Developmental dyscalculia is not associated with atypical brain activation: A univariate fMRI study of arithmetic, magnitude processing, and visuospatial working memory.

Functional neuroimaging serves as a tool to better understand the cerebral correlates of atypical behaviors, such as learning difficulties. While significant advances have been made in characterizing the neural correlates of reading difficulties (developmental dyslexia), comparatively little is known about the neurobiological correlates of mathematical learning difficulties, such as developmental dyscalculia (DD). Furthermore, the available neuroimaging studies of DD are characterized by small sample sizes and variable inclusion criteria, which make it problematic to compare across studies. In addition, studies to date have focused on identifying single deficits in neuronal processing among children with DD (e.g., mental arithmetic), rather than probing differences in brain function across different processing domains that are known to be affected in children with DD. Here, we seek to address the limitations of prior investigations. Specifically, we used functional magnetic resonance imaging (fMRI) to probe brain differences between children with and without persistent DD; 68 children (8-10 years old, 30 with DD) participated in an fMRI study designed to investigate group differences in the functional neuroanatomy associated with commonly reported behavioral deficits in children with DD: basic number processing, mental arithmetic and visuo-spatial working memory (VSWM). Behavioral data revealed that children with DD were less accurate than their typically achieving (TA) peers for the basic number processing and arithmetic tasks. No behavioral differences were found for the tasks measuring VSWM. A pre-registered, whole-brain, voxelwise univariate analysis of the fMRI data from the entire sample of children (DD and TA) revealed areas commonly associated with the three tasks (basic number processing, mental arithmetic, and VSWM). However, the examination of differences in brain activation between children with and without DD revealed no consistent group differences in brain activation. In view of these null results, we ran exploratory, Bayesian analyses on the data to quantify the amount of evidence for no group differences. This analysis provides supporting evidence for no group differences across all three tasks. We present the largest fMRI study comparing children with and without persistent DD to date. We found no group differences in brain activation using univariate, frequentist analyses. Moreover, Bayesian analyses revealed evidence for the null hypothesis of no group differences. These findings contradict previous literature and reveal the need to investigate the neural basis of DD using multivariate and network-based approaches to brain imaging.

Altered resting-state functional connectivity in the prefrontal cortex is related to the development of dyscalculia in patients with Turner syndrome.

AIM: Patients with Turner syndrome have a high rate of developmental dyscalculia, but the underlying neurocognitive mechanisms are not well-understood. Some studies have implicated visuospatial impairments in patients with Turner syndrome, but others have focused on poor procedural skills in patients with Turner syndrome. This study used brain imaging data to test these two alternative views. METHODS: This study recruited 44 girls with Turner syndrome (mean age, 12.91 years; SD, 2.02), with 13 (29.5%) of them meeting the criterion for developmental dyscalculia, and 14 normally developing girls (mean age, 14.26 years; SD, 2.18) as a comparison group. All participants were given basic mathematical ability tests and an intelligence test and were scanned using magnetic resonance imaging. We compared patients with Turner syndrome who had dyscalculia, patients with Turner syndrome who did not have dyscalculia, and the normal controls in terms of brain structures and resting-state functional activity. RESULTS: Compared with normal controls, both groups of patients with Turner syndrome (with or without dyscalculia) showed similarly altered functional connectivity in the occipitoparietal dorsal stream. Importantly, compared with patients with Turner syndrome without dyscalculia and normal controls, patients with Turner syndrome with dyscalculia showed decreased functional connectivity between the prefrontal and the lateral occipital cortex. CONCLUSION: We concluded that both groups of patients with Turner syndrome shared visual deficits, and patients with Turner syndrome with dyscalculia had a deficit in frontal cortex-based higher cognitive processing. It is not their visuospatial deficits but rather their deficits in higher cognitive processing that are responsible for the development of dyscalculia in patients with Turner syndrome.

Severe developmental topographical disorientation associated with ADHD and dyscalculia: A case report.

