126,236 research outputs found
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Mechanism and treatment for learning and memory deficits in mouse models of Noonan syndrome.
In Noonan syndrome (NS) 30-50% of subjects show cognitive deficits of unknown etiology and with no known treatment. Here, we report that knock-in mice expressing either of two NS-associated mutations in Ptpn11, which encodes the nonreceptor protein tyrosine phosphatase Shp2, show hippocampal-dependent impairments in spatial learning and deficits in hippocampal long-term potentiation (LTP). In addition, viral overexpression of an NS-associated allele PTPN11(D61G) in adult mouse hippocampus results in increased baseline excitatory synaptic function and deficits in LTP and spatial learning, which can be reversed by a mitogen-activated protein kinase kinase (MEK) inhibitor. Furthermore, brief treatment with lovastatin reduces activation of the GTPase Ras-extracellular signal-related kinase (Erk) pathway in the brain and normalizes deficits in LTP and learning in adult Ptpn11(D61G/+) mice. Our results demonstrate that increased basal Erk activity and corresponding baseline increases in excitatory synaptic function are responsible for the LTP impairments and, consequently, the learning deficits in mouse models of NS. These data also suggest that lovastatin or MEK inhibitors may be useful for treating the cognitive deficits in NS
Exploring Essential Characteristics of Self-Determination for Diverse Students Using Data From NLTS2
This study explored the impact of race/ethnicity on three of the four essential characteristics of self-determination—autonomy, self-realization, and psychological empowerment—directly assessed in the National Longitudinal Transition Study-2. Specifically, the impact of race/ethnicity was examined with six disability groups established in previous research: high incidence disabilities (learning disabilities, emotional disturbances, speech language impairments, and other health impairments), sensory disabilities (visual and hearing impairments), cognitive disabilities (autism, multiple disabilities, and deaf-blindness); intellectual disability, traumatic brain injury, and orthopedic impairments. Measurement equivalence was established across groups, but significant differences in the latent means, variances, and covariances were found suggesting a complex pattern of differences based on race/ethnicity within disability groups. Implications for future research and practice are discussed
The effect of training intensity on implicit learning rates in schizophrenia
Cognitive impairments in learning and memory are core symptoms of schizophrenia, associated with reduced self-reported quality of life. The most effective treatment of cognitive impairments is drill and practice cognitive training. Still, to date no study has investigated the effect of varying the frequency of training on cognitive outcomes. Here we utilized a verbal memory based language learning task, tapping into implicit cognitive processes, to investigate the role of training intensity on learning rates in individuals with schizophrenia. Data from 47 participants across two studies was utilized, one with a daily training regimen over 5 days and the other with a more intensive schedule of 5 sessions delivered over 2 days. The primary outcome measure was the change in implicit learning performance across five sessions, quantified with the Matthews Correlation Coefficient (MCC). Participants in the daily training group showed improved performance compared to the intensive group only at session 4. This is the first study to show that implicit learning rates are influenced by training intensity, with daily sessions outperforming a more intensive regimen; a period of consolidation overnight may be necessary to optimize cognitive training for individuals with schizophrenia
Supporting children with genetic syndromes in the classroom: the example of 22q deletion syndrome
An increasing number of children are likely to have a known genetic cause for their special educational needs. One such genetic condition is 22q11.2 deletion syndrome (22qDS), a genetic syndrome associated with early speech and language difficulties, global and specific cognitive impairments, difficulties with attention and difficulties with social-emotional functioning. In this article the learning and behavioural strengths and needs of this genetic syndrome are described along with recommendations for classroom-based interventions. Suggested recommendations in the learning and emotional-behavioural domains for the syndrome draw on a number of approaches that have been found to be useful for children with a range of conditions including ADHD, ASD and dyscalculia. While teachers cannot be expected to know about all potential genetic causes for special educational needs, knowing that a genetic condition is likely to be associated with a pattern of relative cognitive and behavioural strengths and needs is important
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Developmental divergence: motor trajectories in children with fragile X syndrome with and without co-occurring autism.
