 1Laboratory of Environmental Biomedicine, Hubei Key Laboratory of Genetic Regulation and Integrative Biology, College of Life Science, Central China Normal University, Wuhan, People's Republic of China; 2Chemical and Biomolecular Engineering Department, Hong Kong University of Science and Technology, Hong Kong Special Administrative Region; 3Institute for Clean Energy and Advanced Materials, Southwest University, Chongqing, People's Republic of China; 4Division of Environment, Hong Kong University of Science and Technology, Hong Kong Special Administrative Region *These authors contributed equally to this work Abstract: Single-walled carbon nanotubes (SWCNTs have shown increasing promise in the field of biomedicine, especially in applications related to the nervous system. However, there are limited studies available on the neurotoxicity of SWCNTs used in vivo. In this study, neurobehavioral changes caused by SWCNTs in mice and oxidative stress were investigated. The results of ethological analysis (Morris water maze and open-field test, brain histopathological examination, and assessments of oxidative stress (reactive oxygen species [ROS], malondialdehyde [MDA], and glutathione [GSH], inflammation (nuclear factor κB, tumor necrosis factor a, interleukin-1β, and apoptosis (cysteine-aspartic acid protease 3 in brains showed that 6.25 and 12.50 mg/kg/day SWCNTs in mice could induce cognitive deficits and decreased locomotor activity, brain histopathological alterations, and increased levels of oxidative stress, inflammation, and apoptosis in mouse brains; however, 3.125 mg/kg/day SWCNTs had zero or minor adverse effects in mice, and these effects were blocked by concurrent administration of ascorbic acid. Down-regulation of oxidative stress, inflammation, and apoptosis were proposed to explain the neuroprotective effects of
Torres, Alejandro; Olivares, Jose M; Rodriguez, Angel; Vaamonde, Antonio; Berrios, German E
The objective of the study was to evaluate from the perspective of the Piaget developmental model the cognitive functioning of a sample of patients diagnosed with schizophrenia. Fifty patients with schizophrenia (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition) and 40 healthy matched controls were evaluated by means of the Longeot Logical Thought Evaluation Scale. Only 6% of the subjects with schizophrenia reached the "formal period," and 70% remained at the "concrete operations" stage. The corresponding figures for the control sample were 25% and 15%, respectively. These differences were statistically significant. The samples were specifically differentiable on the permutation, probabilities, and pendulum tests of the scale. The Longeot Logical Thought Evaluation Scale can discriminate between subjects with schizophrenia and healthy controls.
E Berg, John
Electroconvulsive treatment (ECT) has developed over 70 years to a modern, effective way of lifting depressive moods. Memory loss and visual acuity after electroconvulsive treatment is the only remaining relevant criticism of the treatment modality when considering the overall rate of remission from this treatment compared to all other treatment modalities. A depressive state impedes memory, and memory improves on several qualities of cognition after treatment. However, the comparison of a person's memory ability from the months before depression started to the level after a course of ECT is never performed, for obvious reasons. Some infectious diseases are known to influence memory negatively through effects on the dopamine receptors. More specifically, former toxoplasmosis infection may be a factor. Preliminary data on titres of toxoplasma IgG may indicate a connection to the development of long-standing memory problems after ECT.
Xu, Xiaofeng; Zhang, Bin; Lu, Kaili; Deng, Jiangshan; Zhao, Fei; Zhao, Bing-Qiao; Zhao, Yuwu
Dextromethorphan (DM) is a non-competitive antagonist of NMDA receptors and a widely used component of cough medicine. Recently, its indication has been extended experimentally to a wide range of disorders including inflammation-mediated central nervous system disorders such as Parkinson disease (PD) and multiple sclerosis (MS). In this study, we investigate whether DM treatment has protective effects on the hippocampal neuron damage induced by bilateral occlusion of the common carotid arteries (two-vessel occlusion [2VO]), an animal model of vascular dementia (VaD). Sprague-Dawley (SD) (10 weeks of age) rats were subjected to the 2VO, and DM was injected intraperitoneally once per day for 37 days. Neuron death, glial activation, and cognitive function were assessed at 37 days after 2VO (0.2 mg/kg, i.p., "DM-0.2" and 2 mg/kg, i.p., "DM-2"). DM-2 treatment provided protection against neuronal death and glial activation in the hippocampal CA1 subfield and reduced cognitive impairment induced by 2VO in rats. The study also demonstrates that activation of the Nrf2-HO-1 pathway and upregulation of superoxide dismutase (SOD) play important roles in these effects. These results suggest that DM is effective in treating VaD and protecting against oxidative stress, which is strongly implicated in the pathogenesis of VaD. Therefore, the present study suggests that DM treatment may represent a new and promising protective strategy for treating VaD.
Dermody, Nadene; Wong, Stephanie; Ahmed, Rebekah; Piguet, Olivier; Hodges, John R; Irish, Muireann
Loss of empathy is a core presenting feature of the behavioral-variant of frontotemporal dementia (bvFTD), resulting in socioemotional difficulties and behavioral transgressions. In contrast, interpersonal functioning remains relatively intact in Alzheimer's disease (AD), despite marked cognitive decline. The neural substrates mediating these patterns of loss and sparing in social functioning remain unclear, yet are relevant for our understanding of the social brain. We investigated cognitive versus affective aspects of empathy using the Interpersonal Reactivity Index (IRI) in 25 AD and 24 bvFTD patients and contrasted their performance with 22 age- and education-matched controls. Cognitive empathy was comparably compromised in AD and bvFTD, whereas affective empathy was impaired exclusively in bvFTD. While controlling for overall cognitive dysfunction ameliorated perspective-taking deficits in AD, empathy loss persisted across cognitive and affective domains in bvFTD. Voxel-based morphometry analyses revealed divergent neural substrates of empathy loss in each patient group. Perspective-taking deficits correlated with predominantly left-sided temporoparietal atrophy in AD, whereas widespread bilateral frontoinsular, temporal, parietal, and occipital atrophy was implicated in bvFTD. Reduced empathic concern in bvFTD was associated with atrophy in the left orbitofrontal, inferior frontal, and insular cortices, and the bilateral mid-cingulate gyrus. Our findings suggest that social cognitive deficits in AD arise largely as a consequence of global cognitive dysfunction, rather than a loss of empathy per se. In contrast, loss of empathy in bvFTD reflects the deterioration of a distributed network of frontoinsular and temporal structures that appear crucial for monitoring and processing social information.
Full Text Available Oxidative stress and inflammation play a role in cognitive impairment, which is a core symptom of schizophrenia. Furthermore, a hallmark of the pathophysiology of this disease is the dysfunction of cortical inhibitory γ-aminobutyric acid (GABA neurons expressing parvalbumin (PV, which is also involved in cognitive impairment. Sulforaphane (SFN, an isothiocyanate derived from broccoli, is a potent activator of the transcription factor Nrf2, which plays a central role in the inducible expressions of many cytoprotective genes in response to oxidative stress. Keap1 is a cytoplasmic protein that is essential for the regulation of Nrf2 activity. Here, we found that pretreatment with SFN attenuated cognitive deficits, the increase in 8-oxo-dG-positive cells, and the decrease in PV-positive cells in the medial prefrontal cortex and hippocampus after repeated administration of phencyclidine (PCP. Furthermore, PCP-induced cognitive deficits were improved by the subsequent subchronic administration of SFN. Interestingly, the dietary intake of glucoraphanin (a glucosinolate precursor of SFN during the juvenile and adolescence prevented the onset of PCP-induced cognitive deficits as well as the increase in 8-oxo-dG-positive cells and the decrease in PV-positive cells in the brain at adulthood. Moreover, the NRF2 gene and the KEAP1 gene had an epistatic effect on cognitive impairment (e.g., working memory and processing speed in patients with schizophrenia. These findings suggest that SFN may have prophylactic and therapeutic effects on cognitive impairment in schizophrenia. Therefore, the dietary intake of SFN-rich broccoli sprouts during the juvenile and adolescence may prevent the onset of psychosis at adulthood.
Orchard, Tonya S; Gaudier-Diaz, Monica M; Weinhold, Kellie R; Courtney DeVries, A
Cancer treatments such as chemotherapy have been an important part of extending survival in women diagnosed with breast cancer. However, chemotherapy can cause potentially toxic side effects in the brain that impair memory, verbal fluency, and processing speed in up to 30% of women treated. Women report that post-chemotherapy cognitive deficits negatively impact quality of life and may last up to ten years after treatment. Mechanisms underlying these cognitive impairments are not fully understood, but emerging evidence suggests that chemotherapy induces structural changes in the brain, produces neuroinflammation, and reduces adult hippocampal neurogenesis. Dietary approaches that modify inflammation and neurogenesis are promising strategies for reducing chemotherapy-induced cognitive deficits in breast cancer survivors. In this review, we describe the cognitive and neuronal side effects associated with commonly used chemotherapy treatments for breast cancer, and we focus on the often opposing actions of omega-3 fatty acids and added sugars on cognitive function, neuroinflammation, and adult hippocampal neurogenesis. Omega-3 fatty acids administered concurrently with doxorubicin chemotherapy have been shown to prevent depressive-like behaviors and reduce neuroinflammation, oxidative stress, and neural apoptosis in rodent models. In contrast, diets high in added sugars may interact with n-3 FAs to diminish their anti-inflammatory activity or act independently to increase neuroinflammation, reduce adult hippocampal neurogenesis, and promote cognitive deficits. We propose that a diet rich in long-chain, marine-derived omega-3 fatty acids and low in added sugars may be an ideal pattern for preventing or alleviating neuroinflammation and oxidative stress, thereby protecting neurons from the toxic effects of chemotherapy. Research testing this hypothesis could lead to the identification of modifiable dietary choices to reduce the long-term impact of chemotherapy on the
Full Text Available Abstract Background On average, health worsens with age, but many people have periods of improvement. A stochastic model provides an excellent description of how such changes occur. Given that cognition also changes with age, we wondered whether the same model might also describe the accumulation of errors in cognitive test scores in community-dwelling older adults. Methods In this prospective cohort study, 8954 older people (aged 65+ at baseline from the Canadian Study of Health and Aging were followed for 10 years. Cognitive status was defined by the number of errors on the 100-point Modified Min-Mental State Examination. The error count was chosen to parallel the deficit count in the general model of aging, which is based on deficit accumulation. As with the deficit count, a Markov chain transition model was employed, with 4 parameters. Results On average, the chance of making errors increased linearly with the number of errors present at each time interval. Changes in cognitive states were described with high accuracy (R2 = 0.96 by a modified Poisson distribution, using four parameters: the background chance of accumulating additional errors, the chance of incurring more or fewer errors, given the existing number, and the corresponding background and incremental chances of dying. Conclusion The change in the number of errors in a cognitive test corresponded to a general model that also summarizes age-related changes in deficits. The model accounts for both improvement and deterioration and appears to represent a clinically relevant means of quantifying how various aspects of health status change with age.
Zagreda, L; Goodman, J; Druin, D P; McDonald, D; Diamond, A
Phenylalanine hydroxylase (Pah)-deficient "PKU mice" have a mutation in the Pah gene that causes phenylketonuria (PKU) in humans. PKU produces cognitive deficits in humans if it is untreated. We report here the first evidence that the genetic mouse model of PKU (Pah(enu2)) also produces cognitive impairments. PKU mice were impaired on both odor discrimination reversal and latent learning compared with heterozygote littermates and with wild-type mice of the same BTBR strain. A small container of cinnamon-scented sand was presented on the right or left, and nutmeg-scented sand was presented on the other side; left-right location varied over trials. Digging in sand of the correct scent was rewarded by finding phenylalanine-free chocolate. To prevent scent cuing, new containers were used on every trial, and both containers always contained chocolate. Digging in the incorrect choice was stopped before the chocolate was uncovered. Once criterion was reached, the other scent was rewarded. PKU mice were impaired on reversals 2, 3, and 4. They were also impaired in latent learning. On day 1, half the mice were allowed to explore a maze and discover the location of water. On day 2, all mice were water-deprived and were placed in the maze. Whereas pre-exposed wild-type and heterozygous mice showed evidence that they remembered the location of the water and hence could find the water faster on day 2, pre-exposed PKU mice showed no significant benefit from their pre-exposure on day 1.
In a previous study, we detected a 6p25-p24 region linked to schizophrenia in families with high composite cognitive deficit (CD) scores, a quantitative trait integrating multiple cognitive measures. Association mapping of a 10 Mb interval identified a 260 kb region with a cluster of single-nucleotide polymorphisms (SNPs) significantly associated with CD scores and memory performance. The region contains two colocalising genes, LYRM4 and FARS2, both encoding mitochondrial proteins. The two tagging SNPs with strongest evidence of association were located around the overlapping putative promoters, with rs2224391 predicted to alter a transcription factor binding site (TFBS). Sequencing the promoter region identified 22 SNPs, many predicted to affect TFBSs, in a tight linkage disequilibrium block. Luciferase reporter assays confirmed promoter activity in the predicted promoter region, and demonstrated marked downregulation of expression in the LYRM4 direction under the haplotype comprising the minor alleles of promoter SNPs, which however is not driven by rs2224391. Experimental evidence from LYRM4 expression in lymphoblasts, gel-shift assays and modelling of DNA breathing dynamics pointed to two adjacent promoter SNPs, rs7752203-rs4141761, as the functional variants affecting expression. Their C-G alleles were associated with higher transcriptional activity and preferential binding of nuclear proteins, whereas the G-A combination had opposite effects and was associated with poor memory and high CD scores. LYRM4 is a eukaryote-specific component of the mitochondrial biogenesis of Fe-S clusters, essential cofactors in multiple processes, including oxidative phosphorylation. LYRM4 downregulation may be one of the mechanisms involved in inefficient oxidative phosphorylation and oxidative stress, increasingly recognised as contributors to schizophrenia pathogenesis.Molecular Psychiatry advance online publication, 4 October 2011; doi:10.1038\\/mp.2011.129.
Full Text Available Alzheimer’s disease (AD is a multi-factorial neurodegenerative disorder with abnormal accumulation of amyloid-β (Aβ plaques, neuroinflammation and impaired neurogenesis. Mounting evidences suggest that single-target drugs have limited effects on clinical treatment and alternative or multiple targets are required. In recent decades, natural compounds and their derivatives have gained increasing attention in AD drug discovery due to their inherently enormous chemical and structural diversity. In this study, we demonstrated that naringin dihydrochalcone (NDC, a widely used dietary sweetener with strong antioxidant activity, improved the cognitive function of transgenic AD mice. Pathologically, NDC attenuated Aβ deposition in AD mouse brain. Furthermore, NDC reduced periplaque activated microglia and astrocytes, indicating the inhibition of neuroinflammation. It also enhanced neurogenesis as investigated by BrdU/NeuN double labeling. Additionally, the inhibition of Aβ level and neuroinflammation by NDC treatment was also observed in an AD cell model or a microglia cell line. Taken together, our study indicated that NDC might be a potential therapeutic agent for the treatment of AD against multiple targets that include Aβ pathology, neuroinflammation and neurogenesis.
Full Text Available It has been suggested that changes in some event-related potential (ERP parameters associated with controlled processing of stimuli could be used as biomarkers of amnestic mild cognitive impairment (aMCI. However, data regarding the suitability of ERP components associated with automatic and involuntary processing of stimuli for this purpose are not conclusive. In the present study, we studied the Mismatch Negativity (MMN component, a correlate of the automatic detection of changes in the acoustic environment, in healthy adults and adults with aMCI (age range: 50-87 years. An auditory-visual attention-distraction task, in two evaluations separated by an interval of between 18 and 24 months, was used. In both evaluations, the MMN amplitude was significantly smaller in the aMCI adults than in the control adults. In the first evaluation, such differences were observed for the subgroup of adults between 50 and 64 years of age, but not for the subgroup of 65 years and over. In the aMCI adults, the MMN amplitude was significantly smaller in the second evaluation than in the first evaluation, but no significant changes were observed in the control adult group. The MMN amplitude was found to be a sensitive and specific biomarker of aMCI, in both the first and second evaluation.
Pukhal'skiĭ, A L; Shmarina, G V; Aleshkin, V A
The concept of stressful cognitive dysfunction, which is under consideration in this review, allows picking out several therapeutic targets. The brain, immune and endocrine systems being the principal adaptive systems in the body permanently share information both in the form of neural impulses and soluble mediators. The CNS differs from other organs due to several peculiarities that affect local immune surveillance. The brain cells secluded from the blood flow by a specialized blood-brain-barrier (BBB) can endogenously express pro- and anti-inflammatory cytokines without the intervention of the immune system. In normal brain the cytokine signaling rather contributes to exclusive brain function (e.g. long-term potentiation, synaptic plasticity, adult neurogenesis) than serves as immune communicator. The stress of different origin increases the serum cytokine levels and disrupts BBB. As a result peripheral cytokines penetrate into the brain where they begin to perform new functions. Mass intrusion of biologically active peptides having a lot of specific targets alters the brain work that we can observe both in humans and in animal experiments. In addition owing to BBB disruption dendritic cells and T cells also penetrate into the brain where they take up a perivascular position. The changes observed in stressed subject may accumulate during repeated episodes of stress forming a picture typical of the aging brain. Moreover long-term stress as well as physiological aging result in hormonal and immunological disturbances including hypothalamic-pituitary-adrenal axis depletion, regulatory T-cell accumulation and dehydroepiandrosterone decrease.
Full Text Available The present study was designed to probe the effects of Huperzine A (HupA on diabetes-associated cognitive decline (DACD using a streptozotocin (STZ-injected rat model. Diabetic rats were treated with HupA (0.05 and 0.1 mg/kg for seven weeks. Memory functions were evaluated by the water maze test. Nissl staining was selected for detecting neuronal loss. Protein and mRNA levels of brain-derived neurotrophic factor (BDNF were analyzed by ELISA and real-time PCR, respectively. The activities of choline acetylase (ChAT, Acetylcholinesterase (AChE, malondialdehyde (MDA, superoxide dismutase (SOD, glutathione peroxidase (GSH-Px, catalase (CAT, NF-κB p65 unit, TNF-α, IL-1β, IL-6 and caspase-3 were measured using corresponding kits. After seven weeks, diabetic rats exhibited remarkable reductions in: body weight, percentage of time spent in target quadrant, number of times crossing the platform, ChAT and BDNF levels, SOD, GSH-Px and CAT accompanied with increases in neuronal damage, plasma glucose levels, escape latency, mean path length, AChE, MDA level as well as CAT, NF-κB p65 unit, TNF-α, IL-1β, IL-6 and caspase-3 in cerebral cortex and hippocampus. Supplementation with HupA significantly and dose-dependently reversed the corresponding values in diabetes. It is concluded that HupA ameliorates DACD via modulating BDNF, oxidative stress, inflammation and apoptosis.