We report the clinical case of AB, a right-handed 19-year-old woman who presents severe developmental topographical disorientation, a relatively rare syndrome, leading to difficulties in navigating in familiar (and novel) environments. This symptomatology appears without acquired cerebral damage (MRI described as normal) nor more global cognitive disability (high degree of education achieved). An extensive assessment of spatial cognition with different aspects of underlying cognitive processes is first presented. Second, the patient's preserved cognitive abilities and her major difficulties in calculation, as well as her attention deficit, as seen in a detailed neuropsychological assessment, are reported. For the first time to our knowledge, we show that developmental topographical disorientation can be associated with other developmental cognitive disorders affecting number processing (dyscalculia) and attention (Attention Deficit-Hyperactivity Disorder (ADHD)). We discuss the links between these different cognitive processes in relation to visuo-spatial working memory and magnitude representation, which could represent common denominators for all these syndromes. This case report highlights the importance of thoroughly assessing potentially associated neurocognitive disorders in developmental topographical disorientation. In addition, it highlights the necessity to keep in mind the prevalence of spatial difficulties in the assessment of children and adolescents with other neurodevelopmental syndromes. Finally, this case study raises a new question about the nosology of developmental disorders affecting the visuo-spatial and spatial domains.

Dorsal visual stream activity during coherent motion processing is not related to math ability or dyscalculia.

Math disability (MD) or developmental dyscalculia is a highly prevalent learning disability involving deficits in computation and arithmetic fact retrieval and is associated with dysfunction of parietal and prefrontal cortices. It has been suggested that dyscalculia (and other learning disabilities and developmental disorders) can be viewed in terms of a broader 'dorsal stream vulnerability,' which could explain a range of dorsal visual stream function deficits, including poor coherent visual motion perception. Behavioral evidence from two studies in typical children has linked performance on visual motion perception to math ability, and a third behavioral study reported poorer visual motion perception in a small group of children with MD compared to controls. Visual motion perception relies on the magnocellular-dominated dorsal stream, particularly its constituent area V5/MT. Here we used functional MRI to measure brain activity in area V5/MT during coherent visual motion processing to test its relationship with math ability. While we found bilateral activation in V5/MT in 66 children/adolescents with varied math abilities, we found no relationships between V5/MT activity and standardized math measures. Next, we selected a group of children/adolescents with MD (n = 23) and compared them to typically developing controls (n = 18), but found no differences in activity in V5/MT or elsewhere in the brain. We followed these frequentist statistics with Bayesian analyses, which favored null models in both studies. We conclude that dorsal stream function subserving visual motion processing in area V5/MT is not related to math ability, nor is it altered in those with the math disability dyscalculia.

Reduced 2D form coherence and 3D structure from motion sensitivity in developmental dyscalculia.

Developmental dyscalculia (DD) is a specific learning disability affecting the development of numerical and arithmetical skills. The origin of DD is typically attributed to the suboptimal functioning of key regions within the dorsal visual stream (parietal cortex) which support numerical cognition. While DD individuals are often impaired in visual numerosity perception, the extent to which they also show a wider range of visual dysfunctions is poorly documented. In the current study we measured sensitivity to global motion (translational and flow), 2D static form (Glass patterns) and 3D structure from motion in adults with DD and control subjects. While sensitivity to global motion was comparable across groups, thresholds for static form and structure from motion were higher in the DD compared to the control group, irrespective of associated reading impairments. Glass pattern sensitivity predicted numerical abilities, and this relation could not be explained by recently reported differences in visual crowding. Since global form sensitivity has often been considered an index of ventral stream function, our findings could indicate a cortical dysfunction extending beyond the dorsal visual stream. Alternatively, they would fit with a role of parietal cortex in form perception under challenging conditions requiring multiple element integration.

Increased structural covariance in brain regions for number processing and memory in children with developmental dyscalculia.

Developmental dyscalculia (DD) is a developmental learning disability associated with deficits in processing numerical and mathematical information. Several studies demonstrated functional network alterations in DD. Yet, there are no studies, which examined the structural network integrity in DD. We compared whole-brain maps of volume based structural covariance between 19 (4 males) children with DD and 18 (4 males) typically developing children. We found elevated structural covariance in the DD group between the anterior intraparietal sulcus to the middle temporal and frontal gyrus (p < 0.05, corrected). A hippocampus subfield analysis showed higher structural covariance in the DD group for area CA3 to the parahippocampal and calcarine sulcus, angular gyrus and anterior part of the intraparietal sulcus as well as to the lingual gyrus. Lower structural covariance in this group was seen for the subiculum to orbitofrontal gyrus, anterior insula and middle frontal gyrus. In contrast, the primary motor cortex (control region) revealed no difference in structural covariance between groups. Our results extend functional magnetic resonance studies by revealing abnormal gray matter integrity in children with DD. These findings thus indicate that the pathophysiology of DD is mediated by both structural and functional abnormalities in a network involved in number processing and memory function.

Volumetric and surface characteristics of gray matter in adult dyslexia and dyscalculia.

