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.

[A case of suspected migraine with aura: transient cortical venous dilatation visualized by susceptibility-weighted imaging].

A 41-year-old man was admitted with proper name anomia and headache of sudden onset. He had a history of migraine without aura from the age of 35. Neurological examination on admission showed acalculia, proper name anomia, left-right disorientation and severe left-sided headache with nausea. Susceptibility-weighted MRI revealed dilatation of cortical veins of the left hemisphere. MR angiography and contrast CT revealed no cerebral arterial or venous occlusion. The patient's proper name anomia was improved at 5 hours from the onset and acalculia and left-right disorientation were improved at 17 hours from the onset. At 42 hours from the onset, he had recovered from his headache, and the dilatation of cortical veins of the left hemisphere had disappeared. Acalculia and left and right disorientation are rare presentations of migraine with aura. Susceptibility-weighted imaging may be a useful tool to distinguish migraine with aura from stroke and stroke mimics.

Dystypia Associated with Diaschisis of the Middle Frontal Gyri after Left Angular Infarction.

Dystypia without aphasia, agraphia, or apraxia is a rare symptom and has been suggested to result from a lesion in the left middle frontal cortex. We herein describe a man with dystypia with agraphia due to infarction of the left angular gyrus. His dystypia seemed to result from the convergence failure of the kana into the alphabetical spellings. During dystypia, hypoperfusion of the bilateral middle frontal cortices was discovered. However, after his symptoms improved, blood flow in the middle frontal cortices returned to normal. This case suggests that the middle frontal cortex is downstream of the angular gyrus in the dictating pathway and a lesion in the left middle frontal cortex could cause pure dystypia.

A Rare Clinical Antity; Pure Gerstmann Syndrome.

Gerstmann syndrome is defined as a tetrad including agraphia, acalculia, finger agnosia, and right-left disorientation. In the case studies presented in the literature, it has been reported that Gerstmann syndrome usually appears as an incomplete tetrad of symptoms or accompanied by cognitive deficits including aphasia, alexia, apraxia and some perceptual disorders. Here, we present of the patient with left angular and supramarginal gyrus infarction affecting the parietal lobe. In addition to the symptoms mentioned above, the patient had alexia and anomic aphasia as well. We discussed the clinic appearance and reviewed the current literature.

Understanding Comorbidity Between Specific Learning Disabilities.

Current definitions of specific learning disability (SLD) identify a heterogeneous population that includes individuals with weaknesses in reading, math, or writing, and these academic difficulties often co-occur in many of the same individuals. The Colorado Learning Disabilities Research Center (CLDRC) is an interdisciplinary, multisite research program that uses converging levels of analysis to understand the genetic and environmental etiology, neuropsychology, and developmental outcomes of SLDs in reading (RD), math (MD), and writing (WD), along with the comorbidity between these SLDs and other developmental disorders. The latest results from the CLDRC twin study suggest that shared genetic influences contribute to the significant covariance between all aspects of reading (word reading, reading fluency, and reading comprehension) and math (calculations, math fluency, and word problems), and distinct genetic or environmental influences also contribute to weaknesses in each specific academic domain. RD and MD are associated with a range of negative outcomes on both concurrent measures and measures of functional outcomes completed 5 years after the twins were first assessed. Over the next several years the CLDRC will continue to expand on this work by administering a comprehensive test battery that includes measures of all dimensions of academic achievement that are described in current definitions of SLD and incorporating these measures in new neuroimaging and molecular genetic studies.

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.

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.

Numerical magnitude processing impairments in genetic syndromes: a cross-syndrome comparison of Turner and 22q11.2 deletion syndromes.