Mao, Xiao-Yuan; Cao, Dan-Feng; Li, Xi; Yin, Ji-Ye; Wang, Zhi-Bin; Zhang, Ying; Mao, Chen-Xue; Zhou, Hong-Hao; Liu, Zhao-Qian
The present study was designed to probe the effects of Huperzine A (HupA) on diabetes-associated cognitive decline (DACD) using a streptozotocin (STZ)-injected rat model. Diabetic rats were treated with HupA (0.05 and 0.1 mg/kg) for seven weeks. Memory functions were evaluated by the water maze test. Nissl staining was selected for detecting neuronal loss. Protein and mRNA levels of brain-derived neurotrophic factor (BDNF) were analyzed by ELISA and real-time PCR, respectively. The activities of choline acetylase (ChAT), Acetylcholinesterase (AChE), malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase (CAT), NF-κB p65 unit, TNF-α, IL-1β, IL-6 and caspase-3 were measured using corresponding kits. After seven weeks, diabetic rats exhibited remarkable reductions in: body weight, percentage of time spent in target quadrant, number of times crossing the platform, ChAT and BDNF levels, SOD, GSH-Px and CAT accompanied with increases in neuronal damage, plasma glucose levels, escape latency, mean path length, AChE, MDA level as well as CAT, NF-κB p65 unit, TNF-α, IL-1β, IL-6 and caspase-3 in cerebral cortex and hippocampus. Supplementation with HupA significantly and dose-dependently reversed the corresponding values in diabetes. It is concluded that HupA ameliorates DACD via modulating BDNF, oxidative stress, inflammation and apoptosis. PMID:24857910
Agay, Nirit; Yechiam, Eldad; Carmel, Ziv; Levkovitz, Yechiel
We compare the view that the effect of methylphenidate (MPH) is selective to individuals with attention-deficit/hyperactivity disorder (ADHD) with an alternative approach suggesting that its effect is more prominent for individuals with weak baseline capacities in relevant cognitive tasks. To evaluate theses 2 approaches, we administered sustained attention, working memory, and decision-making tasks to 20 ADHD adults and 19 control subjects, using a within-subject placebo-controlled design. The results demonstrated no main effects of MPH in the decision-making tasks. In the sustained attention and working-memory tasks, MPH enhanced performance of both ADHD and non-ADHD adults to a similar extent compared with placebo. Hence, the effect of MPH was not selective to ADHD adults. In addition, those benefitting most from MPH in all 3 task domains tended to be individuals with poor task performance. However, in most tasks, individuals whose performance was impaired by MPH were not necessarily better (or worse) performers. The findings suggest that the administration of MPH to adults with ADHD should consider not only clinical diagnosis but also their functional (performance-based) profile.
Biscaldi, M; Bednorz, N; Weissbrodt, K; Saville, C W N; Feige, B; Bender, S; Klein, C
Autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) have previously been studied mainly in isolation from each other. However the two conditions may be aetiologically related and thus show overlap in aetiologically relevant functions. In order to address this question of potential aetiological overlap between ADHD and ASD, the present study set out to investigate putative endophenotypes of ADHD in N=33 typically developing (TD) children and N=28 patients with ASD that were (ASD+) or were not (ASD-) co-morbid for ADHD. With regard to both the cognitive endophenotype candidates (working memory, inhibition, temporal processing) and intra-subject variability (ISV) the pattern of abnormalities was inconsistent. Furthermore, the overall profile of ASD-TD differences was extremely similar to the pattern of differences between the ASD+ and ASD- sub-groups, suggesting that any abnormalities found were due to the comorbid ASD subgroup. This held in particular for ISV, which did not show in patients with ASD the task-general increase that is common in ADHD samples. Altogether, the present results do not support the hypothesis of aetiological overlap between ASD and ADHD. Copyright © 2016 Elsevier B.V. All rights reserved.
Schoenberg, Poppy L A; Hepark, Sevket; Kan, Cornelis C; Barendregt, Henk P; Buitelaar, Jan K; Speckens, Anne E M
To examine whether mindfulness-based cognitive therapy (MBCT) would enhance attenuated amplitudes of event-related potentials (ERPs) indexing performance monitoring biomarkers of attention-deficit/hyperactivity disorder (ADHD). Fifty adult ADHD patients took part in a randomised controlled study investigating ERP and clinical measures pre-to-post MBCT. Twenty-six patients were randomly allocated to MBCT, 24 to a wait-list control. Main outcome measures included error processing (ERN, Pe), conflict monitoring (NoGo-N2), and inhibitory control (NoGo-P3) ERPs concomitant to a continuous performance task (CPT-X). Inattention and hyperactivity-impulsivity ADHD symptoms, psychological distress and social functioning, and mindfulness skills were also assessed. MBCT was associated with increased Pe and NoGo-P3 amplitudes, coinciding with reduced 'hyperactivity/impulsivity' and 'inattention' symptomatology. Specific to the MBCT; enhanced Pe amplitudes correlated with a decrease in hyperactivity/impulsivity symptoms and increased 'act-with-awareness' mindfulness skill, whereas, enhanced P3 correlated with amelioration in inattention symptoms. MBCT enhanced ERP amplitudes associated with motivational saliency and error awareness, leading to improved inhibitory regulation. MBCT suggests having comparable modulation on performance monitoring ERP amplitudes as pharmacological treatments. Further study and development of MBCT as a treatment for ADHD is warranted, in addition to its potential scope for clinical applicability to broader defined externalising disorders and clinical problems associated with impairments of the prefrontal cortex. Copyright © 2013 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.
Diestel, Stefan; Schmidt, Klaus-Helmut
The present study examines whether cognitive control deficits (CCDs) as a personal vulnerability factor amplify the relationship between emotional dissonance (ED; perceived discrepancy between felt and expressed emotions) and burnout symptoms (emotional exhaustion and depersonalization) as well as absenteeism. CCDs refer to daily failures and impairments of attention regulation, impulse control, and memory. The prediction of the moderator effect of CCDs draws on the argument that portraying emotions which are not genuinely felt is a form of self-regulation taxing and depleting a limited resource capacity. Interindividual differences in the resource capacity are reflected by the measure of CCDs. Drawing on two German samples (one cross-sectional and one longitudinal sample; NTOTAL = 645) of service employees, the present study analyzed interactive effects of ED and CCDs on exhaustion, depersonalization, and two indicators of absenteeism. As was hypothesized, latent moderated structural equation modeling revealed that the adverse impacts of ED on both burnout symptoms and absence behavior were amplified as a function of CCDs. Theoretical and practical implications of the present results will be discussed.
Min Young Park
Full Text Available PMC-12 is a prescription used in traditional Korean medicine that consists of a mixture of four herbal medicines, Polygonum multiflorum, Rehmannia glutinosa, Polygala tenuifolia, and Acorus gramineus, which have been reported to have various pharmacological effects on age-related neurological diseases. In the present study, we investigated whether PMC-12 improves cognitive deficits associated with decreased neuroinflammation in an amyloid-β-(Aβ- induced mouse model and exerts the antineuroinflammatory effects in lipopolysaccharide-(LPS- stimulated murine BV2 microglia. Intracerebroventricular injection of Aβ25-35 in mice resulted in impairment in learning and spatial memory, whereas this was reversed by oral administration of PMC-12 (100 and 500 mg/kg/day in dose-dependent manners. Moreover, PMC-12 reduced the increase of Aβ expression and activation of microglia and astrocytes in the Aβ25-35-injected brain. Furthermore, quantitative PCR data showed that inflammatory mediators were significantly decreased by administration of PMC-12 in Aβ-injected brains. Consistent with the in vivo data, PMC-12 significantly reduced the inflammatory mediators in LPS-stimulated BV2 cells without cell toxicity. Moreover, PMC-12 exhibited anti-inflammatory properties via downregulation of ERK, JNK, and p38 MAPK pathways. These findings suggest that the protective effects of PMC-12 may be mediated by its antineuroinflammatory activities, resulting in the attenuation of memory impairment; accordingly, PMC-12 may be useful in the prevention and treatment of AD.
Del Sole, Angelo; Lecchi, Michela; Lucignani, Giovanni; Clerici, Francesca; Mariani, Claudio; Maggiore, Laura; Chiti, Arturo; Mosconi, Lisa
The purpose of the study was the identification of group and individual subject patterns of cerebral glucose metabolism (CMRGlu) in patients with Alzheimer's disease (AD) and with amnestic mild cognitive impairment (aMCI). [ 18 F]fluorodeoxyglucose positron emission tomography (PET) studies and neuropsychological tests were performed in 16 aMCI patients (ten women, age 75 ± 8 years) and in 14 AD patients (ten women, age 75 ± 9 years). Comparisons between patient subgroups and with a control population were performed using Statistical Parametric Mapping. Clusters of low CMRGlu were observed bilaterally in the posterior cingulate cortex (PCC), in the precuneus, in the inferior parietal lobule and middle temporal gyrus of AD patients. In aMCI patients, reduced CMRGlu was found only in PCC. Areas of low CMRGlu in PCC were wider in AD compared to aMCI and extended to the precuneus, while low CMRGlu was found in the lateral parietal cortex in AD but not in aMCI patients. Individual subject pattern analysis revealed that 86% of AD patients had low CMRGlu in the PCC (including the precuneus in 71%), 71% in the temporal cortex, 64% in the parietal cortex and 35% in the frontal cortex. Among the aMCI patients, 56% had low CMRGlu in the PCC, 44% in the temporal cortex, 18% in the frontal cortex and none in the parietal cortex. This study demonstrates that both AD and aMCI patients have highly heterogeneous metabolic impairment. This potential of individual metabolic PET imaging in patients with AD and aMCI may allow timely identification of brain damage on individual basis and possibly help planning tailored early interventions. (orig.)
Full Text Available Studies on first responders who are repeatedly exposed to traumatic events report low levels of PTSD symptoms and diagnosis. However, neuroimaging and behavioral studies show that traumatic exposure is associated with brain and cognitive dysfunctions. Taking together it may suggest that traumatic exposure have a price, which is not sufficiently defined by the standard PTSD measures. In a recent study we revealed that similar to individuals with PTSD, non-PTSD highly exposed firefighters display a selective impairment in hippocampal related functions. In the current study we aimed to test whether different first responders display a similar impairment. We concentrated on unique populations of active duty firefighters and criminal scene-investigators (CSI police, who are frequently exposed to similar levels and types of traumatic events, and compared them to civilian matched-controls with no history of trauma-exposure. We used a hippocampal dependent cue-context reversal paradigm, which separately evaluates reversal of negative and positive outcomes of cue and context related information. We predicted and found that all participants were equally able to acquire and retain stimulus-outcome associations. However, there were significant differences in reversal learning between the groups. Performance among firefighters replicated our prior findings; they struggled to learn that a previously negative context is later associated with a positive outcome. CSI police on the other hand showed a selective impairment in reversing the outcome of a negative cue. Hence after learning that a specific cue is associated with a negative outcome, they could not learn that later it is associated with a positive outcome. Performance in both groups did not correlate with levels of PTSD, anxiety, depression or behavioral inhibition symptoms. The results provide further evidence of the hidden price of traumatic exposure, suggesting that this price may differ as a
Pellicano, Elizabeth; Maybery, Murray; Durkin, Kevin; Maley, Alana
This study examined the validity of "weak" central coherence (CC) in the context of multiple cognitive capabilities/deficits in autism. Children with an autism spectrum disorder (ASD) and matched typically developing children were administered tasks tapping visuospatial coherence, false-belief understanding and aspects of executive control. Significant group differences were found in all three cognitive domains. Evidence of local processing on coherence tasks was widespread in the ASD group, but difficulties in attributing false beliefs and in components of executive functioning were present in fewer of the children with ASD. This cognitive profile was generally similar for younger and older children with ASD. Furthermore, weak CC was unrelated to false-belief understanding, but aspects of coherence (related to integration) were associated with aspects of executive control. Few associations were found between cognitive variables and indices of autistic symptomatology. Implications for CC theory are discussed.
Yorifuji, Takashi; Debes, Frodi; Weihe, Pal
1986-1987 from whom lead was measured in cord-blood. A total of 896 cohort subjects participated in a clinical examination at age 7 and 808 subjects in a second examination at age 14. We evaluated the association between cord-blood lead concentrations and cognitive deficits (attention/working memory......, language, visuospatial, and memory) using multiple regression models. Overall, the lead concentration showed no clear pattern of association. However, in subjects with a low methylmercury exposure, after inclusion of statistical interaction terms, lead-associated adverse effects on cognitive functions were...
Zenouzi, Roman; von der Gablentz, Janina; Heldmann, Marcus; Göttlich, Martin; Weiler-Normann, Christina; Sebode, Marcial; Ehlken, Hanno; Hartl, Johannes; Fellbrich, Anja; Siemonsen, Susanne; Schramm, Christoph; Münte, Thomas F; Lohse, Ansgar W
In primary biliary cholangitis (PBC) fatigue is a major clinical challenge of unknown etiology. By demonstrating that fatigue in PBC is associated with an impaired cognitive performance, previous studies have pointed out the possibility of brain abnormalities underlying fatigue in PBC. Whether structural brain changes are present in PBC patients with fatigue, however, is unclear. To evaluate the role of structural brain abnormalities in PBC patients severely affected from fatigue we, therefore, performed a case-control cerebral magnetic resonance imaging (cMRI) study and correlated changes of white and grey brain matter with the cognitive and attention performance. 20 female patients with PBC and 20 female age-matched controls were examined in this study. The assessment of fatigue, psychological symptoms, cognitive and attention performance included clinical questionnaires, established cognition tests and a computerized test battery of attention performance. T1-weighted cMRI and diffusion tensor imaging (DTI) scans were acquired with a 3 Tesla scanner. Structural brain alterations were investigated with voxel-based morphometry (VBM) and DTI analyses. Results were correlated to the cognitive and attention performance. Compared to healthy controls, PBC patients had significantly higher levels of fatigue and associated psychological symptoms. Except for an impairment of verbal fluency, no cognitive or attention deficits were found in the PBC cohort. The VBM and DTI analyses revealed neither major structural brain abnormalities in the PBC cohort nor correlations with the cognitive and attention performance. Despite the high burden of fatigue and selected cognitive deficits, the attention performance of PBC patients appears to be comparable to healthy people. As structural brain alterations do not seem to be present in PBC patients with fatigue, fatigue in PBC must be regarded as purely functional. Future studies should evaluate, whether functional brain changes
Full Text Available In primary biliary cholangitis (PBC fatigue is a major clinical challenge of unknown etiology. By demonstrating that fatigue in PBC is associated with an impaired cognitive performance, previous studies have pointed out the possibility of brain abnormalities underlying fatigue in PBC. Whether structural brain changes are present in PBC patients with fatigue, however, is unclear. To evaluate the role of structural brain abnormalities in PBC patients severely affected from fatigue we, therefore, performed a case-control cerebral magnetic resonance imaging (cMRI study and correlated changes of white and grey brain matter with the cognitive and attention performance.20 female patients with PBC and 20 female age-matched controls were examined in this study. The assessment of fatigue, psychological symptoms, cognitive and attention performance included clinical questionnaires, established cognition tests and a computerized test battery of attention performance. T1-weighted cMRI and diffusion tensor imaging (DTI scans were acquired with a 3 Tesla scanner. Structural brain alterations were investigated with voxel-based morphometry (VBM and DTI analyses. Results were correlated to the cognitive and attention performance.Compared to healthy controls, PBC patients had significantly higher levels of fatigue and associated psychological symptoms. Except for an impairment of verbal fluency, no cognitive or attention deficits were found in the PBC cohort. The VBM and DTI analyses revealed neither major structural brain abnormalities in the PBC cohort nor correlations with the cognitive and attention performance.Despite the high burden of fatigue and selected cognitive deficits, the attention performance of PBC patients appears to be comparable to healthy people. As structural brain alterations do not seem to be present in PBC patients with fatigue, fatigue in PBC must be regarded as purely functional. Future studies should evaluate, whether functional brain
Full Text Available Introduction: There is increasing evidence for the involvement of chronic inflammation and oxidative stress in the pathogenesis of Alzheimer's disease (AD. Nuclear factor erythroid 2-related factor 2 (Nrf2 is an anti-inflammatory transcription factor that regulates the oxidative stress defense. Our previous experiments demonstrated that kavalactones protect neuronal cells against Amyloid β (Aβ-induced oxidative stress in vitro by Nrf2 pathway activation. Here, we tested an in vivo kavalactone treatment in a mouse model of AD. Methods: The kavalactone methysticin was administered once a week for a period of 6 months to 6 month old transgenic APP/Psen1 mice by oral gavage. Nrf2 pathway activation was measured by methysticin treatment of ARE-luciferase mice, by qPCR of Nrf2-target genes and immunohistochemical detection of Nrf2. Aβ burden was analyzed by CongoRed staining, immunofluorescent detection and ELISA. Neuroinflammation was assessed by immunohistochemical stainings for microglia and astrocytes. Pro-inflammatory cytokines in the hippocampus was determined by Luminex multi-plex assays. The hippocampal oxidative damage was detected by oxyblot technique and immunohistochemical staining against DT3 and 4-HNE. The cognitive ability of mice was evaluated using Morris water maze. Results: Methysticin treatment activated the Nrf2 pathway in the hippocampus and cortex of mice. The Aβ deposition in brains of methysticin-treated APP/Psen1 mice was not altered compared to untreated mice. However, methysticin treatment significantly reduced microgliosis, astrogliosis and secretion of the pro-inflammatory cytokines TNF-α and IL-17A. In addition, the oxidative damage of hippocampi from APP/Psen1 mice was reduced by methysticin treatment. Most importantly, methysticin treatment significantly attenuated the long-term memory decline of APP/Psen1 mice. Conclusion: In summary, these findings show that methysticin administration activates the Nrf2 pathway
Gong, Wei-Gang; Wang, Yan-Juan; Zhou, Hong; Li, Xiao-Li; Bai, Feng; Ren, Qing-Guo; Zhang, Zhi-Jun
Our previous experiments demonstrated that social isolation (SI) caused AD-like tau hyperphosphorylation and spatial memory deficits in middle-aged rats. However, the underlying mechanisms of SI-induced spatial memory deficits remain elusive. Middle-aged rats (10 months) were group or isolation reared for 8 weeks. Following the initial 4-week period of rearing, citalopram (10 mg/kg i.p.) was administered for 28 days. Then, pathophysiological changes were assessed by performing behavioral, biochemical, and pathological analyses. We found that SI could cause cognitive dysfunction and decrease synaptic protein (synaptophysin or PSD93) expression in different brain regions associated with cognition, such as the prefrontal cortex, dorsal hippocampus, ventral hippocampus, amygdala, and caudal putamen, but not in the entorhinal cortex or posterior cingulate. Citalopram could significantly improve learning and memory and partially restore synaptophysin or PSD93 expression in the prefrontal cortex, hippocampus, and amygdala in SI rats. Moreover, SI decreased the number of dendritic spines in the prefrontal cortex, dorsal hippocampus, and ventral hippocampus, which could be reversed by citalopram. Furthermore, SI reduced the levels of BDNF, serine-473-phosphorylated Akt (active form), and serine-9-phosphorylated GSK-3β (inactive form) with no significant changes in the levels of total GSK-3β and Akt in the dorsal hippocampus, but not in the posterior cingulate. Our results suggest that decreased synaptic plasticity in cognition-associated regions might contribute to SI-induced cognitive deficits, and citalopram could ameliorate these deficits by promoting synaptic plasticity mainly in the prefrontal cortex, dorsal hippocampus, and ventral hippocampus. The BDNF/Akt/GSK-3β pathway plays an important role in regulating synaptic plasticity in SI rats.