Dyslexia, dyscalculia and their comorbid manifestation are prevalent disorders associated with well-documented behavioral manifestations. However, attempts to relate these manifestations to abnormalities in brain structure have yielded mixed results, with no clear consistency across a range of measures. In this study, we used a unique design including adults with dyslexia, dyscalculia, both disorders and controls, to explore differences in gray matter characteristics across groups. Specifically, we examined whether dyslexia, dyscalculia, or their comorbid manifestation could be related to volumetric and surface characteristics of gray matter, using voxel-based and surface-based morphometry. We demonstrate with Bayesian analyses that the present data favor the null model of no differences between groups across the brain, a result that is in line with recent findings in this field of research. Importantly, we provide detailed statistical maps to enable robust assessment of our findings, and to promote cumulative evaluation of the evidence. Together, these findings suggest that gray matter differences associated with dyslexia and dyscalculia might not be as reliable as suggested by previous literature, with important implications for our understanding of these disorders.

Brain SPECT scans in students with specific learning disability: Preliminary results.

Background and Objectives: Brain single-photon emission computed tomography (SPECT) assesses brain function through measurement of regional cerebral blood flow. This study was conducted to assess whether students with newly diagnosed specific learning disability (SpLD) show any abnormalities in cerebral cortex perfusion. Settings and Design: Cross-sectional single-arm pilot study in two tertiary care hospitals. Subjects and Methods: Nine students with SpLD were enrolled. Brain SPECT scan was done twice in each student. For the first or "baseline" scan, the student was first made to sit with eyes open in a quiet, dimly lit room for a period of 30-40 min and then injected intravenously with 20 mCi of 99mTc-ECD. An hour later, "baseline scan" was conducted. After a minimum gap of 4 days, a second or "test scan" was conducted, wherein the student performed an age-appropriate curriculum-based test for a period of 30-40 min to activate the areas in central nervous system related to learning before being injected with 20 mCi of 99mTc-ECD. Statistical Analysis Used: Cerebral cortex perfusion at rest and after activation in each student was compared qualitatively by visual analysis and quantitatively using NeuroGam™ software. Results: Visual analysis showed reduction in regional blood flow in temporoparietal areas in both "baseline" and "test" scans. However, when normalization was attempted and comparison done by Talairach analysis using NeuroGam software, no statistically significant change in regional perfusion in temporoparietal areas was appreciated. Conclusion: Brain SPECT scan may serve as a robust tool to identify changes in regional brain perfusion in students with SpLD.

Multi-method brain imaging reveals impaired representations of number as well as altered connectivity in adults with dyscalculia.

Two hypotheses have been proposed about the etiology of neurodevelopmental learning disorders, such as dyslexia and dyscalculia: representation impairments and disrupted access to representations. We implemented a multi-method brain imaging approach to directly investigate these representation and access hypotheses in dyscalculia, a highly prevalent but understudied neurodevelopmental disorder in learning to calculate. We combined several magnetic resonance imaging methods and analyses, including univariate and multivariate analyses, functional and structural connectivity. Our sample comprised 24 adults with dyscalculia and 24 carefully matched controls. Results showed a clear deficit in the non-symbolic magnitude representations in parietal, temporal and frontal regions, as well as hyper-connectivity in visual brain regions in adults with dyscalculia. Dyscalculia in adults was thereby related to both impaired number representations and altered connectivity in the brain. We conclude that dyscalculia is related to impaired number representations as well as altered access to these representations.

Tactile enumeration: A case study of acalculia.

Enumeration is one of the building blocks of arithmetic and fingers are used as a counting tool in early steps. Subitizing-fast and accurate enumeration of small quantities-has been vastly studied in the visual modality, but less in the tactile modality. We explored tactile enumeration using fingers, and gray matter (GM) changes using voxel-based morphometry (VBM), in acalculia. We examined JD, a 22-year-old female with acalculia following a stroke to the left inferior parietal cortex. JD and a neurologically healthy normal comparison (NC) group reported how many fingers were stimulated. JD was tested at several time points, including at acute and chronic phases. Using the sensory intact hand for tactile enumeration, JD showed deficit in the acute phase, compared to the NC group, and improvement in the chronic phase of (1) the RT slope of enumerating up to four stimuli, (2) enumerating neighboring fingers, and (3) arithmetic fluency performance. Moreover, VBM analysis showed a larger GM volume for JD relative to the NC group in the right middle occipital cortex, most profoundly in the chronic phase. JD's performance serves as a first glance of tactile enumeration in acalculia. Pattern-recognition-based results support the suggestion of subitizing being the enumeration process when using one hand. Moreover, the increase in GM in the occipital cortex lays the groundwork for studying the innate and primitive ability to perceive and evaluate sizes or amounts-"sense of magnitude"- as a multisensory magnitude area and as part of a recovery path for deficits in basic numerical abilities.

