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Frontiers in Neurology 2023Carriers of Fragile X premutation may have associated medical comorbidities, such as Fragile X-associated tremor and ataxia (FXTAS) and Fragile X-associated premature...
OBJECTIVE
Carriers of Fragile X premutation may have associated medical comorbidities, such as Fragile X-associated tremor and ataxia (FXTAS) and Fragile X-associated premature ovarian insufficiency (FXPOI). We examined the Fragile X premutation effect on cognition, and we assumed that there is a direct correlation between the continuous spectrum of specific learning and attention deficits to the number of CGG repeats on the gene.
METHODS
A total of 108 women were referred to our center due to a related Fragile X syndrome (FXS) patient, 79 women carried a premutation of 56-199 repeats, and 19 women carried a full mutation of more than 200 CGG repeats on gene. Genetic results of CGG repeats, demographic information, structured questionnaires for ADHD, learning disabilities of language and mathematics, and independence level were analyzed in women carrying the premutation and compared to the group carrying the full mutation. Women with FXS and FXTAS were excluded.
RESULTS
When analyzed as a continuum, there was a significant increase in the following complaints which were associated with a higher number of repeats: specific daily function skills such as driving a car, writing checks, disorientation in directions, and also specific learning difficulties such as spelling and math difficulties. Additionally, when tested as a categorical independent variable, we observe that women with the full mutation were more likely to have ADHD or other learning disability diagnoses in the past than during premutation (<200 CGG repetitions).
CONCLUSION
Specific learning and attention difficulties and resulting daily function difficulties correlate with an increased number of CGG repeats and are more likely to be associated as a common feature of premutation and full mutation in a female premutation carrier. Despite evidence of learning and attention difficulties, it is encouraging that most female carriers of the premutation and full mutation function well in most areas. Nevertheless, they face significant difficulties in specific areas of functioning such as driving, and confusion in times and schedules. Those daily function skills are mostly impacted by dyscalculia, right and left disorientation, and attention difficulties. This may aid to design specific interventions to address specific learning deficits in order to improve daily function skills and quality of life.
PubMed: 37200782
DOI: 10.3389/fneur.2023.1135630 -
Journal of Learning Disabilities 2013The primary goal of this review is to highlight current research and theories describing the neurobiological basis of math (MD), reading (RD), and comorbid math and... (Review)
Review
The primary goal of this review is to highlight current research and theories describing the neurobiological basis of math (MD), reading (RD), and comorbid math and reading disability (MD+RD). We first describe the unique brain and cognitive processes involved in acquisition of math and reading skills, emphasizing similarities and differences in each domain. Next we review functional imaging studies of MD and RD in children, integrating relevant theories from experimental psychology and cognitive neuroscience to characterize the functional neuroanatomy of cognitive dysfunction in MD and RD. We then review recent research on the anatomical correlates of MD and RD. Converging evidence from morphometry and tractography studies are presented to highlight distinct patterns of white matter pathways which are disrupted in MD and RD. Finally, we examine how the intersection of MD and RD provides a unique opportunity to clarify the unique and shared brain systems which adversely impact learning and skill acquisition in MD and RD, and point out important areas for future work on comorbid learning disabilities.
Topics: Brain; Comorbidity; Dyscalculia; Dyslexia; Humans
PubMed: 23572008
DOI: 10.1177/0022219413483174 -
Philosophical Transactions of the Royal... Feb 2017One specific cause of low numeracy is a deficit in a mechanism for representing and processing numerosities that humans inherited and which is putatively shared with... (Review)
Review
One specific cause of low numeracy is a deficit in a mechanism for representing and processing numerosities that humans inherited and which is putatively shared with many other species. This deficit is evident at each of the four levels of explanation in the 'causal modelling' framework of Morton and Frith (Morton and Frith 1995 In , vol. 1 (eds D Cichetti, D Cohen), pp. 357-390). Very low numeracy can occur in cognitively able individuals with normal access to good education: it is linked to an easily measured deficit in basic numerosity processing; it has a distinctive neural signature; and twin studies suggest specific heritability, though the relevant genes have not yet been identified. Unfortunately, educators and policymakers seem largely unaware of this cause, but appropriate interventions could alleviate the suffering and handicap of those with low numeracy, and would be a major benefit to society.This article is part of a discussion meeting issue 'The origins of numerical abilities'.