Bikic, Aida; Leckman, James F; Lindschou, Jane; Christensen, Torben Ø; Dalsgaard, Søren
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 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. 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 control group. The intervention group will be asked to use ACTIVATE™ at home 40 minutes per day, 6 days per week for 8 weeks. Both intervention and control group will receive treatment as usual. Outcome measures will assess cognitive functions, symptoms, and behavioral and functional measures before and after the 8 weeks of training and in a 12- and 24-week follow-up. Results of this trial will provide useful information on the effectiveness of computer training focusing on several cognitive functions. Cognitive
Full Text Available Persistent neurobehavioral deficits and brain changes need validation for brain restoration. Two hours middle cerebral artery occlusion (tMCAO or sham surgery was performed in male Sprague-Dawley rats. Neurobehavioral and cognitive deficits were measured over 10 weeks included: (1 sensory, motor, beam balance, reflex/abnormal responses, hindlimb placement, forepaw foot fault and cylinder placement tests, and (2 complex active place avoidance learning (APA and simple passive avoidance retention (PA. Electroretinogram (ERG, hemispheric loss (infarction, hippocampus CA1 neuronal loss and myelin (Luxol Fast Blue staining in several fiber tracts were also measured. In comparison to Sham surgery, tMCAO surgery produced significant deficits in all behavioral tests except reflex/abnormal responses. Acute, short lived deficits following tMCAO were observed for forelimb foot fault and forelimb cylinder placement. Persistent, sustained deficits for the whole 10 weeks were exhibited for motor (p<0.001, sensory (p<0.001, beam balance performance (p<0.01 and hindlimb placement behavior (p<0.01. tMCAO produced much greater and prolonged cognitive deficits in APA learning (maximum on last trial of 604±83% change, p<0.05 but only a small, comparative effect on PA retention. Hemispheric loss/atrophy was measured 10 weeks after tMCAO and cross-validated by two methods (e.g., almost identical % ischemic hemispheric loss of 33.4±3.5% for H&E and of 34.2±3.5% for TTC staining. No visual dysfunction by ERG and no hippocampus neuronal loss were detected after tMCAO. Fiber tract damage measured by Luxol Fast Blue myelin staining intensity was significant (p<0.01 in the external capsule and striatum but not in corpus callosum and anterior commissure. In summary, persistent neurobehavioral deficits were validated as important endpoints for stroke restorative research in the future. Fiber myelin loss appears to contribute to these long term behavioral dysfunctions and
Umbricht, D; Schmid, L; Koller, R; Vollenweider, F X; Hell, D; Javitt, D C
In patients with schizophrenia, deficient generation of mismatch negativity (MMN)-an event-related potential (ERP) indexing auditory sensory ("echoic") memory-and a selective increase of "context dependent" ("BX") errors in the "A-X" version of the Continuous Performance Test (AX-CPT) indicate an impaired ability to form and use transient memory traces. Animal and human studies implicate deficient N-methyl-D-aspartate receptor (NMDAR) functioning in such abnormalities. In this study, effects of the NMDAR antagonists ketamine on MMN generation and AX-CPT performance were investigated in healthy volunteers to test the hypothesis that NMDARs are critically involved in human MMN generation, and to assess the nature of ketamine-induced deficits in AX-CPT performance. In a single-blind placebo-controlled study, 20 healthy volunteers underwent an infusion with subanesthetic doses of ketamine. The MMN-to-pitch and MMN-to-duration deviants were obtained while subjects performed an AX-CPT. Ketamine significantly decreased the peak amplitudes of the MMN-to-pitch and MMN-to-duration deviants by 27% and 21%, respectively. It induced performance deficits in the AX-CPT characterized by decreased hit rates and specific increases of errors (BX errors), reflecting a failure to form and use transient memory traces of task relevant information. The NMDARs are critically involved in human MMN generation. Deficient MMN in schizophrenia thus suggests deficits in NMDAR-related neurotransmission. N-methyl-D-aspartate receptor dysfunction may also contribute to the impairment of patients with schizophrenia in forming and using transient memory traces in more complex tasks, such as the AX-CPT. Thus, NMDAR-related dysfunction may underlie deficits in transient memory at different levels of information processing in schizophrenia. Arch Gen Psychiatry. 2000;57:1139-1147.
Dale L. Smith
Full Text Available BackgroundNumerous studies over the past several decades have illustrated that children who suffer from sleep-disordered breathing (SDB are at greater risk for cognitive, behavioral, and psychiatric problems. Although behavioral problems have been proposed as a potential mediator between SDB and cognitive functioning, these relationships have not been critically examined.MethodsThis analysis is based on a community-based cohort of 1,115 children who underwent overnight polysomnography, and cognitive and behavioral phenotyping. Structural model of the relationships between SDB, behavior, and cognition, and two recently developed mediation approaches based on propensity score weighting and resampling were used to assess the mediational role of parent-reported behavior and psychiatric problems in the relationship between SDB and cognitive functioning. Multiple models utilizing two different SDB definitions further explored direct effects of SDB on cognition as well as indirect effects through behavioral pathology. All models were adjusted for age, sex, race, BMI z-score, and asthma status.ResultsIndirect effects of SDB through behavior problems were significant in all mediation models, while direct effects of SDB on cognition were not. The findings were consistent across different mediation procedures and remained essentially unaltered when different criteria for SDB, behavior, and cognition were used.ConclusionPotential effects of SDB on cognitive functioning appear to occur through behavioral problems that are detectable in this pediatric population. Thus, early attentional or behavioral pathology may be implicated in the cognitive functioning deficits associated with SDB, and may present an early morbidity-related susceptibility biomarker.
Zvejniece, Liga; Svalbe, Baiba; Liepinsh, Edgars; Pulks, Eduards; Dambrova, Maija
Middle cerebral artery occlusion (MCAO) is the most commonly used method to study the neurological and histological outcomes and the pathological mechanisms of ischaemic stroke. The current work compares sensorimotor and cognitive deficits and the infarct volume in rats following a transient 90- or 120-min MCAO, which allows the appropriate behavioural tests to be chosen based on the goal and design of the experiment. In the beam-walking test, we found significant differences between the 90- and 120-min MCAO groups in the number of foot faults made with the impaired hindlimb on post-stroke days 3, 7 and 14. In the cylinder test, a difference between the 90- and 120-min groups was observed on post-operation day 14. The responses to tactile and proprioceptive stimulation were impaired to a similar extent after 90- and 120-min MCAO in the vibrissae-evoked forelimb-placing and limb-placing tests. Moreover, we found significant memory impairment in the 120-min MCAO group 6 days after the acquisition trial. The brain tissue damage was significantly higher after 120-min occlusion of the MCA compared with 90-min occlusion; the infarct volumes were 13% and 25% of the contralateral hemispheres, respectively. In conclusion, both the 90- and 120-min occlusion models result in a significant impairment of sensorimotor, tactile and proprioceptive function, but memory impairment is only observed in the 120-min MCAO group. The beam-walking and cylinder tests detected neurological dysfunction after the 120-min MCAO, whereas the limb-placing and vibrissae-evoked forelimb-placing tests were able to evaluate the neurological dysfunction in rats after 90- and 120-min MCAO. Copyright © 2012 Elsevier B.V. All rights reserved.
Full Text Available Panax ginseng is a slow-growing perennial plant. Panax ginseng extract has numerous biological activities, including antitumor, anti-inflammatory and antistress activities. Panax ginseng extract also has a cognition-enhancing effect in rats with alcohol-induced memory impairment. In this study, we partially occluded the bilateral carotid arteries in the rat to induce chronic cerebral hypoperfusion, a well-known model of vascular dementia. The rats were then intragastrically administered 50 or 100 mg/kg Panax ginseng extract. Morris water maze and balance beam tests were used to evaluate memory deficits and motor function, respectively. Protein quantity was used to evaluate cholinergic neurons. Immunofluorescence staining was used to assess the number of glial fibrillary acidic protein-positive cells. Western blot assay was used to evaluate protein levels of vascular endothelial growth factor, basic fibroblast growth factor, Bcl-2 and Bax. Treatment with Panax ginseng extract for 8 weeks significantly improved behavioral function and increased neuronal density and VEGF and bFGF protein expression in the hippocampal CA3 area. Furthermore, Panax ginseng extract reduced the number of glial fibrillary acidic protein-immunoreactive cells, and it decreased apoptosis by upregulating Bcl-2 and downregulating Bax protein expression. The effect of Panax ginseng extract was dose-dependent and similar to that of nimodipine, a commonly used drug for the treatment of vascular dementia. These findings suggest that Panax ginseng extract is neuroprotective against vascular dementia induced by chronic cerebral hypoperfusion, and therefore might have therapeutic potential for preventing and treating the disease.
Milte, Catherine M; Parletta, Natalie; Buckley, Jonathan D; Coates, Alison M; Young, Ross M; Howe, Peter R C
To determine the effects of an eicosapentaenoic acid (EPA)-rich oil and a docosahexaenoic acid (DHA)-rich oil versus an ω-6 polyunsaturated fatty acid-rich safflower oil (control) on literacy and behavior in children with attention-deficit/hyperactivity disorder (ADHD) in a randomized controlled trial. Supplements rich in EPA, DHA, or safflower oil were randomly allocated for 4 mo to 90 Australian children 7 to 12 y old with ADHD symptoms higher than the 90th percentile on the Conners Rating Scales. The effect of supplementation on cognition, literacy, and parent-rated behavior was assessed by linear mixed modeling. Pearson correlations determined associations between the changes in outcome measurements and the erythrocyte fatty acid content (percentage of total) from baseline to 4 mo. There were no significant differences between the supplement groups in the primary outcomes after 4 mo. However, the erythrocyte fatty acid profiles indicated that an increased proportion of DHA was associated with improved word reading (r = 0.394) and lower parent ratings of oppositional behavior (r = 0.392). These effects were more evident in a subgroup of 17 children with learning difficulties: an increased erythrocyte DHA was associated with improved word reading (r = 0.683), improved spelling (r = 0.556), an improved ability to divide attention (r = 0.676), and lower parent ratings of oppositional behavior (r = 0.777), hyperactivity (r = 0.702), restlessness (r = 0.705), and overall ADHD symptoms (r = 0.665). Increases in erythrocyte ω-3 polyunsaturated fatty acids, specifically DHA, may improve literacy and behavior in children with ADHD. The greatest benefit may be observed in children who have comorbid learning difficulties. Copyright © 2012 Elsevier Inc. All rights reserved.
McBurnett, Keith; Villodas, Miguel; Burns, G Leonard; Hinshaw, Stephen P; Beaulieu, Allyson; Pfiffner, Linda J
We evaluated the latent structure and validity of an expanded pool of Sluggish Cognitive Tempo (SCT) items. An experimental rating scale with 44 candidate SCT items was administered to parents and teachers of 165 children in grades 2-5 (ages 7-11) recruited for a randomized clinical trial of a psychosocial intervention for Attention-Deficit/Hyperactivity Disorder, Predominantly Inattentive Type. Exploratory factor analyses (EFA) were used to extract items with high loadings (>0.59) on primary factors of SCT and low cross-loadings (0.30 or lower) on other SCT factors and on the Inattention factor of ADHD. Items were required to meet these criteria for both informants. This procedure reduced the pool to 15 items. Generally, items representing slowness and low initiative failed these criteria. SCT factors (termed Daydreaming, Working Memory Problems, and Sleepy/Tired) showed good convergent and discriminant validity in EFA and in a confirmatory model with ADHD factors. Simultaneous regressions of impairment and comorbidity on SCT and ADHD factors found that Daydreams was associated with global impairment, and Sleepy/Tired was associated with organizational problems and depression ratings, across both informants. For teachers, Daydreams also predicted ODD (inversely); Sleepy/Tired also predicted poor academic behavior, low social skills, and problem social behavior; and Working Memory Problems predicted organizational problems and anxiety. When depression, rather than ADHD, was included among the predictors, the only SCT-related associations rendered insignificant were the teacher-reported associations of Daydreams with ODD; Working Memory Problems with anxiety, and Sleepy/Tired with poor social skills. SCT appears to be meaningfully associated with impairment, even when controlling for depression. Common behaviors resembling Working Memory problems may represent a previously undescribed factor of SCT.
Luzia Flavia Coelho
Full Text Available Medication has proved highly efficacious as a means of alleviating general symptoms of attention-deficit hyperactivity disorder (ADHD. However many patients remain functionally impaired by inappropriate behavior. The present study analyzed the use of cognitive behavioral therapy (CBT with the Token Economy (TE technique to alleviate problem behavior for 25 participants with ADHD, all children (19 boys, mean age 10.11 on long-term methylphenidate medication, who were given 20 CBT sessions with 10 weeks of TE introduced as of session 5. Their ten most acute problem behaviors were selected and written records kept. On weekdays, parents recorded each inappropriate behavior and provided a suitable model for their actions. At weekly sessions, problem behaviors were counted and incident-free participants rewarded with a token. To analyze improvement (less frequent problem behavior, a list of 11 behavioral categories was rated: inattention, impulsivity, hyperactivity, disorganization, disobeying rules and routines, poor self-care, verbal/physical aggression, low frustration tolerance, compulsive behavior, antisocial behavior, lacking in initiative and distraction. Two CBT specialists categorized behaviors and an ADHD specialist ruled on discrepancies. Statistical analyses used were Generalized Estimating Equations with Poisson distribution and autoregressive order correlation structure. In the course of the sessions, problematic behaviors decreased significantly in 7 categories: impulsiveness, hyperactivity, disorganization, disobeying rules and routine, poor self-care, low frustration tolerance, compulsive behaviors, and antisocial behaviors. Caregiver attitudes to children's inappropriate behavior were discussed and reshaped. As functional improvement was observed on applying TE for 10 weeks, this type of intervention may be useful as an auxiliary strategy combined with medication.
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 with 10 weeks of TE introduced as of session 5. Their ten most acute problem behaviors were selected and written records kept. On weekdays, parents recorded each inappropriate behavior and provided a suitable model for their actions. At weekly sessions, problem behaviors were counted and incident-free participants rewarded with a token. To analyze improvement (less frequent problem behavior), a list of 11 behavioral categories was rated: inattention, impulsivity, hyperactivity, disorganization, disobeying rules and routines, poor self-care, verbal/physical aggression, low frustration tolerance, compulsive behavior, antisocial behavior, lacking in initiative and distraction. Two CBT specialists categorized behaviors and an ADHD specialist ruled on discrepancies. Statistical analyses used were Generalized Estimating Equations with Poisson distribution and autoregressive order correlation structure. In the course of the sessions, problematic behaviors decreased significantly in seven categories: impulsiveness, hyperactivity, disorganization, disobeying rules and routine, poor self-care, low frustration tolerance, compulsive behaviors, and antisocial behaviors. Caregiver attitudes to children's inappropriate behavior were discussed and reshaped. As functional improvement was observed on applying TE for 10 weeks, this type of intervention may be useful as an auxiliary strategy combined with medication.
Becker, Stephen P; Luebbe, Aaron M; Langberg, Joshua M
This study examined separate inattentive, hyperactive, and impulsive dimensions of attention-deficit/hyperactivity disorder (ADHD), as well as sluggish cognitive tempo (SCT) symptoms, in relation to college students' sleep functioning. Participants were 288 college students (ages 17-24; 65 % female; 90 % non-Hispanic White; 12 % self-reported having an ADHD diagnoses) who completed measures of ADHD/SCT symptoms and sleep functioning. Participants reported obtaining an average of 6.8 h of sleep per night (only 26 % reported obtaining ≥8 h of sleep) and having a sleep onset latency of 25 min. 63 % were classified as "poor sleepers," and poor sleepers had higher rates of ADHD and SCT symptoms than "good sleepers". Path analysis controlling for ADHD status and psychiatric medication use was used to determine associations between psychopathology and sleep functioning domains. Above and beyond covariates and other psychopathologies, hyperactivity (but not impulsivity) was significantly associated with poorer sleep quality, longer sleep latency, shorter sleep duration, and more use of sleep medications. SCT symptoms (but not inattention) were significantly associated with poorer sleep quality and increased nighttime sleep disturbance (e.g., having bad dreams, waking up in the middle of the night, feeling too cold or too hot). Both inattention and SCT were associated with greater daytime dysfunction. Regression analyses demonstrated that hyperactivity predicted sleep quality above and beyond the influence of daytime dysfunction, and inattention and SCT predicted daytime dysfunction above and beyond sleep quality. Further studies are needed to examine the interrelations of nighttime sleep functioning, ADHD/SCT, and daytime dysfunction, as well to elucidate mechanisms contributing to related functional impairments.
Full Text Available Alterations of the normal redox state can be found in all stages of schizophrenia, suggesting a key role for oxidative stress in the etiology and maintenance of the disease. Pharmacological blockade of N-methyl-D-aspartic acid (NMDA receptors can disrupt natural antioxidant defense systems and induce schizophrenia-like behaviors in animals and healthy human subjects. Perinatal administration of the NMDA receptor (NMDAR antagonist ketamine produces persistent behavioral deficits in adult mice which mimic a range of positive, negative, and cognitive symptoms that characterize schizophrenia. Here we tested whether antioxidant treatment with the glutathione (GSH precursor N-acetyl-cysteine (NAC can prevent the development of these behavioral deficits. On postnatal days (PND 7, 9 and 11, we treated mice with subanesthetic doses (30 mg/kg of ketamine or saline. Two groups (either ketamine or saline treated also received NAC throughout development. In adult animals (PND 70–120 we then assessed behavioral alterations in a battery of cognitive and psychomotor tasks. Ketamine-treated animals showed deficits in a task of cognitive flexibility, abnormal patterns of spontaneous alternation, deficits in novel-object recognition, as well as social interaction. Developmental ketamine treatment also induced behavioral stereotypy in response to an acute amphetamine challenge, and it impaired sensorimotor gating, measured as reduced prepulse inhibition (PPI of the startle response. All of these behavioral abnormalities were either prevented or strongly ameliorated by NAC co-treatment. These results suggest that oxidative stress is a major factor for the development of the ketamine-induced behavioral dysfunctions, and that restoring oxidative balance during the prodromal stage of schizophrenia might be able to ameliorate the development of several major symptoms of the disease.