Dislexia y discalculia: una revisión sistemática actual desde la neurogenética / Dyslexia and Dyscalculia: a Current Systematic Revision from a Neurogenetics Perspective

Resumen Los Trastornos Específicos del Aprendizaje constituyen un grupo heterogéneo de alteraciones frecuentes que pueden generar problemas importantes no solo durante la etapa escolar, sino a lo largo de toda la vida. Las dificultades persistentes en lectura (dislexia) y en matemáticas (discalculia) son, por su relevancia y prevalencia, los dos Trastornos de Aprendizaje más importantes en la práctica educativa y clínica. El objetivo del estudio es realizar una síntesis de los descubrimientos científicos de los últimos diez años sobre las bases neuroanatómicas y genéticas de la dislexia y la discalculia. Se realizó un análisis exhaustivo bibliográfico desde 2006 hasta enero de 2017 en inglés y español centrados en neuroimagen y genética de dislexia y discalculia mediante las bases de datos Medline, PsyInfo, Scopus, Web of Science y Dialnet. Se incluyeron 38 artículos de los cuales se extrajeronn las aportaciones desde la neuroimagen y la genética tanto para la dislexia como de discalculia. Estos datos facilitaron herramientas para orientar al contexto psicológico y educativo, a su vez proporcionando respuestas definitivas.

Abstract The Specific Learning Disorders represent a heterogeneous group of common conditions that can generate important problems not only during schooling but also throughout life. The persistent difficulties in reading (dyslexia) and maths (dyscalculia) are, due to their significance and prevalence, the two most important learning disorders in both educational and clinical practice. The objective of this study is to make a synthesis of the scientific findings of the past ten years about neuroanatomical and genetic basis of dyslexia and dyscalculia. To this aim a comprehensive bibliographic analysis is conducted from 2006 until January, 2017 in English and Spanish from databases Medline, PsyInfo, Scopus, Web of Science y Dialnet. There were included 43 articles with contributions so much about dyslexia as dyscalculia from the neuroimagen and the genetics. This information will provide tools to guide psychological and educational environments and to provide definitive answers.

Acute stroke presenting with isolated acalculia.

Acalculia is defined as the inability to mentally manipulate numbers for simple calculations. It may occur in dementia, central nervous system (CNS) neoplasm, and stroke (Bermejo-Velasco and Castillo-Moreno, 2006). Lesions of the left parietal cortex are the principal cause. When acalculia occurs in stroke, it is generally associated with other deficits in speech, sensation, or motor function. We report the case of a 63-year-old male with a 1 day history of isolated acalculia that was found to have a left parietal lobe infarct with several smaller infarcts in the left occipital lobe. The diagnosis of stroke should be considered in all patients experiencing acute difficulty with mathematics, reading, or writing, even in the absence of other deficits.

Dyscalculia and dyslexia: Different behavioral, yet similar brain activity profiles during arithmetic.

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.

The Progressive Acalculia Presentation of Parietal Variant Alzheimer's Disease.

BACKGROUND: Many patients with early-onset Alzheimer's disease (EOAD; age of onset <65 years) have non-amnestic presentations involving language (logopenic primary progressive aphasia, lvPPA), visuospatial abilities (posterior cortical atrophy, PCA), and even asymmetric symptoms consistent with corticobasal syndrome (CBS). An inferior parietal lobule variant of EOAD commonly presents with progressive difficulty with calculations. METHODS: We reviewed 276 EOAD patients for presentations with predominant acalculia. These patients were diagnosed with clinically probable Alzheimer's disease (AD) verified by positron emission tomography (PET) or cerebrospinal fluid amyloid-ß or tau biomarkers. RESULTS: We identified 18 (9M/9F) (6.5%) EOAD patients with progressive acalculia that did not meet most criteria for lvPPA, visual PCA, or CBS. Their ages of onset and presentation were 56.6 (5.0) and 59.4 (6.5), respectively. Their acalculia was consistent with a primary acalculia ("anarithmetia") not explained by language or visuospatial impairments. Many also had anomia (14/18), ideomotor apraxia (13/18), and the complete Gerstmann's syndrome (7/18). Visual analysis of their diverse magnetic resonance imaging disclosed biparietal atrophy, disproportionately worse on the left. CONCLUSIONS: Primary acalculia may be the most common manifestation of an inferior parietal presentation of EOAD affecting the left intraparietal sulcus. This parietal variant also commonly involves progressive anomia, ideomotor apraxia, and other elements of Gerstmann's syndrome. The early recognition of patients with this variant, which is distinguishable from lvPPA, visual PCA, or CBS, would be facilitated by its recognition as a unique subtype of EOAD.