Topics: Comprehension; Education; Humans; Mathematical Concepts
PubMed: 29292351
DOI: 10.1098/rstb.2017.0118 -
Developmental Medicine and Child... Nov 2007There is a growing consensus that the neuropsychological underpinnings of developmental dyscalculia (DD) are a genetically determined disorder of 'number sense', a term... (Review)
Review
There is a growing consensus that the neuropsychological underpinnings of developmental dyscalculia (DD) are a genetically determined disorder of 'number sense', a term denoting the ability to represent and manipulate numerical magnitude nonverbally on an internal number line. However, this spatially-oriented number line develops during elementary school and requires additional cognitive components including working memory and number symbolization (language). Thus, there may be children with familial-genetic DD with deficits limited to number sense and others with DD and comorbidities such as language delay, dyslexia, or attention-deficit-hyperactivity disorder. This duality is supported by epidemiological data indicating that two-thirds of children with DD have comorbid conditions while one-third have pure DD. Clinically, they differ according to their profile of arithmetic difficulties. fMRI studies indicate that parietal areas (important for number functions), and frontal regions (dominant for executive working memory and attention functions), are under-activated in children with DD. A four-step developmental model that allows prediction of different pathways for DD is presented. The core-system representation of numerical magnitude (cardinality; step 1) provides the meaning of 'number', a precondition to acquiring linguistic (step 2), and Arabic (step 3) number symbols, while a growing working memory enables neuroplastic development of an expanding mental number line during school years (step 4). Therapeutic and educational interventions can be drawn from this model.
Topics: Brain; Child; Cognition Disorders; Developmental Disabilities; Humans; Mathematics; Severity of Illness Index
PubMed: 17979867
DOI: 10.1111/j.1469-8749.2007.00868.x -
NPJ Science of Learning Jul 2021The development of numerical and arithmetic abilities constitutes a crucial cornerstone in our modern and educated societies. Difficulties to acquire these central... (Review)
Review
The development of numerical and arithmetic abilities constitutes a crucial cornerstone in our modern and educated societies. Difficulties to acquire these central skills can lead to severe consequences for an individual's well-being and nation's economy. In the present review, we describe our current broad understanding of the functional and structural brain organization that supports the development of numbers and arithmetic. The existing evidence points towards a complex interaction among multiple domain-specific (e.g., representation of quantities and number symbols) and domain-general (e.g., working memory, visual-spatial abilities) cognitive processes, as well as a dynamic integration of several brain regions into functional networks that support these processes. These networks are mainly, but not exclusively, located in regions of the frontal and parietal cortex, and the functional and structural dynamics of these networks differ as a function of age and performance level. Distinctive brain activation patterns have also been shown for children with dyscalculia, a specific learning disability in the domain of mathematics. Although our knowledge about the developmental brain dynamics of number and arithmetic has greatly improved over the past years, many questions about the interaction and the causal involvement of the abovementioned functional brain networks remain. This review provides a broad and critical overview of the known developmental processes and what is yet to be discovered.
PubMed: 34301948
DOI: 10.1038/s41539-021-00099-3 -
NeuroImage. Clinical 2018Brain disorders are often investigated in isolation, but very different conclusions might be reached when studies directly contrast multiple disorders. Here, we...