BackgroundAutism spectrum disorder (ASD) is highly prevalent in fragile X syndrome (FXS), affecting 50-70% of males. Motor impairments are a shared feature across autism and FXS that may help to better characterize autism in FXS. As motor skills provide a critical foundation for various language, cognitive, and social outcomes, they may serve an important mechanistic role for autism in FXS. As such, this study aimed to identify differences in motor trajectories across direct assessment and parent-report measures of fine and gross motor development between FXS with and without autism, and typical development, while controlling for cognitive functioning.MethodsThis prospective longitudinal study included 42 children with FXS, 24 of whom also had ASD (FXS + ASD), as well as 40 typically developing children. The Mullen Scales of Early Learning provided a direct measure of fine and gross motor skills, and the Vineland Adaptive Behavior Scales provided a measure of parent-reported fine and gross motor skills. Random slopes and random intercepts multilevel models were tested to determine divergence in developmental motor trajectories between groups when controlling for cognitive level.ResultsModel results indicated the children with FXS + ASD diverged from TD children by 9-months on all measures of gross and fine motor skills, even when controlling for cognitive level. Results also indicated an early divergence in motor trajectories of fine and gross motor skills between the FXS + ASD and FXS groups when controlling for cognitive level. This divergence was statistically significant by 18 months, with the FXS + ASD showing decelerated growth in motor skills across direct observation and parent-report measures.ConclusionsThis study is the first to examine longitudinal trends in motor development in children with FXS with and without comorbid ASD using both direct assessment and parent-report measures of fine and gross motor. Furthermore, it is among the first to account for nonverbal cognitive delays, a step towards elucidating the isolated role of motor impairments in FXS with and without ASD. Findings underscore the role of motor impairments as a possible signal representing greater underlying genetic liability, or as a potential catalyst or consequence, of co-occurring autism in FXS
Touchscreen-based cognitive tasks reveal age-related impairment in a primate aging model, the grey mouse lemur (Microcebus murinus)
Mouse lemurs are suggested to represent promising novel non-human primate models for aging research. However, standardized and cross-taxa cognitive testing methods are still lacking. Touchscreen-based testing procedures have proven high stimulus control and reliability in humans and rodents. The aim of this study was to adapt these procedures to mouse lemurs, thereby exploring the effect of age. We measured appetitive learning and cognitive flexibility of two age groups by applying pairwise visual discrimination (PD) and reversal learning (PDR) tasks. On average, mouse lemurs needed 24 days of training before starting with the PD task. Individual performances in PD and PDR tasks correlate significantly, suggesting that individual learning performance is unrelated to the respective task. Compared to the young, aged mouse lemurs showed impairments in both PD and PDR tasks. They needed significantly more trials to reach the task criteria. A much higher inter-individual variation in old than in young adults was revealed. Furthermore, in the PDR task, we found a significantly higher perseverance in aged compared to young adults, indicating an age-related deficit in cognitive flexibility. This study presents the first touchscreen-based data on the cognitive skills and age-related dysfunction in mouse lemurs and provides a unique basis to study mechanisms of inter-individual variation. It furthermore opens exciting perspectives for comparative approaches in aging, personality, and evolutionary research
Neuropsychological Functioning of Homeless Men
Numerous biological and psychological factors associated with impaired neurological functioning have been identified as common among the homeless, but there has been relatively little systematic examination of the cognitive functioning of homeless people. This study explored the neuropsychological functioning of 90 homeless men. There was great variability in their test scores, but the presence of possible cognitive impairment was detected in 80% of the sample. Average general intellectual functioning and reading abilities were found to be relatively low, and the incidence of impairments in reading, new verbal learning, memory, and attention and concentration was high. These findings suggest that the homeless men in this study had considerable assessment and treatment needs that were not being met by most of the health and social services offered to them
Profiling executive dysfunction in adults with autism and comorbid learning disability
Executive dysfunction is thought to be primary to autism. We examined differences in executive function between 20 adults with autism and learning disability and 23 individuals with learning disabilities outside the autistic spectrum. All participants were matched for chronological age and full-scale IQ, and were given a battery of tasks assessing fluency, planning, set-shifting, inhibition and working memory. Analyses of the individual tasks revealed very few significant differences between the two groups. However, analyses of composite scores derived for each executive domain revealed that the group with autism showed impaired performance on the working memory and planning tests. Together, these two measures were sufficient to classify participants into their diagnostic groups significantly better than would be expected by chance (75% of the autism group; 65% of the control group). Executive impairments were neither universal nor exclusive to the autism group, and we suggest that an alternative cognitive theory may better explain the cognitive profile we found
Cognitive performance in multiple system atrophy
The cognitive performance of a group of patients with multiple system atrophy (MSA) of striato-nigral predominance was compared with that of age and IQ matched control subjects, using three tests sensitive to frontal lobe dysfunction and a battery sensitive to memory and learning deficits in Parkinson's disease and dementia of the Alzheimer type. The MSA group showed significant deficits in all three of the tests previously shown to be sensitive to frontal lobe dysfunction. Thus, a significant proportion of patients from the MSA group failed an attentional set-shifting test, specifically at the stage when an extra-dimensional shift was required. They were also impaired in a subject-ordered test of spatial working memory. The MSA group showed deficits mostly confined to measures of speed of thinking, rather than accuracy, on the Tower of London task. These deficits were seen in the absence of consistent impairments in language or visual perception. Moreover, the MSA group showed no significant deficits in tests of spatial and pattern recognition previously shown to be sensitive to patients early in the course of probable Alzheimer's disease and only a few patients exhibited impairment on the Warrington Recognition Memory Test. There were impairments on other tests of visual memory and learning relative to matched controls, but these could not easily be related to fundamental deficits of memory or learning. Thus, on a matching-to-sample task the patients were impaired at simultaneous but not delayed matching to sample, whereas difficulties in a pattern-location learning task were more evident at its initial, easier stages. The MSA group showed no consistent evidence of intellectual deterioration as assessed from their performance on subtests of the Wechsler Adult Intelligence Scale (WAIS) and the National Adult Reading Test (NART). Consideration of individual cases showed that there was some heterogeneity in the pattern of deficits in the MSA group, with one patient showing no impairment, even in the face of considerable physical disability. The results show a distinctive pattern of cognitive deficits, unlike those previously seen using the same tests in patients with Parkinson's and Alzheimer's diseases, and suggesting a prominent frontal-lobe-like component. The implications for concepts of 'subcortical' dementia and 'fronto-striatal' cognitive dysfunction are considered
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