Laasonen, Marja; Leppamaki, Sami; Tani, Pekka; Hokkanen, Laura
The project Adult Dyslexia and Attention Deficit Disorder in Finland (Project DyAdd) compares adults (n = 119, 18-55 years) with dyslexia, attention-deficit/hyperactivity disorder (ADHD), dyslexia together with ADHD (comorbid), and healthy controls with neuropsychological, psychophysical, and biological methods. The focus of this article is on the…
Kanchanatawan, Buranee; Thika, Supaksorn; Anderson, George; Galecki, Piotr; Maes, Michael
The aim of this study was to assess the neurocognitive correlates of affective symptoms in schizophrenia. Towards this end, 40 healthy controls and 80 schizophrenia patients were investigated with six tests of the Cambridge Neuropsychological Test Automated Battery (CANTAB), assessing spatial working memory, paired-association learning, one touch stocking, rapid visual information (RVP), emotional recognition test and intra/extradimensional set shifting. The Hamilton Depression (HDRS) and Anxiety (HAMA) Rating Scales and the Calgary Depression Scale for Schizophrenia (CDSS) as well as the Positive and Negative Syndrome Scale (PANSS) were also used. There were highly significant associations between all 6 CANTAB tests and HDRS, HAMA and CDSS (except RVP) scores. The most significant items associating with neurocognitive impairments in schizophrenia were self-depreciation (CDSS), fatigue, psychomotor retardation and agitation, psychic and somatic anxiety (HDRS), fears, cognitive symptoms, somatic-muscular, genito-urinary and autonomic symptoms and anxious behavior (HAMA). The selected HDRS and HAMA symptoms indicate fatigue, fears, anxiety, agitation, retardation, somatization and subjective cognitive complaints (SCC) and are therefore labeled "FAARS". Up to 28.8% of the variance in the 6 CANTAB measurements was explained by FAARS, which are better predictors of neurocognitive impairments than the PANSS negative subscale score. Neurocognitive deficits in schizophrenia are best predicted by FAARS combined with difficulties in abstract thinking. In conclusion, depression and anxiety symptoms accompanying the negative and positive symptoms of schizophrenia are associated with neurocognitive deficits indicating disorders in executive functions, attention, visual memory, and social cognition. Neurocognitive deficits in schizophrenia reflect difficulties in abstract thinking and FAARS, including subjective cognitive complaints. Copyright © 2017 Elsevier Inc. All rights
Full Text Available Autism spectrum disorder (ASD and attention deficit hyperactivity disorder (ADHD are neurodevelopmental disorders characterized by social impairments. The first objective of this study was to analyze social cognition deficits of children with ADHD, high-functioning ASD (HFASD, and typical development (TD in their performance on explicit and applied measures of theory of mind (ToM. The second objective was to investigate the relationships between executive functions and social cognition in HFASD and ADHD. One hundred and twenty-six 7- to 11-year old children, 52 with HFASD, 35 with ADHD, and 39 with TD, performed the NEPSY-II social perception subtests. Parents estimated their children's ToM skills using the Theory of Mind Inventory (ToMI. Teacher-reported data from the Behavior Rating Inventory of Executive Function (BRIEF were also obtained. The HFASD and ADHD groups showed worse performance on the verbal ToM task than the TD group, and only the performance of the HFASD group was significantly lower than the TD group on the contextual ToM task. Parents also estimated that the HFASD group had more difficulties on the applied ToM than the ADHD and TD groups. Furthermore, there is a different executive function-theory of mind link in the HFASD and ADHD groups: behavioral regulation processes such as inhibition and emotional control are more associated with social cognition in children with ADHD, whereas metacognitive processes such as initiation and planning have a strong association with social cognition in children with HFASD. These findings have implications for understanding social perception deficits in neurodevelopmental disorders, highlighting the need for early intervention.
Amy Claire Reichelt
Full Text Available Adolescence poses as both a transitional period in neurodevelopment and lifestyle practices. In particular, the developmental trajectory of the prefrontal cortex, a critical region for behavioural control and self-regulation, is enduring, not reaching functional maturity until the early 20s in humans. Furthermore, the neurotransmitter dopamine is particularly abundant during adolescence, tuning the brain to rapidly learn about rewards and regulating aspects of neuroplasticity. Thus, adolescence is proposed to represent a period of vulnerability towards reward-driven behaviours such as the consumption of palatable high fat and high sugar diets. This is reflected in the increasing prevalence of obesity in children and adolescents as they are the greatest consumers of junk foods. Excessive consumption of diets laden in saturated fat and refined sugars not only leads to weight gain and the development of obesity, but experimental studies with rodents indicate they evoke cognitive deficits in learning and memory process by disrupting neuroplasticity and altering reward processing neurocircuitry. Consumption of these high fat and high sugar diets have been reported to have a particularly pronounced impact on cognition when consumed during adolescence, demonstrating a susceptibility of the adolescent brain to enduring cognitive deficits. The adolescent brain, with heightened reward sensitivity and diminished behavioural control compared to the mature adult brain, appears to be a risk for aberrant eating behaviours that may underpin the development of obesity. This review explores the neurodevelopmental changes in the prefrontal cortex and mesocortical dopamine signalling that occur during adolescence, and how these potentially underpin the overconsumption of palatable food and development of obesogenic diet induced cognitive deficits.
Full Text Available Abstract Background Atypical antipsychotics provide better control of the negative and affective symptoms of schizophrenia when compared with conventional neuroleptics; nevertheless, their heightened ability to improve cognitive dysfunction remains a matter of debate. This study aimed to examine the changes in cognition associated with long-term antipsychotic treatment and to evaluate the effect of the type of antipsychotic (conventional versus novel antipsychotic drugs on cognitive performance over time. Methods In this naturalistic study, we used a comprehensive neuropsychological battery of tests to assess a sample of schizophrenia patients taking either conventional (n = 13 or novel antipsychotics (n = 26 at baseline and at two years after. Results Continuous antipsychotic treatment regardless of class was associated with improvement on verbal fluency, executive functions, and visual and verbal memory. Patients taking atypical antipsychotics did not show greater cognitive enhancement over two years than patients taking conventional antipsychotics. Conclusions Although long-term antipsychotic treatment slightly improved cognitive function, the switch from conventional to atypical antipsychotic treatment should not be based exclusively on the presence of these cognitive deficits.
Full Text Available Mandy H Chan,1 Patrick WL Leung,2 Ting-pong Ho,3 Se-fong Hung,4 Chi-chiu Lee,5 Chun-pan Tang,5 Ka-chai Cheung,2 Fung-yee Ching,2 Fefe HK Chan,6 Lu-hua Chen,2 Merce Garcia-Barcelo,7 Pak-chung Sham3 1Department of Clinical Psychology, Kowloon Hospital, Hospital Authority, 2Department of Psychology, The Chinese University of Hong Kong, 3Department of Psychiatry, University of Hong Kong, 4Department of Psychiatry, The Chinese University of Hong Kong, 5Department of Psychiatry, Kwai Chung Hospital, Hospital Authority, 6Department of Clinical Psychology, Alice Ho Mui Ling Nethersole Hospital, Hospital Authority, 7Department of Surgery, University of Hong Kong, Hong Kong, People’s Republic of China Background: Methylphenidate (MPH has been found to be an effective medication for attention-deficit/hyperactivity disorder (ADHD. However, there are neither consistent nor sufficient findings on whether psychiatric comorbidities and associated cognitive functions of ADHD are related to treatment response to MPH in ADHD children.Objectives: This study investigated whether psychiatric comorbidities, IQ, and neurocognitive deficits are related to treatment response to MPH in ADHD children. In some ways, it is preferable to have a drug that the effectiveness of which to a disorder is not affected by its associated cognitive functions and psychiatric comorbidities. On the other hand, it is likely that the baseline symptom severity of ADHD is associated with the effectiveness of MPH treatment on the symptoms post treatment.Methods: A total of 149 Chinese boys (aged 6–12 years with ADHD, combined type, and normal IQ participated in this study. Assessment of ADHD symptom severity was conducted pre and post MPH treatment, while assessment of psychiatric comorbidities, IQ, and neurocognitive deficits was performed in a non-medicated condition. Treatment response was defined as the ADHD symptom severity post MPH treatment.Results: Results indicated that MPH
Zhang, Qin; Yang, Chen; Liu, Tianyao; Liu, Liang; Li, Fen; Cai, Yulong; Lv, Keyi; Li, Xin; Gao, Junwei; Sun, Dayu; Xu, Haiwei; Yang, Qingwu; Fan, Xiaotang
Alzheimer's disease (AD) is the most common cause of dementia. In addition to cognitive impairments, deficits in non-cognitive behaviors are also common neurological sequelae in AD. Here, we show that complex behavioral deficits in 7-month-old APPswe/PSEN1dE9 (APP/PS1) mice include impairments in object recognition, deficient social interaction, increased depression and buried marbles. Citalopram, one of the selective serotonin reuptake inhibitors (SSRIs), ameliorated the amyloid deposition in AD patients and transgenic animal models. After treatment for 4 weeks, citalopram rescued the deficits in short-term memory, sociability and depression in these mice. Further immunohistochemical analysis showed chronic citalopram treatment significantly attenuated β-amyloid deposition and microglial activation in the brains of APP/PS1 mice as demonstrated previously. Parvalbumin (PV) interneurons, which are the primary cellular subtype of GABAergic neurons and considered indispensable for short-term memory and social interaction, also contributed to the progress of depression. Additionally, we found the citalopram could significantly increase the PV-positive neurons in the cortex of APP/PS1 mice without alteration in the hippocampus, which might contribute to the improvement of behavioral performance. Our findings suggest that citalopram might be a potential candidate for the early treatment of AD. Copyright © 2017 Elsevier Ltd. All rights reserved.
Muccigrosso, Megan M; Ford, Joni; Benner, Brooke; Moussa, Daniel; Burnsides, Christopher; Fenn, Ashley M; Popovich, Phillip G; Lifshitz, Jonathan; Walker, Fredrick Rohan; Eiferman, Daniel S; Godbout, Jonathan P
Traumatic brain injury (TBI) elicits immediate neuroinflammatory events that contribute to acute cognitive, motor, and affective disturbance. Despite resolution of these acute complications, significant neuropsychiatric and cognitive issues can develop and progress after TBI. We and others have provided novel evidence that these complications are potentiated by repeated injuries, immune challenges and stressors. A key component to this may be increased sensitization or priming of glia after TBI. Therefore, our objectives were to determine the degree to which cognitive deterioration occurred after diffuse TBI (moderate midline fluid percussion injury) and ascertain if glial reactivity induced by an acute immune challenge potentiated cognitive decline 30 days post injury (dpi). In post-recovery assessments, hippocampal-dependent learning and memory recall were normal 7 dpi, but anterograde learning was impaired by 30 dpi. Examination of mRNA and morphological profiles of glia 30 dpi indicated a low but persistent level of inflammation with elevated expression of GFAP and IL-1β in astrocytes and MHCII and IL-1β in microglia. Moreover, an acute immune challenge 30 dpi robustly interrupted memory consolidation specifically in TBI mice. These deficits were associated with exaggerated microglia-mediated inflammation with amplified (IL-1β, CCL2, TNFα) and prolonged (TNFα) cytokine/chemokine expression, and a marked reactive morphological profile of microglia in the CA3 of the hippocampus. Collectively, these data indicate that microglia remain sensitized 30 dpi after moderate TBI and a secondary inflammatory challenge elicits robust microglial reactivity that augments cognitive decline. Traumatic brain injury (TBI) is a major risk factor in development of neuropsychiatric problems long after injury, negatively affecting quality of life. Mounting evidence indicates that inflammatory processes worsen with time after a brain injury and are likely mediated by glia. Here
Sharif, Farkhondeh; Zarei, Shekufe; Alavi Shooshtari, Ali; Vossoughi, Mehrdad
Attention deficit hyperactivity disorder is one of the most common psychiatric disorders in children. The study aimed to evaluate the effectiveness of stress management program using cognitive behavior approach on mental health of the mothers of the children with attention deficit hyperactivity disorder. In this interventional study, 90 mothers of the children with attention deficit hyperactivity disorder were randomly allocated into three intervention, placebo, and control groups. The general health questionnaire was used to measure mental health. Besides, stress was assessed through the depression-anxiety-stress scale. The two instruments were completed at baseline, immediately after, and one month after the intervention by the mothers. Afterwards, within group comparisons were made using one-sample repeated measurement ANOVA. One-way ANOVA was used for inter group comparisons. Mothers in the placebo group only participated in meetings to talk and express feelings without receiving any interventions. At the baseline, no significant difference was found among the three groups regarding the means of stress, anxiety, depression, and mental health. However, a significant difference was observed in the mean score of stress immediately after the intervention (P = 0.033). The results also showed a significant difference among the three groups regarding the mean score of mental health (P mental health score remained significant only in the intervention group (P mental health of the mothers of the children with attention deficit hyperactivity disorder.
... Program Manager, USDA, Forest Service, Office of Safety and Occupational and Health, 1400 Independence... Management Handbook (FSH) 6209.11. This system is abolished and removed from the inventory of the USDA System... DEPARTMENT OF AGRICULTURE Office of the Secretary Abolishment of Privacy Act System of Records...
Tsai, C-L; Pan, C-Y; Cherng, R-J; Wu, S-K
The purpose of this study was to investigate whether children with developmental co-ordination disorder and balance problem (DCD-BP) had greater problems than controls in performing a primary balance task while concurrently completing different cognitive tasks varying in oral or listening cognitive complexity, as well as to investigate the automatization deficit hypothesis of DCD-BP. Children with DCD-BP (n= 39), along with age-matched control counterparts (n= 39), were placed on automatic processing situation under dual-task conditions. All children were required to perform a primary task, five dual-task paradigms (oral counting task, auditory-verbal reaction task, auditory-choice reaction task, auditory-memory task and articulation alone) and an eyes-closed balancing task. In the primary task condition, the differences were not statistically significant (P= 0.393) between children with and without DCD-BP. However, children with DCD-BP were significantly more impaired on three of five dual-task conditions (oral counting task: P= 0.003; auditory-verbal reaction task: P= 0.011; auditory-memory task: P= 0.041) compared with the single-task situation, with the exception of the auditory-choice reaction task (P= 0.471) and articulation alone (P= 0.067). These results suggest that children with DCD-BP were more cognitively dependant and may have an automatization deficit.
Yang, Rongwang; Gao, Weijia; Li, Rong; Zhao, Zhengyan
With early initiation of thyroxine supplementation, children with congenital hypothyroidism (CH) retain some subtle deficits, such as attention and inhibitory control problems. This study assessed the effects of atomoxetine on cognitive functions in treatment of attention deficit hyperactivity disorder (ADHD) symptoms in children with CH. In a 6-month, open-labeled pilot study, 12 children were recruited and received atomoxetine. The measures of efficacy were scores on the Swanson, Nolan and Pelham Teacher and Parent Rating Scale, version IV (SNAP-IV) and Clinical Global Impression-Severity scale (CGI-S). The cognitive functions were evaluated with the Wechsler Intelligence Scale for Chinese Children, Digit Span, Wisconsin Card Sorting Test, and Stroop test. A statistically significant difference was found between the mean CGI-S and SNAP-IV scores before and after treatment (p Atomoxetine appears to be useful in improving ADHD symptoms, as well as cognitive functions, in children with CH. Larger, randomized, double-blinded, clinical trials are required to replicate these results. © The Author 2015. Published by Oxford University Press on behalf of CINP.
Conclusions: oAβ-accelerated neuronal senescence may be associated with the cognitive impairment in 5XFAD mice. Senescence-associated marker p16 can serve as an indicator to estimate the cognitive prognosis for AD population.
Bazika, D.A.; Loganovs'kij, K.M.; Yil'jenko, Yi.M.; Chumak, S.A.; Bomko, M.O.
The possible effects of low dose ionizing radiation on human cognitive function in adult hood and in utero was estimated. Cognitive tests, telomere length and expression of genes regulating telomere function were studied in Chornobyl cleanup workers who were exposed to doses under 500 mSv (n = 326) and subjects exposed in utero during the first days after the accident Prypiat town (n = 104). The neuro cognitive assessment covered memory, attention, language, executive and visiospatial functions. In young adults after prenatal exposure a relation ship was analyzed between a cognitive function and radiation dose to foetus, brain and thyroid gland. Internal controls were used for both groups - the group of Chornobyl cleanup workers exposed in doses less than 20 mSv and an age- matched comparison group from radioactively contaminated areas for subjects exposed in utero . This study shows that cognitive deficit in humans at a late period after radiation exposure is influenced by dose, age at exposure and gene regulation of telomere function
Fossati, Andrea; Somma, Antonella; Krueger, Robert F; Markon, Kristian E; Borroni, Serena
This study aims at testing the hypothesis that the Diagnostic and Statistical Manual of Mental Disorders fifth edition (DSM-5) alternative model of personality disorder (AMPD) traits may be significantly associated with deficits on 2 different social cognition tasks, namely, the Reading the Mind in the Eyes Test and the Movie for the Assessment of Social Cognition, in a sample of consecutively admitted inpatients and outpatients. The sample was composed of 181 consecutively admitted participants (57.5% women; mean age = 38.58 years). Correlation coefficients and partial correlation coefficients were computed in order to assess the associations among social cognition tasks, DSM-5 AMPD traits, and dimensionally assessed DSM-5 Section II personality disorders. Specific maladaptive traits listed in the DSM-5 AMPD were significantly associated with Reading the Mind in the Eyes Test scores and Movie for the Assessment of Social Cognition scores, even when the effect of selected DSM-5 Section II personality disorders was controlled for. Our results support the relevance of studying social cognitive functioning in subjects suffering from personality disorders. Copyright © 2017 John Wiley & Sons, Ltd.
Reimers, Tonny Solveig; Mortensen, Erik Lykke; Schmiegelow, Kjeld
To analyze the impact of potential predictors on memory performance in survivors of childhood brain tumors and to examine whether deficits in memory after radiotherapy (RT) should be considered part of a more global mental dysfunction.......To analyze the impact of potential predictors on memory performance in survivors of childhood brain tumors and to examine whether deficits in memory after radiotherapy (RT) should be considered part of a more global mental dysfunction....
Hanlon, Lauren A.; Huh, Jimmy W.
Elevated microglial/macrophage-associated biomarkers in the cerebrospinal fluid of infant victims of abusive head trauma (AHT) suggest that these cells play a role in the pathophysiology of the injury. In a model of AHT in 11-day-old rats, 3 impacts (24 hours apart) resulted in spatial learning and memory deficits and increased brain microglial/macrophage reactivity, traumatic axonal injury, neuronal degeneration, and cortical and white-matter atrophy. The antibiotic minocycline has been effective in decreasing injury-induced microglial/macrophage activation while simultaneously attenuating cellular and functional deficits in models of neonatal hypoxic ischemia, but the potential for this compound to rescue deficits after impact-based trauma to the immature brain remains unexplored. Acute minocycline administration in this model of AHT decreased microglial/macrophage reactivity in the corpus callosum of brain-injured animals at 3 days postinjury, but this effect was lost by 7 days postinjury. Additionally, minocycline treatment had no effect on traumatic axonal injury, neurodegeneration, tissue atrophy, or spatial learning deficits. Interestingly, minocycline-treated animals demonstrated exacerbated injury-induced spatial memory deficits. These results contrast with previous findings in other models of brain injury and suggest that minocycline is ineffective in reducing microglial/macrophage activation and ameliorating injury-induced deficits following repetitive neonatal traumatic brain injury. PMID:26825312
Jacobsen, J P R; Redrobe, J P; Hansen, H H
performed equally well in passive avoidance, object recognition and the Morris water maze. Thus, some aspects of working/short-term memory are disrupted in T/T mice. Using in situ hybridization, we further found the cognitive deficits in T/T mice to be paralleled by reduced brain-derived neurotrophic factor...... the brain following doxycycline treatment. We tested T/T and wild type (WT) littermate mice in five distinct learning and memory paradigms. In Y-maze spontaneous alternations and five-trial inhibitory avoidance the performance of T/T mice was markedly inferior to WT mice. In contrast, T/T and WT mice...
Bora, E; Binnur Akdede, B; Alptekin, K
Most studies suggested that patients with deficit schizophrenia have more severe impairment compared with patients with non-deficit schizophrenia. However, it is not clear whether deficit and non-deficit schizophrenia are associated with differential neurocognitive profiles. The aim of this meta-analytic review was to compare cognitive performances of deficit and non-deficit patients with each other and with healthy controls. In the current meta-analysis, differences in cognitive abilities between 897 deficit and 1636 non-deficit patients with schizophrenia were examined. Cognitive performances of 899 healthy controls were also compared with 350 patients with deficit and 592 non-deficit schizophrenia. Both deficit (d = 1.04-1.53) and non-deficit (d = 0.68-1.19) schizophrenia were associated with significant deficits in all cognitive domains. Deficit patients underperformed non-deficit patients in all cognitive domains (d = 0.24-0.84) and individual tasks (d = 0.39-0.93). The relationship between deficit syndrome and impairment in olfaction, social cognition, verbal fluency, and speed-based cognitive tasks were relatively stronger. Our findings suggest that there is consistent evidence for a significant relationship between deficit syndrome and more severe cognitive impairment in schizophrenia.