Brain disorders are often investigated in isolation, but very different conclusions might be reached when studies directly contrast multiple disorders. Here, we illustrate this in the context of specific learning disorders, such as dyscalculia and dyslexia. While children with dyscalculia show deficits in arithmetic, children with dyslexia present with reading difficulties. Furthermore, the comorbidity between dyslexia and dyscalculia is surprisingly high. Different hypotheses have been proposed on the origin of these disorders (number processing deficits in dyscalculia, phonological deficits in dyslexia) but these have never been directly contrasted in one brain imaging study. Therefore, we compared the brain activity of children with dyslexia, children with dyscalculia, children with comorbid dyslexia/dyscalculia and healthy controls during arithmetic in a design that allowed us to disentangle various processes that might be associated with the specific or common neural origins of these learning disorders. Participants were 62 children aged 9 to 12, 39 of whom had been clinically diagnosed with a specific learning disorder (dyscalculia and/or dyslexia). All children underwent fMRI scanning while performing an arithmetic task in different formats (dot arrays, digits and number words). At the behavioral level, children with dyscalculia showed lower accuracy when subtracting dot arrays, and all children with learning disorders were slower in responding compared to typically developing children (especially in symbolic formats). However, at the neural level, analyses pointed towards substantial neural similarity between children with learning disorders: Control children demonstrated higher activation levels in frontal and parietal areas than the three groups of children with learning disorders, regardless of the disorder. A direct comparison between the groups of children with learning disorders revealed similar levels of neural activation throughout the brain across these groups. Multivariate subject generalization analyses were used to statistically test the degree of similarity, and confirmed that the neural activation patterns of children with dyslexia, dyscalculia and dyslexia/dyscalculia were highly similar in how they deviated from neural activation patterns in control children. Collectively, these results suggest that, despite differences at the behavioral level, the brain activity profiles of children with different learning disorders during arithmetic may be more similar than initially thought.
Topics: Brain; Child; Dyscalculia; Dyslexia; Female; Humans; Magnetic Resonance Imaging; Male; Mathematics; Problem Solving
PubMed: 29876258
DOI: 10.1016/j.nicl.2018.03.003 -
BMJ Neurology Open 2023IRF2BPL (interferon regulatory factor 2-binding protein-like) gene is an intronless gene present ubiquitously in the human body, including the brain. Pathogenic variants...
BACKGROUND
IRF2BPL (interferon regulatory factor 2-binding protein-like) gene is an intronless gene present ubiquitously in the human body, including the brain. Pathogenic variants lead to neurodegeneration and present with phenotypic features of a neurological disorder, including dyslexia, dyscalculia, epilepsy, dystonia, neurodevelopmental regression, loss of motor skills and cerebellar ataxia.
CASE
We present a case of a 9-year-old boy who was brought to the emergency department with generalised tonic-clonic seizures and mild hypotonia. A history included neurological regression. After insignificant lab and imaging results, the patient underwent genetic testing, revealing a novel pathogenic mutation in the IRF2BPL gene (heterozygous variant), which had never been reported in the literature before. An autosomal dominant loss of function mutation was demonstrated, denoting in DNA as NM_0 24 496 c.911 C>T, which results in premature protein termination (p.Glu494).
CONCLUSION
Our case highlights the importance of early recognition of the neurological symptoms associated with various IRF2BPL gene mutations so that a timely multidisciplinary management approach can be provided.
PubMed: 37649702
DOI: 10.1136/bmjno-2023-000459 -
Frontiers in Human Neuroscience 2021Dyscalculia is a learning disability affecting the acquisition of arithmetical skills in children with normal intelligence and age-appropriate education. Two hypotheses...