Cross-syndrome comparisons offer an important window onto understanding heterogeneity in mathematical learning disabilities or dyscalculia. The present study therefore investigated symbolic numerical magnitude processing in two genetic syndromes that are both characterized by mathematical learning disabilities: Turner syndrome and 22q11.2 deletion syndrome (22q11DS). We further verified whether the phenotypic outcomes of these syndromes emerged from the same or different cognitive processes and therefore examined whether numerical impairments were related to working memory deficits, often observed in these syndromes. Participants were 24 girls with Turner syndrome, 25 children with 22q11DS and 48 well-matched typically developing control children. All children completed a symbolic numerical magnitude comparison task and four additional working memory tasks. Both groups of children with genetic syndromes showed similar impairments in symbolic numerical magnitude processing compared to typically developing controls. Importantly, in Turner syndrome, group differences in symbolic numerical magnitude processing disappeared when their difficulties in visual-spatial working memory were taken into account. In contrast, the difficulties in 22q11DS were not explained by poor visual-spatial working memory. These data suggest that different factors underlie the symbolic numerical magnitude processing impairments in both patient groups with mathematical learning disabilities and highlight the value of cross-syndrome comparisons for understanding different pathways to mathematical learning disabilities or dyscalculia.

[Differential diagnosis of primary and secondary mathematical learning disability ­ indications from the dyscalculia test Basis-Math 4­8]. / Differenzialdiagnose zwischen primärer Rechenstörung und sekundärer Rechenschwäche: Hinweise aus dem Basis-Math 4-8.

Studies in children with AD(H)D without mathematical learning disability (MLD) as well as studies on the effects of methylphenidate on arithmetic have shown that most deficits in mathematics and most error types commonly described as specific to developmental dyscalculia (e. g., finger-counting, fact-retrieval deficit, complex counting, difficulties with carry/borrow procedures, self-corrections) cannot be classified as such and should thus not be used for the differential diagnosis of primary dyscalculia and secondary MLD. This article proposes using the overall score in the dyscalculia test Basis-Math 4-8 (Moser Opitz et al., 2010) as well as implausible subtraction errors as a marker for dyscalculia and the number of self-corrections made during the test as a cognitive marker for attention deficits. Hierarchical cluster analyses were calculated in a sample of 51 clinically referred children with normal IQ and suspicion of MLD, using IQ, years of schooling, overall score of the Basis-Math 4­8 and number of self-corrections in this test as variables. The results revealed a subgroup with primary dyscalculia as well as three subgroups with secondary MLD (two with attention deficit hyperactivity disorder, one with depression and one small subgroup with high IQ). In conclusion, the Basis-Math 4­8 (Moser Opitz et al., 2010) can offer substantial information for the differential diagnosis of dyscalculia and secondary deficits in mathematics due to attention problems and enable optimization of treatment decisions for the different groups.

A meta-analysis of math performance in Turner syndrome.

AIM: Studies investigating the relationship between Turner syndrome and math learning disability have used a wide variation of tasks designed to test various aspects of mathematical competencies. Although these studies have revealed much about the math deficits common to Turner syndrome, their diversity makes comparisons between individual studies difficult. As a result, the consistency of outcomes among these diverse measures remains unknown. The overarching aim of this review is to provide a systematic meta-analysis of the differences in math and number performance between females with Turner syndrome and age-matched neurotypical peers. METHOD: We provide a meta-analysis of behavioral performance in Turner syndrome relative to age-matched neurotypical populations on assessments of math and number aptitude. In total, 112 comparisons collected across 17 studies were included. RESULTS: Although 54% of all statistical comparisons in our analyses failed to reject the null hypothesis, our results indicate that meaningful group differences exist on all comparisons except those that do not require explicit calculation. INTERPRETATION: Taken together, these results help elucidate our current understanding of math and number weaknesses in Turner syndrome, while highlighting specific topics that require further investigation.

Ecological Assessment Battery for Numbers (EABN) for brain-damaged patients: standardization and validity study.