Mokhtari-Zaer, Amin; Ghodrati-Jaldbakhan, Shahrbanoo; Vafaei, Abbas Ali; Miladi-Gorji, Hossein; Akhavan, Maziar M; Bandegi, Ahmad Reza; Rashidy-Pour, Ali
Chronic exposure to morphine results in cognitive deficits and alterations of apoptotic proteins in favor of cell death in the hippocampus, a brain region critically involved in learning and memory. Physical activity has been shown to have beneficial effects on brain health. In the current work, we examined the effects of voluntary and treadmill exercise on spontaneous withdrawal signs, the associated cognitive defects, and changes of apoptotic proteins in morphine-dependent rats. Morphine dependence was induced through bi-daily administrations of morphine (10mg/kg) for 10 days. Then, the rats were trained under two different exercise protocols: mild treadmill exercise or voluntary wheel exercise for 10 days. After exercise training, their spatial learning and memory and aversive memory were examined by a water maze and by an inhibitory avoidance task, respectively. The expression of the pro-apoptotic protein Bax and the anti-apoptotic protein Bcl-2 in the hippocampus were determined by immunoblotting. We found that chronic exposure to morphine impaired spatial and aversive memory and remarkably suppressed the expression of Bcl-2, but Bax expression remained constant. Both voluntary and treadmill exercise alleviated memory impairment, increased the expression of Bcl-2 protein, and only the later suppressed the expression of Bax protein in morphine-dependent animals. Moreover, both exercise protocols diminished the occurrence of spontaneous morphine withdrawal signs. Our findings showed that exercise reduces the spontaneous morphine-withdrawal signs, blocks the associated impairment of cognitive performance, and overcomes morphine-induced alterations in apoptotic proteins in favor of cell death. Thus, exercise may be a useful therapeutic strategy for cognitive and behavioral deficits in addict individuals. Copyright © 2014 Elsevier B.V. All rights reserved.
Full Text Available Carbon ion therapy is a promising modality in radiotherapy to treat tumors, however, a potential risk of induction of late normal tissue damage should still be investigated and protected. The aim of the present study was to explore the long-term cognitive deficits provoked by a high-linear energy transfer (high-LET carbon ions in mice by targeting to hippocampus which plays a crucial role in memory and learning. Our data showed that, one month after 4 Gy carbon ion exposure, carbon ion irradiation conspicuously resulted in the impaired cognitive performance, neurodegeneration and neuronal cell death, as well as the reduced mitochondrial integrity, the disrupted activities of tricarboxylic acid cycle flux and electron transport chain, and the depressed antioxidant defense system, consequently leading to a decline of ATP production and persistent oxidative damage in the hippocampus region. Mechanistically, we demonstrated the disruptions of mitochondrial homeostasis and redox balance typically characterized by the disordered mitochondrial dynamics, mitophagy and glutathione redox couple, which is closely associated with the inhibitions of PINK1 and NRF2 signaling pathway as the key regulators of molecular responses in the context of neurotoxicity and neurodegenerative disorders. Most importantly, we found that administration with melatonin as a mitochondria-targeted antioxidant promoted the PINK1 accumulation on the mitochondrial membrane, and augmented the NRF2 accumulation and translocation. Moreover, melatonin pronouncedly enhanced the molecular interplay between NRF2 and PINK1. Furthermore, in the mouse hippocampal neuronal cells, overexpression of NRF2/PINK1 strikingly protected the hippocampal neurons from carbon ion-elicited toxic insults. Thus, these data suggest that alleviation of the sustained mitochondrial dysfunction and oxidative stress through co-modulation of NRF2 and PINK1 may be in charge of restoration of the cognitive
Lee, Bombi; Shim, Insop; Lee, Hyejung; Hahm, Dae-Hyun
Post-traumatic stress disorder (PTSD) is a condition that develops after an individual has experienced a major trauma. This psychopathological response to traumatic stressors induces learning and memory deficits in rats. Oleuropein (OLE), a major compound in olive leaves, has been reported to possess several pharmacological properties, including anti-cancer, anti-diabetic, anti-atherosclerotic and neuroprotective activities. However, the cognitive effects of OLE and its mechanism of action have remained unclear in PTSD. In this study, we examined whether OLE improved spatial cognitive impairment induced in rats following single prolonged stress (SPS), an animal model of PTSD. Male rats were treated intraperitoneally (i.p.) with vehicle or various doses of OLE for 14 consecutive days after the SPS procedure. The SPS procedure resulted in cognitive impairment in the object recognition task and the Morris water maze test, which was reversed by OLE (100 mg/kg, i.p). Additionally, as assessed by immunohistochemistry and reverse transcription-polymerase chain reaction analysis, the administration of OLE significantly alleviated memory-associated decreases in the levels of brain-derived neurotrophic factor and cAMP response element-binding protein and mRNA in the hippocampus. Together, these findings suggest that OLE attenuated SPS-induced cognitive impairment significantly by inhibiting the expression of pro-inflammatory mediators in the rat brain. Thus, OLE reversed several behavioral impairments triggered by the traumatic stress of SPS and might be a potential useful therapeutic intervention for PTSD.
Full Text Available BACKGROUND: The association between brain white matter lesions and cognitive impairment in old age is well established. However, little is known about this association in midlife. As this information will inform policy for early preventative healthcare initiatives, we investigated non-periventricular frontal, temporal, parietal and occipital lobe white matter hyperintensities (WMH in relation to cognitive function in 428 (232 women community-dwelling adults aged 44 to 48 years. RESULTS: Frontal white matter lesions were significantly associated with greater intraindividual RT variability in women, while temporal WMH were associated with face recognition deficits in men. Parietal and occipital lobe lesions were unrelated to cognitive performance. These findings did not differ when education and a range of health variables, including vascular risk factors, were taken into account. CONCLUSION: Gender differences in WMH-cognition associations are discussed, and we conclude that small vessel disease is present in midlife and has functional consequences which are generally not recognized. Preventative strategies should, therefore, begin early in life.
Chen, D C; Du, X D; Yin, G Z; Yang, K B; Nie, Y; Wang, N; Li, Y L; Xiu, M H; He, S C; Yang, F D; Cho, R Y; Kosten, T R; Soares, J C; Zhao, J P; Zhang, X Y
Schizophrenia patients have a higher prevalence of type 2 diabetes mellitus with impaired glucose tolerance (IGT) than normals. We examined the relationship between IGT and clinical phenotypes or cognitive deficits in first-episode, drug-naïve (FEDN) Han Chinese patients with schizophrenia. A total of 175 in-patients were compared with 31 healthy controls on anthropometric measures and fasting plasma levels of glucose, insulin and lipids. They were also compared using a 75 g oral glucose tolerance test and the homeostasis model assessment of insulin resistance (HOMA-IR). Neurocognitive functioning was assessed using the MATRICS Consensus Cognitive Battery (MCCB). Patient psychopathology was assessed using the Positive and Negative Syndrome Scale (PANSS). Of the patients, 24.5% had IGT compared with none of the controls, and they also had significantly higher levels of fasting blood glucose and 2-h glucose after an oral glucose load, and were more insulin resistant. Compared with those patients with normal glucose tolerance, the IGT patients were older, had a later age of onset, higher waist or hip circumference and body mass index, higher levels of low-density lipoprotein and triglycerides and higher insulin resistance. Furthermore, IGT patients had higher PANSS total and negative symptom subscale scores, but no greater cognitive impairment except on the emotional intelligence index of the MCCB. IGT occurs with greater frequency in FEDN schizophrenia, and shows association with demographic and anthropometric parameters, as well as with clinical symptoms but minimally with cognitive impairment during the early course of the disorder.
Iglesias-Sarmiento, Valentín; Deaño, Manuel; Alfonso, Sonia; Conde, Ángeles
The purpose of this study was to examine the contribution of cognitive functioning to arithmetic problem solving and to explore the cognitive profiles of children with attention deficit and/or hyperactivity disorder (ADHD) and with mathematical learning disabilities (MLD). The sample was made up of a total of 90 students of 4th, 5th, and 6th grade organized in three: ADHD (n=30), MLD (n=30) and typically achieving control (TA; n=30) group. Assessment was conducted in two sessions in which the PASS processes and arithmetic problem solving were evaluated. The ADHD group's performance in planning and attention was worse than that of the control group. Children with MLD obtained poorer results than the control group in planning and simultaneous and successive processing. Executive processes predicted arithmetic problem solving in the ADHD group whereas simultaneous processing was the unique predictor in the MLD sample. Children with ADHD and with MLD showed characteristic cognitive profiles. Groups' problem-solving performance can be predicted from their cognitive functioning. Copyright © 2016 Elsevier Ltd. All rights reserved.
Effects of a program of cognitive-behavioural group therapy, vestibular rehabilitation, and psychoeducational explanations on patients with dizziness and no quantified balance deficit, compared to patients with dizziness and a quantified balance deficit.
Schmid, D A; Allum, J H J; Sleptsova, M; Gross, S; Gaab, J; Welge-Lüssen, A; Schaefert, R; Langewitz, W
We examined whether a program combining cognitive-behavioural therapy (CBT), vestibular rehabilitation (VR) and psychoeducation is equally effective in improving psychometric measures in patients with dizziness independent of a balance deficit. Measures of patients with dizziness only (DO) were compared to those of patients also having a quantified balance deficit (QBD). 32 patients (23 female, 9 male) with persistent dizziness were analysed as 2 groups based on stance and gait balance control: those with QBD (pathological balance) or DO (normal balance). Dizziness Handicap Inventory (DHI) and Brief Symptom Inventory (BSI) questionnaires were used pre- and post-therapy to assess psychometric measures. Patients then received the same combination therapy in a group setting. The QBD group mean age was 60.6, SD 8.3, and DO group mean age 44.8, SD 12.1, years. Pre-therapy, questionnaire scores were pathological but not different between groups. Balance improved significantly for the QBD group (p=0.003) but not for the DO group. DHI and BSI scores improved significantly in the DO group (0.001balance control improving to near normal. Possibly, greater focus on phobic anxiety during the group therapy program would have improved psychological measures of QBD patient. Copyright © 2017 Elsevier Inc. All rights reserved.
Lysaker, Paul H; Erikson, Molly; Macapagal, Kathryn R; Tunze, Chloe; Gilmore, Emily; Ringer, Jamie M
Although negative symptoms are a barrier to recovery from schizophrenia, little is understood about the psychological processes that reinforce and sustain them. To explore this issue, this study used structural equation modeling to test whether the impact of social withdrawal and emotion recognition deficits upon negative symptoms is mediated by the richness or poverty of personal narratives. The participants were 99 adults with schizophrenia spectrum disorders. Social cognition was assessed using the Bell-Lysaker Emotional Recognition Task; social withdrawal, using the Quality of Life Scale; narrative coherence, using the Scale To Assess Narrative Development; and negative symptoms, using the Positive and Negative Syndrome Scale. The findings reveal that although social cognition deficits and social withdrawal are significantly associated with negative symptom severity, these relationships become nonsignificant when personal narrative integrity is examined as a mediating factor. These results indicate that the development of personal narratives may be directly linked to the severity of negative symptoms; this construct may be a useful target for future interventions.
Phelps, Thomas I; Bondi, Corina O; Ahmed, Rashid H; Olugbade, Yewande T; Kline, Anthony E
Antipsychotic drugs (APDs) are provided in the clinic to manage traumatic brain injury (TBI)-induced agitation and aggression. Experimental TBI studies consistently show that daily administration of the APDs, haloperidol (HAL) and risperidone (RISP), hinder recovery. However, it is unknown how long the adverse effects remain after cessation of treatment. To elucidate this clinically relevant issue, anesthetized male rats were randomly assigned to four TBI (controlled cortical impact) and four sham groups administered HAL (0.5 mg/kg), RISP (0.45 mg/kg), bromocriptine (BRO; 5.0 mg/kg, included as a control for D2 receptor action), or vehicle (VEH; 1 mL/kg) 24 h after surgery and once-daily for 19 days. Motor and cognitive recovery was assessed on days 1-5 and 14-19, respectively, and again at 1 and 3 months after drug withdrawal. No overall group differences were observed for motor function among the TBI groups, although the HAL group showed a greater beam-walk deficit on day 5 versus the VEH and BRO groups. Cognitive recovery was significantly impaired in the HAL and RISP groups during the treatment phase versus VEH and BRO. Further, BRO was superior to VEH (p=0.0042). At 1 month, both groups that received APDs continued to exhibit significant cognitive impairment versus VEH and BRO; at 3 months, only the HAL group was impaired. Moreover, the HAL, RISP, and VEH groups continued to be cognitively deficient versus BRO, which also reduced cortical damage. These data replicate previous reports that HAL and RISP impede cognitive recovery after TBI and expand the literature by revealing that the deleterious effects persist for 3 months after drug discontinuation. BRO conferred cognitive benefits when administered concomitantly with behavioral testing, thus replicating previous findings, and also after cessation demonstrating enduring efficacy.
Virginia de Oliveira Rosa
Full Text Available Abstract Background Cognitive training has received increasing attention as a non-pharmacological approach for the treatment of attention deficit/hyperactivity disorder (ADHD in children and adolescents. Few studies have assessed cognitive training as add-on treatment to medication in randomized placebo controlled trials. The purpose of this preliminary study was to explore the feasibility of implementing a computerized cognitive training program for ADHD in our environment, describe its main characteristics and potential efficacy in a small pilot study. Methods Six ADHD patients aged 10-12-years old receiving stimulants and presenting residual symptoms were enrolled in a randomized clinical trial to either a standard cognitive training program or a controlled placebo condition for 12 weeks. The primary outcome was core ADHD symptoms measured using the Swanson, Nolan and Pelham Questionnaire (SNAP-IV scale. Results We faced higher resistance than expected to patient enrollment due to logistic issues to attend face-to-face sessions in the hospital and to fill the requirement of medication status and absence of some comorbidities. Both groups showed decrease in parent reported ADHD symptoms without statistical difference between them. In addition, improvements on neuropsychological tests were observed in both groups – mainly on trained tasks. Conclusions This protocol revealed the need for new strategies to better assess the effectiveness of cognitive training such as the need to implement the intervention in a school environment to have an assessment with more external validity. Given the small sample size of this pilot study, definitive conclusions on the effects of cognitive training as add-on treatment to stimulants would be premature.
Rosa, Virginia de Oliveira; Schmitz, Marcelo; Moreira-Maia, Carlos Roberto; Wagner, Flavia; Londero, Igor; Bassotto, Caroline de Fraga; Moritz, Guilherme; de Souza, Caroline Dos Santos; Rohde, Luis Augusto Paim
Cognitive training has received increasing attention as a non-pharmacological approach for the treatment of attention deficit/hyperactivity disorder (ADHD) in children and adolescents. Few studies have assessed cognitive training as add-on treatment to medication in randomized placebo controlled trials. The purpose of this preliminary study was to explore the feasibility of implementing a computerized cognitive training program for ADHD in our environment, describe its main characteristics and potential efficacy in a small pilot study. Six ADHD patients aged 10-12-years old receiving stimulants and presenting residual symptoms were enrolled in a randomized clinical trial to either a standard cognitive training program or a controlled placebo condition for 12 weeks. The primary outcome was core ADHD symptoms measured using the Swanson, Nolan and Pelham Questionnaire (SNAP-IV scale). We faced higher resistance than expected to patient enrollment due to logistic issues to attend face-to-face sessions in the hospital and to fill the requirement of medication status and absence of some comorbidities. Both groups showed decrease in parent reported ADHD symptoms without statistical difference between them. In addition, improvements on neuropsychological tests were observed in both groups - mainly on trained tasks. This protocol revealed the need for new strategies to better assess the effectiveness of cognitive training such as the need to implement the intervention in a school environment to have an assessment with more external validity. Given the small sample size of this pilot study, definitive conclusions on the effects of cognitive training as add-on treatment to stimulants would be premature.
Merker, Sören; Reif, Andreas; Ziegler, Georg C; Weber, Heike; Mayer, Ute; Ehlis, Ann-Christine; Conzelmann, Annette; Johansson, Stefan; Müller-Reible, Clemens; Nanda, Indrajit; Haaf, Thomas; Ullmann, Reinhard; Romanos, Marcel; Fallgatter, Andreas J; Pauli, Paul; Strekalova, Tatyana; Jansch, Charline; Vasquez, Alejandro Arias; Haavik, Jan; Ribasés, Marta; Ramos-Quiroga, Josep Antoni; Buitelaar, Jan K; Franke, Barbara; Lesch, Klaus-Peter
Attention-deficit/hyperactivity disorder (ADHD) is a common, highly heritable neurodevelopmental disorder with profound cognitive, behavioral, and psychosocial impairments with persistence across the life cycle. Our initial genome-wide screening approach for copy number variants (CNVs) in ADHD implicated a duplication of SLC2A3, encoding glucose transporter-3 (GLUT3). GLUT3 plays a critical role in cerebral glucose metabolism, providing energy for the activity of neurons, which, in turn, moderates the excitatory-inhibitory balance impacting both brain development and activity-dependent neural plasticity. We therefore aimed to provide additional genetic and functional evidence for GLUT3 dysfunction in ADHD. Case-control association analyses of SLC2A3 single-nucleotide polymorphisms (SNPs) and CNVs were conducted in several European cohorts of patients with childhood and adult ADHD (SNP, n = 1,886 vs. 1,988; CNV, n = 1,692 vs. 1,721). These studies were complemented by SLC2A3 expression analyses in peripheral cells, functional EEG recordings during neurocognitive tasks, and ratings of food energy content. Meta-analysis of all cohorts detected an association of SNP rs12842 with ADHD. While CNV analysis detected a population-specific enrichment of SLC2A3 duplications only in German ADHD patients, the CNV + rs12842 haplotype influenced ADHD risk in both the German and Spanish cohorts. Duplication carriers displayed elevated SLC2A3 mRNA expression in peripheral blood cells and altered event-related potentials reflecting deficits in working memory and cognitive response control, both endophenotypic traits of ADHD, and an underestimation of energy units of high-caloric food. Taken together, our results indicate that both common and rare SLC2A3 variation impacting regulation of neuronal glucose utilization and energy homeostasis may result in neurocognitive deficits known to contribute to ADHD risk. © 2017 Association for Child and Adolescent Mental Health.
