In this study, we tested the hypothesis that action planning is impaired in children with neurofibromatosis type 1 (NF1). Thirty-six children with NF1 were pair-matched to 36 healthy controls (HC) on age (range, 7-12 years), sex, and parental education level, and both groups were administered three action-planning tasks. To examine the relation of task performance to attention deficit hyperactivity disorder (ADHD), the NF1 group was divided into subsets of children who met or did not meet criteria for ADHD. Children with NF1 performed less well than HC on all planning tasks, and differences remained when controlling for IQ or a measure of visuospatial skill. Both the NF1 with ADHD subset and NF1 without ADHD subset performed more poorly than HC on two of the tasks, whereas only the NF1 with ADHD subset performed worse than HC on the third planning task. The results underscore the importance of evaluating executive function in children with NF1 and suggest that deficits in this domain may be only partially related to ADHD. Planning deficits in children with NF1 may be part of their cognitive phenotype. Identifying these deficits is relevant in determining factors contributing to learning problems and in developing appropriate interventions.
"visuospatial functions, motor coordination, planning, organizational skills and reading/vocabulary) (Hofman et al., 1994; Hyman et al., 2005; Payne et al., 2011). This suggests a deficit in executive functions, which is consistent with more recent studies where a deficit in inhibitory control, working memory and cognitive flexibility as well as a global deficit in attention and executive functions were reported (Payne et al., 2011; Rowbotham et al., 2009; Roy et al., 2010). "
[Show abstract][Hide abstract] ABSTRACT: Intellectual disability, commonly known as mental retardation in the International Classification of Disease from World Health Organization, is the term that describes an intellectual and adaptive cognitive disability that begins in early life during the developmental period. Currently the term intellectual disability is the preferred one. Although our understanding of the physiological basis of learning and learning disability is poor, a general idea is that such condition is quite permanent. However, investigations in animal models suggest that learning disability can be functional in nature and as such reversible through pharmacology or appropriate learning paradigms. A fraction of the cases of intellectual disability is caused by point mutations or deletions in genes that encode for proteins of the RAS/MAP kinase signaling pathway known as RASopathies. Here we examined the current understanding of the molecular mechanisms involved in this group of genetic disorders focusing in studies which provide evidence that intellectual disability is potentially treatable and curable. The evidence presented supports the idea that with the appropriate understanding of the molecular mechanisms involved, intellectual disability could be treated pharmacologically and perhaps through specific mechanistic-based teaching strategies.
Journal of Physiology-Paris 05/2014; DOI:10.1016/j.jphysparis.2014.05.003. · 1.90 Impact Factor
"Our study cohort consisted of 30 patients with NF1 recruited from the Neurofibromatosis Clinic at the University Hospital in Nantes, France. Participants were drawn from a sample of children enrolled in a larger study on NF1 and EF (Roy et al., 2010). To be included, they had to fulfill the clinical criteria for the diagnosis of NF1 as specified by the National Institutes of Health Consensus Development Conference Statement (1988). "
[Show abstract][Hide abstract] ABSTRACT: Our study investigated spontaneous versus reactive cognitive flexibility in children with neurofibromatosis type 1 (NF1) and their comorbidity with attention-deficit hyperactivity disorder (ADHD). Thirty children with NF1 aged 7 to 12 years old were compared to 60 healthy controls matched by age, gender, and parental education. On the basis of Eslinger and Grattan's definition (199311.
Eslinger , P. J. , &
Grattan , L. M. ( 1993 ). Frontal lobe and frontal-striatal substrates for different forms of human cognitive flexibility , Neuropsychologia , 31 , 17 – 28 . [CrossRef], [PubMed], [Web of Science ®]View all references), spontaneous shifting was assessed using fluency tests, whereas reactive flexibility was measured by a child adaptation of the Modified Card-Sorting Test and the Brixton Test. IQ and basic skills were taken into account as confounding variables that might influence executive measures. NF1 children performed below the level of healthy children on both reactive flexibility tasks, even when intelligence and basic skills were partialled out, but ADHD symptomatology was not found to adversely affect the performance of patients. Our findings support the hypothesis of a specific executive impairment in NF1, uncovering a dissociation between (impaired) reactive flexibility and (preserved) spontaneous shifting, with no impact of ADHD on executive performance.
"Concerning the cognitive phenotype related to cortical functions, executive functions have been reported to be impaired in children with NF1 [59,69], even when controlling for IQ . Here, we observed lower LGI in several frontal lobe regions that could underlie executive impairments, namely the superior frontal gyri , right frontal pole and orbitofrontal regions [72,73]. "
[Show abstract][Hide abstract] ABSTRACT: Background
Neurofibromatosis type 1 (NF1) is a monogenic disorder associated with cognitive impairments. In order to understand how mutations in the NF1 gene impact brain structure it is essential to characterize in detail the brain structural abnormalities in patients with NF1. Previous studies have reported contradictory findings and have focused only on volumetric measurements. Here, we investigated the volumes of subcortical structures and the composite dimensions of the cortex through analysis of cortical volume, cortical thickness, cortical surface area and gyrification.
We studied 14 children with NF1 and 14 typically developing children matched for age, gender, IQ and right/left-handedness. Regional subcortical volumes and cortical gyral measurements were obtained using the FreeSurfer software. Between-group differences were evaluated while controlling for the increase in total intracranial volume observed in NF1.
Subcortical analysis revealed disproportionately larger thalami, right caudate and middle corpus callosum in patients with NF1. Cortical analyses on volume, thickness and surface area were however not indicative of significant alterations in patients. Interestingly, patients with NF1 had significantly lower gyrification indices than typically developing children primarily in the frontal and temporal lobes, but also affecting the insula, cingulate cortex, parietal and occipital regions.
The neuroanatomic abnormalities observed were localized to specific brain regions, indicating that particular areas might constitute selective targets for NF1 gene mutations. Furthermore, the lower gyrification indices were accompanied by a disproportionate increase in brain size without the corresponding increase in folding in patients with NF1. Taken together these findings suggest that specific neurodevelopmental processes, such as gyrification, are more vulnerable to NF1 dysfunction than others. The identified changes in brain organization are consistent with the patterns of cognitive dysfunction in the NF1 phenotype.
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