OBJECTIVES: Number-processing may be altered following brain injury and might affect the everyday life of patients. We developed the first ecological tool to assess number-processing disorders in brain-injured patients, the Ecological Assessment Battery for Numbers (EABN; in French, the BENQ). The aim of the present study was to standardize and validate this new tool. MATERIAL AND METHODS: Standardization included 126 healthy controls equally distributed by age, sex and sociocultural level. First, 17 patients were evaluated by the EABN; then scores for a subgroup of 10 were compared with those from a French analytical calculation test, the Évaluation Clinique des Aptitudes Numériques (ECAN). The concordance between the EABN and the ECAN was analyzed to determine construct validity. Discrimination indexes were calculated to assess the sensitivity of the subtests. RESULTS: Standardization highlighted a major effect of sociocultural level. In total, 9 of 17 patients had a pathological EABN score, with difficulties in telling time, making appointments and reading numerical data. The results of both the EABN and ECAN tests were concordant (Kendall's w=0.97). Finally, the discriminatory power was good, particularly for going to the movies, cheque-writing and following a recipe: scores were>0.4. CONCLUSION: The EABN is a new tool to assess number-processing disorders in adults. This tool has been standardized and has good psychometric properties for patients with brain injury.

Biparietal variant of Alzheimer's disease: a rare presentation of a common disease.

Alzheimer's disease (AD) is a clinically heterogeneous disease that may have atypical presentations with focal cortical syndromes and relatively preserved episodic memory. The posterior variant of AD has two subtypes: occipitotemporal, presenting with visuoperceptive impairment, and biparietal, presenting with visuospatial dysfunction and apraxia. We report a case of a 51-year-old woman with progressive limb apraxia and choreiform movements. Her neuropsychological evaluation was compatible with dementia, and revealed ideomotor and ideational limb apraxia, severe visuoconstructive ability impairment, dyscalculia and posterior aphasia. Workup excluded metabolic, infectious, inflammatory or neoplastic causes, and hereditary conditions as Huntington's disease and familial AD. Cerebrospinal fluid biomarkers revealed ß-amyloid reduction and τ protein increase. Brain imaging showed marked biparietal atrophy and hypoperfusion, and widespread cortical ß-amyloid deposition. Biparietal variant of AD was diagnosed and acetylcholinesterase inhibitor treatment induced clinical stabilisation. AD may present with atypical features and a high clinical suspicion is necessary for an early diagnosis.

Dyscalculia, dysgraphia, and left-right confusion from a left posterior peri-insular infarct.

The Gerstmann syndrome of dyscalculia, dysgraphia, left-right confusion, and finger agnosia is generally attributed to lesions near the angular gyrus of the dominant hemisphere. A 68-year-old right-handed woman presented with sudden difficulty completing a Sudoku grid and was found to have dyscalculia, dysgraphia, and left-right confusion. Magnetic resonance imaging (MRI) showed a focus of abnormal reduced diffusivity in the left posterior insula and temporoparietal operculum consistent with acute infarct. Gerstmann syndrome from an insular or peri-insular lesion has not been described in the literature previously. Pathological and functional imaging studies show connections between left posterior insular region and inferior parietal lobe. We postulate that the insula and operculum lesion disrupted key functional networks resulting in a pseudoparietal presentation.

A twin-case study of developmental number sense impairment.

The current study reports on 9-year-old monozygotic twin girls who fail to make any progress in learning basic mathematics in primary education. We tested the hypothesis that the twins' core maths problems were deficits in number sense that manifested as impairments in approximate and small number systems, resulting in impairment in nonsymbolic as well as in symbolic processing. While age-matched controls (eight typically developing girls) scored highly, the twins scored at chance on all number sense tasks. More specifically, on a nonsymbolic comparison task, even in the simplest ratio condition of 1:2, and on a subitizing task including only numbers under 4, the twins performed at chance and significantly below the same age control group. Responsiveness to an intervention promoting number sense is discussed. As differences between verbal and performance IQ suggest, there seems to be a high degree of specificity in the twins' developmental number sense delays. The concomitant impairments for visual-spatial processing and working memory in the twins might explain the failure to develop number sense.

Arithmetic facts storage deficit: the hypersensitivity-to-interference in memory hypothesis.