Mısır, Emre; Bora, Emre; Akdede, Berna Binnur
The primary aim of the current study was to investigate different aspects of theory of mind (ToM), including social-cognitive (ToM-reasoning) and social-perceptual (ToM-decoding) in obsessive-compulsive disorder (OCD). We also aimed to investigate the relationship between ToM, neurocognition and a number of clinical variables including overvalued ideas, schizotypal personality traits, level of insight, and disease severity. Thirty-four patients who have been diagnosed with OCD according to DSM-IV and 30 healthy controls were included in the study. All participants were given a neuropsychological battery including tasks measuring ToM-reasoning, ToM-decoding and other neurocognitive functions. Schizotypal Personality Questionnaire (SPQ), Yale Brown Obsession and Compulsion Scale (YBOC-S) and Overvalued Ideas Scale (OVIS) were also administered to the participants. Patients with OCD showed significant deficits in both aspects of ToM. ToM performances of patients showed a significant positive correlation with neurocognitive functions. When controlled for general cognition factor, patient-control difference for ToM-reasoning (F = 3,917; p = 0,05), but not ToM-decoding, remained statistically significant. ToM-reasoning impairment of patients was significantly related to the severity of OCD symptoms and poor insight (p = 0,026 and p = 0,045, respectively). On the other hand, general cognitive factor (β = 0,778; t = 3,146; p = 0,04) was found to be the only significant predictor of ToM-reasoning in OCD patients in the multiple linear regression model. OCD is associated with ToM impairment, which is related to schizotypal traits, disease severity and poor insight, yet neurocognitive deficits also significantly contribute to this finding. However, ToM-reasoning impairment could be considered as a relatively distinct feature of OCD, which is partly separate from general cognitive deficits. Copyright © 2018. Published by Elsevier Inc.
Effectiveness of Parents-Focused Cognitive-Behavioral Therapy on Attention Deficit Hyperactivity Disorder Symptoms, Obesity and Self-Esteem of Overweight Children with Attention Deficient Hyperactivity Disorder
Afsaneh Karbasi Amel
Full Text Available Background: Attention deficit hyperactivity disorder (ADHD is the most common behavioral problems that cause hyperactivity, attention deficits, academic failure, and emotional and behavioral problems in preschool and elementary school that is often hidden from the parents' eyes. The aim of this study was to determine the effectiveness of parent-based cognitive-behavioral therapy (CBT on ADHD symptoms (including attention deficit disorder, restlessness, and impulsivity, overweight and self-esteem of 6–11-year-old obese children with attention deficit hyperactivity in Isfahan. Materials and Methods: This quasi-experimental study was carried out on 40 children aged 6–11 years with ADHD and overweight or obesity (above the 85th percentile in weight for age, height, and sex diagram that their parents referred to Isfahan child and adolescent psychiatric clinic of Ali Asghar Hospital in 2015. For twenty patients, only ADHD treatment was applied, and they received no other intervention, but the others in experimental group participated in CBT sessions. Analysis tools were Coppersmith Self-Esteem Scale, ADHD conners' test, and the body mass index (BMI. Data were analyzed using analysis of variance with repeated measurements. Results: CBT by teaching parents had a significant effect on ADHD symptoms, the self-esteem of overweight and obese children with ADHD in posttest and follow-up. The results also showed that had a significant effect on ADHD symptoms, overweight and self-esteem of the obese children with ADHD (P < 0.001. Conclusions: Parents focused CBT can be considered as a complementary treatment for reducing ADHD symptoms and BMI and increased self-esteem in the obese ADHD children.
Effectiveness of Parents-Focused Cognitive-Behavioral Therapy on Attention Deficit Hyperactivity Disorder Symptoms, Obesity and Self-Esteem of Overweight Children with Attention Deficient Hyperactivity Disorder.
Karbasi Amel, Afsaneh; Karbasi Amel, Saeed; Erfan, Arefeh
Attention deficit hyperactivity disorder (ADHD) is the most common behavioral problems that cause hyperactivity, attention deficits, academic failure, and emotional and behavioral problems in preschool and elementary school that is often hidden from the parents' eyes. The aim of this study was to determine the effectiveness of parent-based cognitive-behavioral therapy (CBT) on ADHD symptoms (including attention deficit disorder, restlessness, and impulsivity), overweight and self-esteem of 6-11-year-old obese children with attention deficit hyperactivity in Isfahan. This quasi-experimental study was carried out on 40 children aged 6-11 years with ADHD and overweight or obesity (above the 85 th percentile in weight for age, height, and sex diagram) that their parents referred to Isfahan child and adolescent psychiatric clinic of Ali Asghar Hospital in 2015. For twenty patients, only ADHD treatment was applied, and they received no other intervention, but the others in experimental group participated in CBT sessions. Analysis tools were Coppersmith Self-Esteem Scale, ADHD conners' test, and the body mass index (BMI). Data were analyzed using analysis of variance with repeated measurements. CBT by teaching parents had a significant effect on ADHD symptoms, the self-esteem of overweight and obese children with ADHD in posttest and follow-up. The results also showed that had a significant effect on ADHD symptoms, overweight and self-esteem of the obese children with ADHD ( P < 0.001). Parents focused CBT can be considered as a complementary treatment for reducing ADHD symptoms and BMI and increased self-esteem in the obese ADHD children.
Dykstra, Pearl A.; Fokkema, Tineke
Data from the 1998 survey “Divorce in the Netherlands” (N = 2,223) are used to analyze differences in loneliness among divorced and married men and women. The results indicate that it makes sense to distinguish social from emotional loneliness. This is consistent with the deficit perspective, which
Dykstra, P.A.; Fokkema, C.M.
Data from the 1998 survey “Divorce in the Netherlands” (N = 2,223) are used to analyze differences in loneliness among divorced and married men and women. The results indicate that it makes sense to distinguish social from emotional loneliness. This is consistent with the deficit perspective, which
Banks, Tracy; Ninowski, Jerilyn E.; Mash, Eric J.; Semple, Deborah L.
Although attention-deficit/hyperactivity disorder (ADHD) in adults has recently emerged as an important area of research, little attention has been given to the family functioning of women with ADHD, particularly in their role as mothers. We examined parenting self-esteem, locus of control, and disciplinary styles in a community sample of mothers…
Söderlund, Göran B W; Björk, Christer; Gustafsson, Peik
Recent research has shown that acoustic white noise (80 dB) can improve task performance in people with attention deficits and/or Attention Deficit Hyperactivity Disorder (ADHD). This is attributed to the phenomenon of stochastic resonance in which a certain amount of noise can improve performance in a brain that is not working at its optimum. We compare here the effect of noise exposure with the effect of stimulant medication on cognitive task performance in ADHD. The aim of the present study was to compare the effects of auditory noise exposure with stimulant medication for ADHD children on a cognitive test battery. A group of typically developed children (TDC) took the same tests as a comparison. Twenty children with ADHD of combined or inattentive subtypes and twenty TDC matched for age and gender performed three different tests (word recall, spanboard and n-back task) during exposure to white noise (80 dB) and in a silent condition. The ADHD children were tested with and without central stimulant medication. In the spanboard- and the word recall tasks, but not in the 2-back task, white noise exposure led to significant improvements for both non-medicated and medicated ADHD children. No significant effects of medication were found on any of the three tasks. This pilot study shows that exposure to white noise resulted in a task improvement that was larger than the one with stimulant medication thus opening up the possibility of using auditory noise as an alternative, non-pharmacological treatment of cognitive ADHD symptoms.
Göran B W Söderlund
Full Text Available Background: Recent research has shown that acoustic white noise (80 dB can improve task performance in people with attention deficits and/or Attention Deficit Hyperactivity Disorder (ADHD. This is attributed to the phenomenon of stochastic resonance in which a certain amount of noise can improve performance in a brain that is not working at its optimum. We compare here the effect of noise exposure with the effect of stimulant medication on cognitive task performance in ADHD. The aim of the present study was to compare the effects of auditory noise exposure with stimulant medication for ADHD children on a cognitive test battery. A group of typically developed children (TDC took the same tests as a comparison.Methods: Twenty children with ADHD of combined or inattentive subtypes and twenty typically developed children matched for age and gender performed three different tests (word recall, spanboard and n-back task during exposure to white noise (80 dB and in a silent condition. The ADHD children were tested with and without central stimulant medication.Results: In the spanboard- and the word recall tasks, but not in the 2-back task, white noise exposure led to significant improvements for both non-medicated and medicated ADHD children. No significant effects of medication were found on any of the three tasks.Conclusion: This pilot study shows that exposure to white noise resulted in a task improvement that was larger than the one with stimulant medication thus opening up the possibility of using auditory noise as an alternative, non-pharmacological treatment of cognitive ADHD symptoms.
Xu, Pan; Wang, Kezhu; Lu, Cong; Dong, Liming; Gao, Li; Yan, Ming; Aibai, Silafu; Liu, Xinmin
Lavender essential oil (LO), an aromatic liquid extracted from Lavandula angustifolia Mill., has been traditionally used in the treatments of many nervous system diseases, and recently LO also reported to be effective for the Alzheimer's disease (AD). The improvement effect of lavender oil (LO) on the scopolamine-induced cognitive deficits in mice and H 2 O 2 induced cytotoxicity in PC12 cells have been evaluated. The relevant mechanism was also researched from the perspective of antioxidant effect and cholinergic system modulation. Cognitive deficits were induced in C57BL/6J mice treated with scopolamine (1mg/kg, i.p.) and were assessed by Morris water maze (MWM) and step-through passive avoidance tests. Then their hippocampus were removed for biochemical assays (acetylcholinesterase (AChE), superoxide dismutase (SOD), glutathione peroxidase (GPX) and malondialdehyde (MDA)). In vitro, the cytotoxicity were induced by 4h exposure to H 2 O 2 in PC12 and evaluated by cell viability (MTT), lactate dehydrogenase (LDH) level, nitric oxide (NO) release, reactive oxygen species (ROS) production and mitochondrial membrane potential (MMP). The results demonstrated that LO (100mg/kg) could improve the cognitive performance of scopolamine induced mice in behavioral tests. Meanwhile, it significantly decreased the AChE activity, MDA level, and increase SOD and GPX activities of the model. Moreover, LO (12μg/mL) protected PC12 cells from H 2 O 2 induced cytotoxicity by reducing LDH, NO release, intracellular ROS accumulation and MMP loss. It was suggested that LO could show neuroprotective effect in AD model in vivo (scopolamine-treated mice) and in vitro (H 2 O 2 induced PC12 cells) via modulating oxidative stress and AChE activity. Copyright © 2016. Published by Elsevier Ireland Ltd.
Ni, Hong; Zhao, Dong-Jing; Tian, Tian
Because the ketogenic diet (KD) was affecting expression of energy metabolism- related genes in hippocampus and because lipid membrane peroxidation and its associated autophagy stress were also found to be involved in energy depletion, we hypothesized that KD might exert its neuroprotective action via lipid membrane peroxidation and autophagic signaling. Here, we tested this hypothesis by examining the long-term expression of lipid membrane peroxidation-related cPLA2 and clusterin, its downstream autophagy marker Beclin-1, LC3 and p62, as well as its execution molecule Cathepsin-E following neonatal seizures and chronic KD treatment. On postnatal day 9 (P9), 48 Sprague-Dawley rats were randomly assigned to two groups: flurothyl-induced recurrent seizures group and control group. On P28, they were further randomly divided into the seizure group without ketogenic diet (RS+ND), seizure plus ketogenic diet (RS+KD), the control group without ketogenic diet (NS+ND), and the control plus ketogenic diet (NS+KD). Morris water maze test was performed during P37-P43. Then mossy fiber sprouting and the protein levels were detected by Timm staining and Western blot analysis, respectively. Flurothyl-induced RS+ND rats show a long-term lower amount of cPLA2 and LC3II/I, and higher amount of clusterin, Beclin-1, p62 and Cathepsin-E which are in parallel with hippocampal mossy fiber sprouting and cognitive deficits. Furthermore, chronic KD treatment (RS+KD) is effective in restoring these molecular, neuropathological and cognitive changes. The results imply that a lipid membrane peroxidation and autophagy-associated pathway is involved in the aberrant hippocampal mossy fiber sprouting and cognitive deficits following neonatal seizures, which might be a potential target of KD for the treatment of neonatal seizure-induced brain damage. Copyright © 2015 Elsevier B.V. All rights reserved.
Alexander V Lebedev
Full Text Available Cognitive impairment is a common non-motor feature of Parkinson’s disease (PD. The current study aimed to investigate resting state fMRI correlates of cognitive impairment in PD from a large-scale network perspective, and to assess the impact of dopamine deficiency on these networks. Thirty PD patients with resting state fMRI were included from the Parkinson’s Progression Marker Initiative (PPMI database. Eighteen patients from this sample were also scanned with 123I-FP-CIT SPECT. A standardized neuropsychological battery was administered, evaluating verbal memory, visuospatial, and executive cognitive domains. Image preprocessing was performed using an SPM8-based workflow, obtaining time-series from 90 regions-of-interest (ROIs defined from the AAL brain atlas. The Brain Connectivity Toolbox was used to extract nodal strength from all ROIs and modularity of the cognitive circuitry determined using the meta-analytical software Neurosynth. Brain-behavior covariance patterns between cognitive functions and nodal strength were estimated using Partial Least Squares. Extracted latent variable scores were correlated with performances in the three cognitive domains and striatal dopamine transporter binding ratios (SBR using linear modeling. Finally, influence of nigrostriatal dopaminergic deficiency on modularity of the cognitive network was analyzed. Less severe executive impairment was associated with increased dorsal fronto-parietal cortical processing and inhibited subcortical and primary sensory involvement. This pattern was positively influenced by the relative preservation of nigrostriatal dopaminergic function. The pattern associated with better memory performance favored prefronto-limbic processing, and did not reveal associations with presynaptic striatal dopamine uptake. SBR ratios were negatively associated with modularity of the cognitive network, suggesting integrative effects of the preserved nigrostriatal dopamine system on this
Li, Zheng-Qian; Rong, Xiao-Ying; Liu, Ya-Jie; Ni, Cheng; Tian, Xiao-Sheng; Mo, Na; Chui, De-Hua; Guo, Xiang-Yang
Highlights: •Isoflurane induces hippocampal IL-1β elevation and cognitive deficits in aged rats. •Isoflurane transiently activates the canonical NF-κB pathway in aged rat hippocampus. •NF-κB inhibitor mitigates isoflurane-induced IL-1β elevation and cognitive deficits. •We report a linkage between NF-κB signaling, IL-1β expression, and cognitive changes. -- Abstract: Although much recent evidence has demonstrated that neuroinflammation contributes to volatile anesthetic-induced cognitive deficits, there are few existing mechanistic explanations for this inflammatory process. This study was conducted to investigate the effects of the volatile anesthetic isoflurane on canonical nuclear factor (NF)-κB signaling, and to explore its association with hippocampal interleukin (IL)-1β levels and anesthetic-related cognitive changes in aged rats. After a 4-h exposure to 1.5% isoflurane in 20-month-old rats, increases in IκB kinase and IκB phosphorylation, as well as a reduction in the NF-κB inhibitory protein (IκBα), were observed in the hippocampi of isoflurane-exposed rats compared with control rats. These events were accompanied by an increase in NF-κB p65 nuclear translocation at 6 h after isoflurane exposure and hippocampal IL-1β elevation from 1 to 6 h after isoflurane exposure. Nevertheless, no significant neuroglia activation was observed. Pharmacological inhibition of NF-κB activation by pyrrolidine dithiocarbamate markedly suppressed the IL-1β increase and NF-κB signaling, and also mitigated the severity of cognitive deficits in the Morris water maze task. Overall, our results demonstrate that isoflurane-induced cognitive deficits may stem from upregulation of hippocampal IL-1β, partially via activation of the canonical NF-κB pathway, in aged rats
Yu, Mei; Zhang, Yuan; Chen, Xiaoyu; Zhang, Tao
The aim of this study was to examine whether amantadine (AMA), as a low-affinity noncompetitive N-methyl-d-aspartate (NMDA) receptor antagonist, is able to improve cognitive deficits caused by chronic stress in rats. Male Wistar rats were divided into four groups: control, control + AMA, stress and stress + AMA groups. The chronic stress model combined chronic unpredictable stress (CUS) with isolated feeding. Animals were exposed to CUS continued for 21 days. AMA (25 mg/kg) was administrated p.o. for 20 days from the 4th day of CUS to the 23rd. Weight and sucrose consumption were measured during model establishing period. Spatial memory was evaluated using the Morris water maze (MWM) test. Following MWM testing, both long-term potentiation (LTP) and depotentiation were recorded in the hippocampal CA1 region. NR2B and postsynaptic density protein 95 (PSD-95) proteins were measured by Western-blot analysis. AMA increased weight and sucrose consumption of stressed rats. Spatial memory and reversal learning in stressed rats were impaired relative to controls, whereas AMA significantly attenuated cognitive impairment. AMA also mitigated the chronic stress-induced impairment of hippocampal synaptic plasticity, in which both the LTP and depotentiation were significantly inhibited in stressed rats. Moreover, AMA enhanced the expression of hippocampal NR2B and PSD-95 in stressed rats. The data suggest that AMA may be an effective therapeutic agent for depression-like symptoms and associated cognitive disturbances.
Bikic, Aida; Christensen, Torben Østergaard; Leckman, James F; Bilenberg, Niels; Dalsgaard, Søren
The purpose of this trial was to examine the feasibility and efficacy of computerized cognitive exercises from Scientific Brain Training (SBT), compared to the computer game Tetris as an active placebo, in a pilot study of adolescents with attention-deficit/hyperactivity disorder (ADHD). Eighteen adolescents with ADHD were randomized to treatment or control intervention for 7 weeks. Outcome measures were cognitive test, symptom, and motivation questionnaires. SBT and Tetris were feasible as home-based interventions, and participants' compliance was high, but participants perceived both interventions as not very interesting or helpful. There were no significant group differences on cognitive and ADHD-symptom measures after intervention. Pre-post intra-group measurement showed that the SBT had a significant beneficial effect on sustained attention, while the active placebo had significant beneficial effects on working memory, both with large effect sizes. Although no significant differences were found between groups on any measure, there were significant intra-group changes for each group.
Diaz-Orueta, U; Fernandez-Fernandez, M A; Morillo-Rojas, M D; Climent, G
Lisdexanfetamine (LDX) is the drug for attention deficit hyperactivity disorder (ADHD) undergoing the largest research volume in the latest years. However, no studies certify its usefulness for the improvement of cognitive functioning in ADHD. To evaluate the efficacy of LDX in the behavioral and cognitive improvement of a group of patients with ADHD. Such efficacy was measured by means of the administration of AULA Nesplora virtual reality test before the prescription of pharmacological treatment and right after the treatment with LDX. The sample comprised 85 patients between 6 and 16 years, with clinical diagnosis of ADHD, who attended treatment in a neuropediatrics consultation. All patients started pharmacological treatment with the proper dose of LDX after the clinical interview and the first administration of AULA test. After an average treatment of 7.5 months, AULA was administered again and the treatment progress based on cognitive and motor symptomatology was assessed. Results showed highly significant improvements in selective and sustained attention, quality of attention focus and hyperactivity; moderate improvements in impulsivity; and an incidence close to zero in processing speed. LDX constitutes an adequate treatment for the substantial improvement of attention and hyperactivity; such improvement can be monitored accurately by means of AULA virtual reality test.
Schulz, Kurt P; Li, Xiaobo; Clerkin, Suzanne M; Fan, Jin; Berwid, Olga G; Newcorn, Jeffrey H; Halperin, Jeffrey M
The protracted and highly variable development of prefrontal cortex regions that support cognitive control has been purported to shape the adult outcome of attention-deficit/hyperactivity disorder (ADHD). This neurodevelopmental model was tested in a prospectively followed sample of 27 adult probands who were diagnosed with ADHD in childhood and 28 carefully matched comparison subjects aged 21-28 years. Probands were classified with persistent ADHD or remitted ADHD. Behavioral and neural responses to the Stimulus and Response Conflict Task (SRCT) performed during functional magnetic resonance imaging (fMRI) were compared in probands and comparison subjects and in probands with persistent and remitted ADHD. Response speed and accuracy for stimulus, response, and combined conflicts did not differ across groups. Orbitofrontal, inferior frontal and parietal activation was lower in probands than comparison subjects, but only for combined conflicts, when demand for cognitive control was highest. Reduced activation for combined conflicts in probands was almost wholly attributable to the persistence of ADHD; orbitofrontal, inferior frontal, anterior cingulate and parietal activation was lower in probands with persistent ADHD than both probands with remitted ADHD and comparison subjects, but did not differ between probands with remitted ADHD and comparison subjects. These data provide the first evidence that prefrontal and parietal activation during cognitive control parallels the adult outcome of ADHD diagnosed in childhood, with persistence of symptoms linked to reduced activation and symptom recovery associated with activation indistinguishable from adults with no history of ADHD. Copyright © 2017 Elsevier Ltd. All rights reserved.