No evidence for systematic white matter correlates of dyslexia and dyscalculia.

Learning disabilities such as dyslexia, dyscalculia and their comorbid manifestation are prevalent, affecting as much as 15% of the population. Structural neuroimaging studies have indicated that these disorders can be related to differences in white matter integrity, although findings remain disparate. In this study, we used a unique design composed of individuals with dyslexia, dyscalculia, both disorders and controls, to systematically explore differences in fractional anisotropy across groups using diffusion tensor imaging. Specifically, we focused on the corona radiata and the arcuate fasciculus, two tracts associated with reading and mathematics in a number of previous studies. Using Bayesian hypothesis testing, we show that the present data favor the null model of no differences between groups for these particular tracts-a finding that seems to go against the current view but might be representative of the disparities within this field of research. Together, these findings suggest that structural differences associated with dyslexia and dyscalculia might not be as reliable as previously thought, with potential ramifications in terms of remediation.

Re-assessing acalculia: Distinguishing spatial and purely arithmetical deficits in right-hemisphere damaged patients.

Arithmetical deficits in right-hemisphere damaged patients have been traditionally considered secondary to visuo-spatial impairments, although the exact relationship between the two deficits has rarely been assessed. The present study implemented a voxelwise lesion analysis among 30 right-hemisphere damaged patients and a controlled, matched-sample, cross-sectional analysis with 35 cognitively normal controls regressing three composite cognitive measures on standardized numerical measures. The results showed that patients and controls significantly differ in Number comprehension, Transcoding, and Written operations, particularly subtractions and multiplications. The percentage of patients performing below the cutoffs ranged between 27% and 47% across these tasks. Spatial errors were associated with extensive lesions in fronto-temporo-parietal regions -which frequently lead to neglect- whereas pure arithmetical errors appeared related to more confined lesions in the right angular gyrus and its proximity. Stepwise regression models consistently revealed that spatial errors were primarily predicted by composite measures of visuo-spatial attention/neglect and representational abilities. Conversely, specific errors of arithmetic nature linked to representational abilities only. Crucially, the proportion of arithmetical errors (ranging from 65% to 100% across tasks) was higher than that of spatial ones. These findings thus suggest that unilateral right hemisphere lesions can directly affect core numerical/arithmetical processes, and that right-hemisphere acalculia is not only ascribable to visuo-spatial deficits as traditionally thought.

Diagnosing developmental dyscalculia on the basis of reliable single case FMRI methods: promises and limitations.

FMRI-studies are mostly based on a group study approach, either analyzing one group or comparing multiple groups, or on approaches that correlate brain activation with clinically relevant criteria or behavioral measures. In this study we investigate the potential of fMRI-techniques focusing on individual differences in brain activation within a test-retest reliability context. We employ a single-case analysis approach, which contrasts dyscalculic children with a control group of typically developing children. In a second step, a support-vector machine analysis and cluster analysis techniques served to investigate similarities in multivariate brain activation patterns. Children were confronted with a non-symbolic number comparison and a non-symbolic exact calculation task during fMRI acquisition. Conventional second level group comparison analysis only showed small differences around the angular gyrus bilaterally and the left parieto-occipital sulcus. Analyses based on single-case statistical procedures revealed that developmental dyscalculia is characterized by individual differences predominantly in visual processing areas. Dyscalculic children seemed to compensate for relative under-activation in the primary visual cortex through an upregulation in higher visual areas. However, overlap in deviant activation was low for the dyscalculic children, indicating that developmental dyscalculia is a disorder characterized by heterogeneous brain activation differences. Using support vector machine analysis and cluster analysis, we tried to group dyscalculic and typically developing children according to brain activation. Fronto-parietal systems seem to qualify for a distinction between the two groups. However, this was only effective when reliable brain activations of both tasks were employed simultaneously. Results suggest that deficits in number representation in the visual-parietal cortex get compensated for through finger related aspects of number representation in fronto-parietal cortex. We conclude that dyscalculic children show large individual differences in brain activation patterns. Nonetheless, the majority of dyscalculic children can be differentiated from controls employing brain activation patterns when appropriate methods are used.