Dyscalculia is a learning disability affecting the acquisition of arithmetical skills in children with normal intelligence and age-appropriate education. Two hypotheses attempt to explain the main cause of dyscalculia. The first hypothesis suggests that a problem with the core mechanisms of perceiving (non-symbolic) quantities is the cause of dyscalculia (core deficit hypothesis), while the alternative hypothesis suggests that dyscalculics have problems only with the processing of numerical symbols (access deficit hypothesis). In the present study, the symbolic and non-symbolic numerosity processing of typically developing children and children with dyscalculia were examined with functional magnetic resonance imaging (fMRI). Control ( = 15, mean age: 11.26) and dyscalculia ( = 12, mean age: 11.25) groups were determined using a wide-scale screening process. Participants performed a quantity comparison paradigm in the fMRI with two number conditions (dot and symbol comparison) and two difficulty levels (0.5 and 0.7 ratio). The results showed that the bilateral intraparietal sulcus (IPS), left dorsolateral prefrontal cortex (DLPFC) and left fusiform gyrus (so-called "number form area") were activated for number perception as well as bilateral occipital and supplementary motor areas. The task difficulty engaged bilateral insular cortex, anterior cingulate cortex, IPS, and DLPFC activation. The dyscalculia group showed more activation in the left orbitofrontal cortex, left medial prefrontal cortex, and right anterior cingulate cortex than the control group. The dyscalculia group showed left hippocampus activation specifically for the symbolic condition. Increased left hippocampal and left-lateralized frontal network activation suggest increased executive and memory-based compensation mechanisms during symbolic processing for dyscalculics. Overall, our findings support the access deficit hypothesis as a neural basis for dyscalculia.
PubMed: 34354576
DOI: 10.3389/fnhum.2021.687476 -
Translational Psychiatry Apr 2017Several copy number variants have been associated with neuropsychiatric disorders and these variants have been shown to also influence cognitive abilities in carriers...
Several copy number variants have been associated with neuropsychiatric disorders and these variants have been shown to also influence cognitive abilities in carriers unaffected by psychiatric disorders. Previously, we associated the 15q11.2(BP1-BP2) deletion with specific learning disabilities and a larger corpus callosum. Here we investigate, in a much larger sample, the effect of the 15q11.2(BP1-BP2) deletion on cognitive, structural and functional correlates of dyslexia and dyscalculia. We report that the deletion confers greatest risk of the combined phenotype of dyslexia and dyscalculia. We also show that the deletion associates with a smaller left fusiform gyrus. Moreover, tailored functional magnetic resonance imaging experiments using phonological lexical decision and multiplication verification tasks demonstrate altered activation in the left fusiform and the left angular gyri in carriers. Thus, by using convergent evidence from neuropsychological testing, and structural and functional neuroimaging, we show that the 15q11.2(BP1-BP2) deletion affects cognitive, structural and functional correlates of both dyslexia and dyscalculia.
Topics: Adolescent; Adult; Aged; Chromosome Aberrations; Chromosome Deletion; Chromosomes, Human, Pair 15; Cognition; DNA Copy Number Variations; Developmental Disabilities; Dyscalculia; Dyslexia; Female; Functional Neuroimaging; Heterozygote; Humans; Iceland; Intellectual Disability; Magnetic Resonance Imaging; Male; Middle Aged; Neuropsychological Tests; Phenotype; Temporal Lobe; Young Adult
PubMed: 28440815
DOI: 10.1038/tp.2017.77 -
Frontiers in Psychology 2022Mathematics is a struggle for many. To make it more accessible, behavioral and educational scientists are redesigning how it is taught. To a similar end, a few rogue... (Review)
Review
Mathematics is a struggle for many. To make it more accessible, behavioral and educational scientists are redesigning how it is taught. To a similar end, a few rogue mathematicians and computer scientists are doing something more radical: they are redesigning mathematics itself, improving its ergonomic features. Charles Peirce, an important contributor to ordinary symbolic logic, also introduced a rigorous but non-symbolic, graphical alternative to it that is easier to picture. In the spirit of this , George Spencer-Brown founded . Performing iconic arithmetic, algebra, and even trigonometry, resembles doing calculations on an abacus, which is still popular in education today, has aided humanity for millennia, helps even when it is merely imagined, and ameliorates severe disability in basic computation. Interestingly, whereas some intellectually disabled individuals excel in very complex numerical tasks, others of normal intelligence fail even in very simple ones. A comparison of their wider psychological profiles suggests that iconic mathematics ought to suit the very people traditional mathematics leaves behind.
PubMed: 35769758
DOI: 10.3389/fpsyg.2022.890362