Full Text Available Fragile X-associated tremor/ataxia syndrome (FXTAS is a late-onset neurodegenerative disorder that primarily affects males who are carriers of a premutation of a CGG expansion in the FMR1 gene. In Asian populations, FXTAS has rarely been reported. Here, we report the case of a Japanese FXTAS patient who showed predominant executive cognitive deficits as the main feature of his disease. In contrast, the patient exhibited only very mild symptoms of intention tremor and ataxia, which did not interfere with daily activities. A gene analysis revealed that the patient carried a premutation of a CGG expansion (111 CGG repeats in the FMR1 gene. The mRNA expression level of FMR1 in the patient was 1.5-fold higher than in controls. On brain MRI scans, fluid-attenuated inversion recovery images showed high-intensity lesions in the middle cerebellar peduncles and the cerebral white matter, with a frontal predominance. The present case extends previous notions regarding the cognitive impairment in FXTAS patients. Recognizing FXTAS patients with predominant cognitive impairment from various ethnic backgrounds would contribute to our understanding of the phenotypic variation of this disease.
705. Maren S. Pavlovian fear conditioning as a behavioral assay for hippocampus and amygdala function: cautions and caveats. Eur J Neurosci 2008;28... conditioning . Hear Res 2011;274:61–74. Weissman BA, Raveh L. Therapy against organophosphate poisoning: the importance of anticholinergic drugs with...whichmay lead to neuropathological damage and behavioral deficits. Caramiphen edisylate is an anticholinergic drug with antiglutamatergic properties
Luciana de Carvalho Monteiro
relationship to functional outcome and the effect of antipsychotics on cognition. METHOD: Research on databases such as Medline/PubMed and Lilacs using the terms schizophrenia, cognition, neuropsychology, outcome, functioning, treatment. RESULTS: Even though a great number of studies report cognitive impairments in schizophrenia, there is no agreement in relation to the pattern of these deficits. Nevertheless, cognitive impairments have a significant correlation with functional handicaps. Second generation antipsychotics seem to have a positive impact in cognition, although the meaning of this improvement on social and functional performance of the patients is not clear. Neuropsychological rehabilitation shows discrete, though promising, results. CONCLUSION: The ability of second generation antipsychotics to improve specific domains of cognition vary as does the pattern of deficits of the patients. Thus, strategies to improve cognition in schizophrenia include the use of second generation antipsychotics associated with neuropsychological rehabilitation.
Saddoris, Michael P; Carelli, Regina M
Cocaine use is often associated with diminished cognitive function, persisting even after abstinence from the drug. Likely targets for these changes are the core and shell of the nucleus accumbens (NAc), which are critical for mediating the rewarding aspects of drugs of abuse as well as supporting associative learning. To understand this deficit, we recorded neural activity in the NAc of rats with a history of cocaine self-administration or control subjects while they learned Pavlovian first- and second-order associations. Rats were trained for 2 weeks to self-administer intravenous cocaine or water. Later, rats learned a first-order Pavlovian discrimination where a conditioned stimulus (CS)+ predicted food, and a control (CS-) did not. Rats then learned a second-order association where, absent any food reinforcement, a novel cued (SOC+) predicted the CS+ and another (SOC-) predicted the CS-. Electrophysiological recordings were taken during performance of these tasks in the NAc core and shell. Both control subjects and cocaine-experienced rats learned the first-order association, but only control subjects learned the second-order association. Neural recordings indicated that core and shell neurons encoded task-relevant information that correlated with behavioral performance, whereas this type of encoding was abolished in cocaine-experienced rats. The NAc core and shell perform complementary roles in supporting normal associative learning, functions that are impaired after cocaine experience. This impoverished encoding of motivational behavior, even after abstinence from the drug, might provide a key mechanism to understand why addiction remains a chronically relapsing disorder despite repeated attempts at sobriety. Copyright © 2014 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
Pardini, Matteo; Serrati, Carlo; Guida, Silvia; Mattei, Chiara; Abate, Lucia; Massucco, Davide; Sassos, Davide; Amore, Mario; Krueger, Frank; Cocito, Leonardo; Emberti Gialloreti, Leonardo
Souvenaid™ is a nutraceutical compound thought to positively enhance synaptic function. In line with this mechanism of action, Souvenaid™ has been shown to improve cognitive function in subjects with mild Alzheimer's disease in randomized clinical trials. To date, however, the potential of Souvenaid™ to improve cognitive functioning in subjects with other neurodegenerative conditions also characterized by synaptic loss has not been explored. To evaluate the impact of Souvenaid™ on executive functions, social cognition and behavioral disturbances in subjects with the behavioral variant of frontotemporal dementia (bv-FTD). Twenty-six subjects with bv-FTD were enrolled in the study and randomized to Souvenaid™ (125 ml/day) or placebo groups. After 12 weeks, subjects were switched between the two groups. All subjects, blinded to treatment, underwent clinical and cognitive evaluations at enrollment, after 12 weeks and after 24 weeks. Treatment with Souvenaid™ was associated with a significant reduction of behavioral symptoms and an increase in Theory of Mind skills compared to placebo, which both returned to baseline when Souvenaid™ was discontinued. Souvenaid™ did not have an effect on executive functions. Our results provide evidence of the potential of Souvenaid™ therapy for the treatment of behavioral disturbances and social cognition skills in FTD. © 2015 S. Karger AG, Basel.
Rasmussen, Rune Skovgaard; Overgaard, K; Hildebrandt-Eriksen, E S
regarding gross motor performance. CONCLUSIONS: After embolization, physical therapy improved fine motor performance and D-amph accelerated rehabilitation of cognitive performance as observed in the rats of the THERAPY and D-AMPH groups. As a result of the administration of a high dose of D-amph, the rats......BACKGROUND AND PURPOSE: The purpose of this study was to examine the effects of D-amphetamine (D-amph) and physical therapy separately or combined on fine motor performance, gross motor performance and cognition after middle cerebral artery thromboembolization in rats. METHODS: Seventy-four rats...... on days 21-28 after surgery, rats of the SHAM and THERAPY groups had better fine motor performance than those of the CONTROL (P cognitive performance than CONTROL rats (P
Hahn-Markowitz, Jeri; Berger, Itai; Manor, Iris; Maeir, Adina
We examined the effect of the Cognitive-Functional (Cog-Fun) occupational therapy intervention on executive functions and participation among children with attention deficit hyperactivity disorder (ADHD). We used a randomized, controlled study with a crossover design. One hundred and seven children age 7-10 yr diagnosed with ADHD were allocated to treatment or wait-list control group. The control group received treatment after a 3-mo wait. Outcome measures included the Behavior Rating Inventory of Executive Function (BRIEF) and the Canadian Occupational Performance Measure (COPM). Significant improvements were found on both the BRIEF and COPM after intervention with large treatment effects. Before crossover, significant Time × Group interactions were found on the BRIEF. This study supports the effectiveness of the Cog-Fun intervention in improving executive functions and participation among children with ADHD. Copyright © 2017 by the American Occupational Therapy Association, Inc.
Full Text Available Background: Cognitive functions progressively deteriorate during aging and neurodegenerative diseases. The present study aims at investigating differences in working memory performance as well as functional brain changes during the earliest stages of cognitive decline in health elderly individuals. Methods: 62 elderly individuals (41 females, including 41 controls (35 females and 21 middle cognitive impairment subjects (6 females, underwent neuropsychological assessment at baseline and an fMRI examination in a N-back paradigm contrasting 2-back vs. 0-back condition. Upon a 18 months follow-up, we identified stable controls (sCON with preserved cognition and deteriorating controls (dCON with -1SD decrease of performances in at least two neuropsychological tests. Data analyses included accuracy and reaction time (RT for the 2-back condition and general linear model (GLM for the fMRI sequence. Results: At the behavioral level, sCON and dCON performed better than MCI in terms of accuracy and reaction time. At the brain level, functional differences in regions of the fronto-parietal network (FPN and of the Default Mode Network (DFM were observed. Significantly lower neural activations in the bilateral inferior and middle frontal gyri were found in MCI versus both dCON / sCON and for dCON versus sCON. Significantly increased activations in the anterior cingulate cortex and posterior cingulate cortex and bilateral insula were found in MCI versus both dCON / sCON and in dCON versus sCON. Conclusion: The present study suggests that brain functional changes in FPN and DMN anticipate differences in cognitive performance in healthy elderly individuals with subsequent subtle cognitive decline.
Bumoko G Makila-Mabe
Full Text Available We sought to determine whether motor and cognitive deficits associated with cassava (food cyanogenic poisoning were associated with high concentrations of F2-isoprostanes, well-established indicators of oxidative damage. Concentrations of serum F2-isoprostanes were quantified by LC-MS/MS and anchored to measures of motor proficiency and cognitive performance, which were respectively assessed through BOT-2 (Bruininks/Oseretsky Test, 2nd Edition and KABC-II (Kaufman Assessment Battery for Children, 2nd edition testing of 40 Congolese children (21 with konzo and 19 presumably healthy controls, overall mean age (SD: 9.3 (3.2 years. Exposure to cyanide was ascertained by concentrations of its main metabolite thiocyanate (SCN in plasma and urine. Overall, SCN concentrations ranged from 91 to 325 and 172 to 1032 µmol/l in plasma and urine, respectively. Serum isoprostanes ranged from 0.1 to 0.8 (Isoprostane-III, 0.8 to 8.3 (total Isoprostane-III, 0.1 to 1.5 (Isoprostane-VI, 2.0 to 9.0 (total Isoprostane-VI, or 0.2 to 1.3 ng/ml (8,12-iso-iPF2α-VI isoprostane. Children with konzo poorly performed at the BOT-2 and KABC-II testing relative to presumably healthy children (p<0.01. Within regression models adjusting for age, gender, motor proficiency, and other biochemical variables, 8,12-iso-iPF2α-VI isoprostane was significantly associated with the overall cognitive performance (β = -32.36 (95% CI: -51.59 to -13.03; P<0.001. This model explained over 85% of variation of the KABC-II score in children with konzo, but was not significant in explaining the motor proficiency impairment. These findings suggest that cognitive deficits and, possibly, brain injury associated with cassava poisoning is mediated in part by oxidative damage in children with konzo. 8,12-iso-iPF2α-VI isoprostane appears to be a good marker of the neuropathogenic mechanisms of konzo and may be used to monitor the impact of interventional trials to prevent the neurotoxic effects of
Rapanelli, Maximiliano; Frick, Luciana Romina; Bernardez-Vidal, Micaela; Zanutto, Bonifacio Silvano
Blockade of N-methyl-d-aspartate receptor (NMDA) by the noncompetitive NMDA receptor (NMDAR) antagonist MK-801 produces behavioral abnormalities and alterations in prefrontal cortex (PFC) functioning. Due to the critical role of the PFC in operant conditioning task learning, we evaluated the effects of acute, repeated postnatal injections of MK-801 (0.1mg/kg) on learning performance. We injected Long-Evans rats i.p. with MK-801 (0.1mg/kg) using three different administration schedules: injection 40 min before beginning the task (during) (n=12); injection twice daily for six consecutive days prior to beginning the experimental procedures (prior) (n=12); or twice daily subcutaneous injections from postnatal day 7 to 11 (postnatal) (n=12). Next, we orally administered risperidone (serotonin receptor 2A and dopamine receptor 2 antagonist, 1mg/kg) or buspirone (serotonin receptor 1A partial agonist, 10mg/kg) to animals treated with the MK-801 schedule described above. The postnatal and prior administration schedules produced severe learning deficits, whereas injection of MK-801 just before training sessions had only mild effects on acquisition of an operant conditioning. Risperidone was able to reverse the detrimental effect of MK-801 in the animals that were treated with MK-801 during and prior training sessions. In contrast, buspirone was only effective at mitigating the cognitive deficits induced by MK-801 when administered during the training procedures. The data demonstrates that NMDA antagonism disrupts basic mechanisms of learning in a simple PFC-mediated operant conditioning task, and that buspirone and risperidone failed to attenuate the learning deficits when NMDA neurotransmission was blocked in the early stages of the postnatal period. Copyright © 2013 Elsevier B.V. All rights reserved.
von Rhein, Daniel; Mennes, Maarten; van Ewijk, Hanneke; Groenman, Annabeth P; Zwiers, Marcel P; Oosterlaan, Jaap; Heslenfeld, Dirk; Franke, Barbara; Hoekstra, Pieter J; Faraone, Stephen V; Hartman, Catharina; Buitelaar, Jan
Attention-deficit/hyperactivity disorder (ADHD) is a persistent neuropsychiatric disorder which is associated with impairments on a variety of cognitive measures and abnormalities in structural and functional brain measures. Genetic factors are thought to play an important role in the etiology of ADHD. The NeuroIMAGE study is a follow-up of the Dutch part of the International Multicenter ADHD Genetics (IMAGE) project. It is a multi-site prospective cohort study designed to investigate the course of ADHD, its genetic and environmental determinants, its cognitive and neurobiological underpinnings, and its consequences in adolescence and adulthood. From the original 365 ADHD families and 148 control (CON) IMAGE families, consisting of 506 participants with an ADHD diagnosis, 350 unaffected siblings, and 283 healthy controls, 79 % participated in the NeuroIMAGE follow-up study. Combined with newly recruited participants the NeuroIMAGE study comprehends an assessment of 1,069 children (751 from ADHD families; 318 from CON families) and 848 parents (582 from ADHD families; 266 from CON families). For most families, data for more than one child (82 %) and both parents (82 %) were available. Collected data include a diagnostic interview, behavioural questionnaires, cognitive measures, structural and functional neuroimaging, and genome-wide genetic information. The NeuroIMAGE dataset allows examining the course of ADHD over adolescence into young adulthood, identifying phenotypic, cognitive, and neural mechanisms associated with the persistence versus remission of ADHD, and studying their genetic and environmental underpinnings. The inclusion of siblings of ADHD probands and controls allows modelling of shared familial influences on the ADHD phenotype.
Lu, Jun; Wu, Dong-Mei; Zheng, Yuan-Lin; Hu, Bin; Cheng, Wei; Zhang, Zi-Feng
Recent findings suggest that endoplasmic reticulum stress may be involved in the pathogenesis of domoic acid-induced neurodegeneration. Purple sweet potato color, a class of naturally occurring anthocyanins, has beneficial health and biological effects. Recent studies have also shown that anthocyanins have estrogenic activity and can enhance estrogen receptor-α expression. In this study, we evaluated the effect of purple sweet potato color on cognitive deficits induced by hippocampal mitochondrial dysfunction in domoic acid-treated mice and explored the potential mechanisms underlying this effect. Our results showed that the oral administration of purple sweet potato color to domoic acid-treated mice significantly improved their behavioral performance in a step-through passive avoidance task and a Morris water maze task. These improvements were mediated, at least in part, by a stimulation of estrogen receptor-α-mediated mitochondrial biogenesis signaling and by decreases in the expression of p47phox and gp91phox. Decreases in reactive oxygen species and protein carbonylation were also observed, along with a blockade of the endoplasmic reticulum stress pathway. Furthermore, purple sweet potato color significantly suppressed endoplasmic reticulum stress-induced apoptosis, which prevented neuron loss and restored the expression of memory-related proteins. However, knockdown of estrogen receptor-α using short hairpin RNA only partially blocked the neuroprotective effects of purple sweet potato color in the hippocampus of mice cotreated with purple sweet potato color and domoic acid, indicating that purple sweet potato color acts through multiple pathways. These results suggest that purple sweet potato color could be a possible candidate for the prevention and treatment of cognitive deficits in excitotoxic and other brain disorders. Crown Copyright © 2011. Published by Elsevier Inc. All rights reserved.
Famitafreshi, Hamidreza; Karimian, Morteza; Fatima, Sulail
Addiction to drugs of abuse is a devastating condition which results in deterioration of brain function. On the other hand, social isolation also produces cognitive deficits such as learning and memory impairment. This study was designed to evaluate the potential negative synergistic effects of social isolation and morphine addiction on brain functions. One hundred and two Sprague-Dawley rats were randomly divided into four groups for assessing neurogenesis and behaviour: group-housed, isolated, morphine-treated group-housed and morphine-treated isolated groups. Morphine- treated animals received BrdU (50 mg/kg; i.p.) and Morphine (0.75 mg/rat; i.p.) for 14 consecutive days, whereas, control rats received BrdU (50 mg/kg; i.p.) only. At the end of the study, Morris water maze and elevated plus maze tasks were performed to assess spatial working memory and anxiety levels, respectively. Furthermore, neurogenesis and BDNF levels were studied. Reference and working memory was markedly impaired in isolated and morphine-treated isolated rats as compared to group-housed rats and morphine-treated group-housed rats, respectively. Neurogenesis and BDNF levels were reduced in isolated and morphine-treated isolated rats as compared to group-housed rats and morphine-treated group-housed rats, respectively. Furthermore, rats in both isolated groups demonstrated low anxiety levels when compared to group housed groups. Isolation during addiction imparts devastating effects on brain. Thus, socialization of addicts can minimize addiction - induce cognitive deficits and improve neurogenesis.
Conclusions: Children and adolescents with ADHD and learning difficulties have more severe cognitive impairment than pure ADHD patients even after controlling for the effect of ADHD symptoms. However, the differences in impairment in inhibition and shift function are no longer significant when these individuals were 12–14 years old.
Bluschke, A; Roessner, V; Beste, C
Attention-deficit/hyperactivity disorder (ADHD) is one of the most prevalent neuropsychiatric disorders in childhood. Besides inattention and hyperactivity, impulsivity is the third core symptom leading to diverse and serious problems. However, the neuronal mechanisms underlying impulsivity in ADHD are still not fully understood. This is all the more the case when patients with the ADHD combined subtype (ADHD-C) are considered who are characterized by both symptoms of inattention and hyperactivity/impulsivity. Combining high-density electroencephalography (EEG) recordings with source localization analyses, we examined what information processing stages are dysfunctional in ADHD-C (n = 20) compared with controls (n = 18). Patients with ADHD-C made more impulsive errors in a Go/No-go task than healthy controls. Neurophysiologically, different subprocesses from perceptual gating to attentional selection, resource allocation and response selection processes are altered in this patient group. Perceptual gating, stimulus-driven attention selection and resource allocation processes were more pronounced in ADHD-C, are related to activation differences in parieto-occipital networks and suggest attentional filtering deficits. However, only response selection processes, associated with medial prefrontal networks, predicted impulsive errors in ADHD-C. Although the clinical picture of ADHD-C is complex and a multitude of processing steps are altered, only a subset of processes seems to directly modulate impulsive behaviour. The present findings improve the understanding of mechanisms underlying impulsivity in patients with ADHD-C and might help to refine treatment algorithms focusing on impulsivity.
Biscaro, Barbara; Lindvall, Olle; Tesco, Giuseppina; Ekdahl, Christine T; Nitsch, Roger M
Activated microglia with macrophage-like functions invade and surround β-amyloid (Aβ) plaques in Alzheimer's disease (AD), possibly contributing to the turnover of Aβ, but they can also secrete proinflammatory factors that may be involved in the pathogenesis of AD. Microglia are known to modulate adult hippocampal neurogenesis. To determine the role of microglia on neurogenesis in brains with Aβ pathology, we inhibited microglial activation with the tetracycline derivative minocycline in doubly transgenic mice expressing mutant human amyloid precursor protein (APP) and mutant human presenilin-1 (PS1). Minocycline increased the survival of new dentate granule cells in APP/PS1 mice indicated by more BrdU+/NeuN+ cells as compared to vehicle-treated transgenic littermates, accompanied by improved behavioral performance in a hippocampus-dependent learning task. Both brain levels of Aβ and Aβ-related morphological deficits in the new neurons labeled with GFP-expressing retrovirus were unaffected in minocycline-treated mice. These results suggest a role for microglia in Aβ-related functional deficits and in suppressing the survival of new neurons, and show that modulation of microglial function with minocycline can protect hippocampal neurogenesis in the presence of Aβ pathology. Copyright © 2012 S. Karger AG, Basel.
Warfarin administered to tumor-bearing mice reduces the number of spontaneous lung metastases. Both macrophage inhibitors silica and carrageenan abolish the warfarin-induced decrease in tumour metastasis, which strongly supports the concept that the antitumour effect of coumarin derivatives is
Humby, Trevor; Fisher, Amelia; Allen, Christopher; Reynolds, Meghann; Hartman, Annette; Giegling, Ina; Rujescu, Dan; Davies, William
The enzyme steroid sulfatase (STS) converts sulfated steroids to their non-sulfated forms. Deficiency for this enzyme is associated with inattention but preserved response control. The polymorphism rs17268988 within the X-linked STS gene is associated with inattentive, but not other, symptoms in boys with attention deficit hyperactivity disorder (ADHD). We initially tested whether rs17268988 genotype was associated with attention, response control, and underlying aspects of cognition, using questionnaires and neuropsychological tasks, in two independent cohorts of healthy adult males. In an additional analysis based upon existing data, the performance of mice with genetic or pharmacological manipulations of the STS axis under attentionally demanding conditions was investigated. G-allele carriers at rs17268988 exhibited reduced reaction time, enhanced attention, and reduced reaction time variability relative to C-allele carriers. Mice with genetic or pharmacological manipulations of the STS axis were shown to have perturbed reaction time variability. Our findings provide additional support for an association between rs17268988 genotype and attention, which may be partially mediated by reaction time variability; they also indicate that, in contrast to the situation in boys with ADHD, in healthy men, the G-allele at rs17268988 is associated with enhanced cognition. As reaction time variability is a predictor of well-being, rs17268988 genotype may represent a biomarker for long-term health.
Decreases of the sex steroids, testosterone and estrogen, are associated with increased risk of Alzheimer’s disease. Testosterone and estrogen supplementation improves cognitive deficits in animal models of Alzheimer’s disease. Sex hormones play a role in the regulation of amyloid-β via induction of the amyloid-β degrading enzymes neprilysin and insulin-degrading enzyme. To mimic the effect of dihydrotestosterone (DHT), we administered a selective androgen receptor agonist, ACP-105, alone and in combination with the selective estrogen receptor β (ERβ) agonist AC-186 to male gonadectomized triple transgenic mice. We assessed long-term spatial memory in the Morris water maze, spontaneous locomotion, and anxiety-like behavior in the open field and in the elevated plus maze. We found that ACP-105 given alone decreases anxiety-like behavior. Furthermore, when ACP-105 is administered in combination with AC-186, they increase the amyloid-β degrading enzymes neprilysin and insulin-degrading enzyme and decrease amyloid-β levels in the brain as well as improve cognition. Interestingly, the androgen receptor level in the brain was increased by chronic treatment with the same combination treatment, ACP-105 and AC-186, not seen with DHT or ACP-105 alone. Based on these results, the beneficial effect of the selective ERβ agonist as a potential therapeutic for Alzheimer’s disease warrants further investigation. PMID:24020966
Rana M. Zeina; Laila AL-Ayadhi; Shahid Bashir
The association between sensory problems and cognitive abilities has been studied in individuals with Autism Spectrum Disorders (ASDs). In this study, we used a Neuropsychological Test to evaluate memory and attention in ASDs children with sensory problems compared to the ASDs children without sensory problems. Four visual memory tests of Cambridge Neuropsychological Test Automated Battery (CANTAB) including Big/little circle (BLC), Simple Reaction Time (SRT) Intra /Extra dimensional set shif...
Zhou, Shanshan; Yu, Guichun; Chi, Lijun; Zhu, Jiwei; Zhang, Wei; Zhang, Yan; Zhang, Liming
Oxidative stress is implicated as an important factor in the development of Alzheimer's disease (AD). In the present study, we have investigated the effects of edaravone (9mg/kg, 3-methyl-1-phenyl-2-pyrazolin-5-one), a free radical scavenger, in a streptozotocin (STZ-3mg/kg) induced rat model of sporadic AD (sAD). Treatment with edaravone significantly improved STZ-induced cognitive damage as evaluated in Morris water maze and step-down tests and markedly restored changes in malondialdehyde (MDA), 4-hydroxy-2-nonenal (4-HNE) adducts, hydroxyl radical (OH), hydrogen peroxide (H2O2), total superoxide dismutase (T-SOD), reduced glutathione (GSH), glutathione peroxidase (GPx) and protein carbonyl (PC) levels. In addition, histomorphological observations confirmed the protective effect of edaravone on neuronal degeneration. Moreover, hyperphosphorylation of tau resulting from intracerebroventricular streptozotocin (ICV-STZ) injection was decreased by the administration of edaravone. These results provide experimental evidence demonstrating preventive effects of edaravone on cognitive dysfunction, oxidative stress and hyperphosphorylation of tau in ICV-STZ rats. Since edaravone has been used for treatment of patients with stroke, it represents a safe and established therapeutic intervention that has the potential for a novel application in the treatment of age-related neurodegenerative disorders associated with cognitive decline, such as AD. Copyright © 2013 The Authors. Published by Elsevier B.V. All rights reserved.
Full Text Available Background/Aims: TREM2 plays a crucial role in modulating microglial function through interaction with DAP12, the adapter for TREM2. Emerging evidence has demonstrated that TREM2 could suppress neuroinflammatory responses by repression of microglia-mediated cytokine production. This study investigated the potential role of TREM2 in surgery-induced cognitive deficits and neuroinflammatory responses in wild-type (WT and APPswe/PS1dE9 mice. Methods: Adult APPswe/PS1dE9 transgenic male mice (a classic transgenic model of Alzheimer’s disease, 3 months old and their age-matched WT mice received intracerebral lentiviral particles encoding the mouse TREM2 gene and then were subjected to partial hepatectomy at 1 month after the lentiviral particle injection. The behavioral changes were evaluated with an open-field test and Morris water maze test on postoperative days 3, 7, and 14. Hippocampal TREM2, DAP12, and interleukin (IL-1β were measured at each time point. Ionized calcium-binding adapter molecule 1 (Iba-1, microglial M2 phenotype marker Arg1, synaptophysin, tau hyperphosphorylation (T396, and glycogen synthase kinase-3β (GSK-3β were also examined in the hippocampus. Results: Surgical trauma induced an exacerbated cognitive impairment and enhanced hippocampal IL-1β expression in the transgenic mice on postoperative days 3 and 7. A corresponding decline in the levels of TREM2 was also found on postoperative days 3, 7, and 14. Overexpression of TREM2 downregulated the levels of IL-1β, ameliorated T396 expression, inhibited the activity of GSK-3β, and improved sickness behavior. Increased Arg1 expression and a high level of synaptophysin were also observed in the transgenic mice following TREM2 overexpression. Conclusion: The downregulation of TREM2 exacerbated surgery-induced cognitive deficits and exaggerated neuroinflammatory responses in this rodent model. Overexpression of TREM2 potentially attenuated these effects by decreasing the
Baroni, Argelinda; Castellanos, F Xavier
The ongoing release of the Human Connectome Project (HCP) data is a watershed event in clinical neuroscience. By attaining a quantum leap in spatial and temporal resolution within the framework of a twin/sibling design, this open science resource provides the basis for delineating brain-behavior relationships across the neuropsychiatric landscape. Here we focus on attention-deficit/hyperactivity disorder (ADHD), which is at least partly continuous across the population, highlighting constructs that have been proposed for ADHD and which are included in the HCP phenotypic battery. We review constructs implicated in ADHD (reward-related processing, inhibition, vigilant attention, reaction time variability, timing and emotional lability) which can be examined in the HCP data and in future 'high definition' clinical datasets. Copyright © 2014 Elsevier Ltd. All rights reserved.
Pan, Chien-Yu; Chu, Chia-Hua; Tsai, Chia-Liang; Lo, Shen-Yu; Cheng, Yun-Wen; Liu, Yu-Jen
The present study assessed the effects of a 12-week table tennis exercise on motor skills, social behaviors, and executive functions in children with attention deficit hyperactivity disorder (ADHD). In the first 12-week phase, 16 children (group I) received the intervention, whereas 16 children (group II) did not. A second 12-week phase immediately followed with the treatments reversed. Improvements were observed in executive functions in both groups after the intervention. After the first 12-week phase, some motor and behavioral functions improved in group I. After the second 12-week phase, similar improvements were noted for group II, and the intervention effects achieved in the first phase were persisted in group I. The racket-sport intervention is valuable in promoting motor skills, social behaviors, and executive functions and should be included within the standard-of-care treatment for children with ADHD. Copyright © 2016 Elsevier Ltd. All rights reserved.
莫胜男; 王波; 何珍; 孙昭; 邵珊珊; 宋然然
Objective To explore early cognitive deficits and clarify the main cognitive effects among children with dyslexia.Methods A cluster random sampling method was used to select 58 children from Grade 3-6 in a primary school in Wuhan.Among them there were 29 dyslexic children and 29 children without dyslexia.Each of them received six kinds of cognitive tests respectively.Analysis of covariance and discriminant analysis were used for data analysis.Results The scores of cognitive tests in the dyslexia group were lower in morphological awareness (15.76 ± 2.47),naming speed (2.48±0.56),working memory (6.08 ± 3.36),phonological short-term memory (6.03 ± 1.21) and phonological awareness (19.24 ± 6.14) than that in control group,and the differences were significantly (P ＜ 0.01).Three cognitive effects were selected into the discriminant equation,and the standardized discriminant function was Y =0.595 × speech short-term memory + 0.582 × working memory + 0.520 × phonological awareness.Conclusion There were five cognitive deficits existing in dyslexia children including morphological awareness,naming speeding,working memory,speech short-term memory and phonological awareness.The phonological awareness was the most important.The phonological awareness,speech short-term memory and working memory could be used as the early identification effects of dyslexia.%目的 了解阅读障碍儿童的早期认知缺陷,以及鉴别阅读障碍儿童的主要认知因素.方法 采用整群随机抽样方法,抽取武汉市某小学3～6年级58名小学生为研究对象,其中汉语阅读障碍和正常儿童各29名,对其分别进行6项认知能力测试.采用协方差分析和判别分析比较2组在6项认知能力之间的差异.结果 障碍组儿童在认知能力中语素意识(15.76 ±2.47)分、快速命名(2.48±0.56)分、工作记忆(6.08 ±3.36)分、语音短时记忆(6.03±1.21)分、语音意识(19.24±6.14)分均低于对照组,差异有统计学意义(P＜0
Schipper, Pieter; Henckens, Marloes J A G; Lopresto, Dora; Kozicz, Tamas; Homberg, Judith R
Life stress increases risk for developing post-traumatic stress disorder (PTSD), and more prominently so in short-allele carriers of the serotonin transporter linked polymorphic region (5-HTTLPR). Serotonin transporter knockout (5-HTT -/- ) rats show compromised extinction (recall) of conditioned fear, which might mediate the increased risk for PTSD and reduce the therapeutic efficacy of exposure therapy. Here, we assessed whether acute inescapable stress (IS) differentially affects fear extinction and extinction recall in 5-HTT -/- rats and wildtype controls. Surprisingly, IS experience improved fear extinction recall in 5-HTT -/- rats to the level of wildtype animals, while wildtypes were unaffected by this IS. Thus, whereas 5-HTT -/- rats evidently were more responsive to the stressor, the behavioral consequences presented themselves as adaptive. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.
Liu, Yang; Yan, Jiawei; Sun, Cao; Li, Guo; Li, Sirui; Zhang, Luwei; Di, Cuixia; Gan, Lu; Wang, Yupei; Zhou, Rong; Si, Jing; Zhang, Hong
Carbon ion therapy is a promising modality in radiotherapy to treat tumors, however, a potential risk of induction of late normal tissue damage should still be investigated and protected. The aim of the present study was to explore the long-term cognitive deficits provoked by a high-linear energy transfer (high-LET) carbon ions in mice by targeting to hippocampus which plays a crucial role in memory and learning. Our data showed that, one month after 4 Gy carbon ion exposure, carbon ion irradiation conspicuously resulted in the impaired cognitive performance, neurodegeneration and neuronal cell death, as well as the reduced mitochondrial integrity, the disrupted activities of tricarboxylic acid cycle flux and electron transport chain, and the depressed antioxidant defense system, consequently leading to a decline of ATP production and persistent oxidative damage in the hippocampus region. Mechanistically, we demonstrated the disruptions of mitochondrial homeostasis and redox balance typically characterized by the disordered mitochondrial dynamics, mitophagy and glutathione redox couple, which is closely associated with the inhibitions of PINK1 and NRF2 signaling pathway as the key regulators of molecular responses in the context of neurotoxicity and neurodegenerative disorders. Most importantly, we found that administration with melatonin as a mitochondria-targeted antioxidant promoted the PINK1 accumulation on the mitochondrial membrane, and augmented the NRF2 accumulation and translocation. Moreover, melatonin pronouncedly enhanced the molecular interplay between NRF2 and PINK1. Furthermore, in the mouse hippocampal neuronal cells, overexpression of NRF2/PINK1 strikingly protected the hippocampal neurons from carbon ion-elicited toxic insults. Thus, these data suggest that alleviation of the sustained mitochondrial dysfunction and oxidative stress through co-modulation of NRF2 and PINK1 may be in charge of restoration of the cognitive impairments in a mouse
DiGirolamo, Gregory J; Smelson, David; Guevremont, Nathan
Cue-induced craving is a clinically important aspect of cocaine addiction influencing ongoing use and sobriety. However, little is known about the relationship between cue-induced craving and cognitive control toward cocaine cues. While studies suggest that cocaine users have an attentional bias toward cocaine cues, the present study extends this research by testing if cocaine use disorder patients (CDPs) can control their eye movements toward cocaine cues and whether their response varied by cue-induced craving intensity. Thirty CDPs underwent a cue exposure procedure to dichotomize them into high and low craving groups followed by a modified antisaccade task in which subjects were asked to control their eye movements toward either a cocaine or neutral drug cue by looking away from the suddenly presented cue. The relationship between breakdowns in cognitive control (as measured by eye errors) and cue-induced craving (changes in self-reported craving following cocaine cue exposure) was investigated. CDPs overall made significantly more errors toward cocaine cues compared to neutral cues, with higher cravers making significantly more errors than lower cravers even though they did not differ significantly in addiction severity, impulsivity, anxiety, or depression levels. Cue-induced craving was the only specific and significant predictor of subsequent errors toward cocaine cues. Cue-induced craving directly and specifically relates to breakdowns of cognitive control toward cocaine cues in CDPs, with higher cravers being more susceptible. Hence, it may be useful identifying high cravers and target treatment toward curbing craving to decrease the likelihood of a subsequent breakdown in control. Copyright © 2015 Elsevier Ltd. All rights reserved.
Vidal, Blanca; Vázquez-Roque, Rubén A; Gnecco, Dino; Enríquez, Raúl G; Floran, Benjamin; Díaz, Alfonso; Flores, Gonzalo
Curcuma is a natural compound that has shown neuroprotective properties, and has been reported to prevent aging and improve memory. While the mechanism(s) underlying these effects are unclear, they may be related to increases in neural plasticity. Morphological changes have been reported in neuronal dendrites in the limbic system in animals and elderly humans with cognitive impairment. In this regard, there is a need to use alternative therapies that delay the onset of morphologies and behavioral characteristics of aging. Therefore, the objective of this study was to evaluate the effect of curcuma on cognitive processes and dendritic morphology of neurons in the prefrontal cortex (PFC), the CA1 and CA3 regions of the dorsal hippocampus, the dentate gyrus, and the basolateral amygdala (BLA) of aged rats. 18-month-old rats were administered curcuma (100 mg/kg) daily for 60 days. After treatment, recognition memory was assessed using the novel object recognition test. Curcuma-treated rats showed a significant increase in the exploration quotient. Dendritic morphology was assessed by Golgi-Cox staining and followed by Sholl analysis. Curcuma-treated rats showed a significant increase in dendritic spine density and dendritic length in pyramidal neurons of the PFC, the CA1 and CA3, and the BLA. The preservation of dendritic morphology was positively correlated with cognitive improvements. Our results suggest that curcuma induces modification of dendritic morphology in the aforementioned regions. These changes may explain how curcuma slows the aging process that has already begun in these animals, preventing deterioration in neuronal morphology of the limbic system and recognition memory. © 2016 Wiley Periodicals, Inc.
Full Text Available Exercise has been proposed for the treatment of traumatic brain injury (TBI. However, the proper intensity of exercise in the early phase following a severe TBI is largely unknown. To compare two different treadmill exercise intensities on the cognitive function following a severe TBI in its early phase, rats experienced a controlled cortical impact (CCI and were forced to treadmill exercise for 14 days. The results revealed that the rats in the low intensity exercise group had a shorter latency to locate a platform and a significantly better improvement in spatial memory in the Morris water maze (MWM compared to the control group (p 0.05. The brain-derived neurotrophic factor (BDNF and p-CREB protein levels in the contralateral hippocampus were increased significantly in the low intensity exercise group. Our results suggest that 2 weeks of low intensity of treadmill exercise is beneficial for improving cognitive function and increasing hippocampal BDNF expression after a severe TBI in its early phase.
Full Text Available Icariin (ICA, a prenylated flavanol glycoside present in abundant quantities in Epimedium sagittatum, has shown promise in the treatment and prevention of Alzheimer’s disease. Damage to synaptic plasticity induced by amyloid-beta-mediated neurotoxicity is considered a main pathological mechanism driving the learning and memory deficits present in patients with Alzheimer’s disease. This study investigated the neuroprotective effects of icariin in an Aβ1–42-induced rat model of Alzheimer’s disease. Our results showed that Aβ1–42 injection induced loss of learning and memory behaviour in the Morris water maze, which could be reversed with intragastric administration of ICA. Furthermore, ICA reversed decreases in PSD-95, BDNF, pTrkB, pAkt, and pCREB expressions and prevented deterioration of synaptic interface structure. These findings indicate that ICA may improve synaptic plasticity through the BDNF/TrkB/Akt pathway and provide further evidence for its clinical application to improve learning and memory in patients with Alzheimer’s disease.