Dyscalculia, or mathematics learning disorders, is currently known to be heterogeneous (Wilson & Dehaene, ). While various profiles of dyscalculia coexist, a general and persistent hallmark of this math learning disability is the difficulty in memorizing arithmetic facts (Geary, Hoard & Hamson, ; Jordan & Montani, ; Slade & Russel, ). Arithmetic facts are simple arithmetic problems that are solved by direct retrieval from memory. Recently, De Visscher and Noël () showed hypersensitivity-to-interference in memory in an adult suffering from a specific deficit of arithmetic facts storage. According to the authors, arithmetic facts share many features. The overlapping of these features between arithmetic facts may provoke interference. Consequently, learners who are hypersensitive-to-interference could have considerable difficulties in storing arithmetic facts. The present study aims at testing this new hypothesis on fourth-grade children who are learning multiplication tables. Among 101 children that were assessed, 23 low arithmetic facts learners were selected because of their low score in arithmetic facts fluency (controlling for processing speed). Twenty-three control children were selected, matched for classroom, gender, and age. In addition to a subtest of global reasoning, these participants were given a multiplication production task and a memorization task of low- and high-interference associations. The results show that children with low arithmetic fluencies experience hypersensitivity-to-interference in memory compared with children with typical arithmetic fluencies.

Effects of mental rotation on acalculia: differences in the direction of mental rotation account for the differing characteristics of acalculia induced by right and left hemispheric brain injury.

We observed a 59-year-old right-handed man with an infarction in his right-middle cerebral artery that included the parietal lobe, who abnormally manipulated mental images in the horizontal direction, resulting in calculation disturbances. Three years later, the patient suffered an infarction in the left parietal lobe and displayed abnormalities during the creation of mental images; i.e., he rotated them in the vertical direction, which again resulted in calculation disturbances. These mental imagery disturbances might indicate that a common acalculia mechanism exists between the right and left hemispheres.

At the intersection of math and reading disabilities: introduction to the special issue.

Individuals with comorbid disabilities in mathematics and reading face significant challenges in acquiring the componential skills related to each domain. Persons with these comorbid conditions are significantly understudied and this paucity of work limits how effective practitioners can be at addressing the needs of this population. In the United States, roughly 7% of all children suffer from math disability; of these, an estimated 17% to 66% also has a comorbid reading disability. Underspecification of current conceptualizations of math and reading disabilities, including how to best identify and classify individuals with one or more of these disabilities, hampers our efforts to intervene effectively. To conceptualize how to move forward in these areas, the Eunice Kennedy Shriver National Institute of Child Health and Human Development held a workshop focused on examining the etiology, classification, and remediation of comorbid math and reading disabilities. This special issue, titled At the Intersection of Math and Reading Disabilities, continues that discussion. Contributing authors articulate a path forward to address the needs of these learners and inform the foundational understanding of both conditions in isolation and as they interact.

Gerstmann's syndrome associated with diagnostic cerebral angiography.

OBJECTIVE: Gerstmann's syndrome is a rare neurological disorder characterized by right-left disorientation, finger agnosia, agraphia and acalculia. Several causes for the manifestation of this rare syndrome have been reported in previous publications; however, thus far, an association between secondary diagnostic cerebral angiography and Gerstmann's syndrome has not been reported. CASE REPORT: A 48-year-old woman diagnosed with subarachnoid haemorrhage underwent a secondary diagnostic cerebral angiography 7 months after the episode. The patient showed memory impairment, agraphia, acalculia, right-left disorientation, occasional errors in speech and finger agnosia accompanied by an acute infarction in the left middle cerebral artery territory. However, she showed excellent recovery after intensive rehabilitation and conservative treatment. CONCLUSION: The previously reported rate of permanent neurological complications associated with diagnostic cerebral angiography was very low (0-0.5%). To the best of the authors' knowledge, this is the first case report of Gerstmann's syndrome as a complication of cerebral angiography. This report discusses the complications associated with the neurological condition and emphasizes the need for early rehabilitation in cases of Gerstmann's syndrome.

A case study of arithmetic facts dyscalculia caused by a hypersensitivity-to-interference in memory.

While the heterogeneity of developmental dyscalculia is increasingly recognized, the different profiles have not yet been clearly established. Among the features underpinning types of developmental dyscalculia suggested in the literature, an impairment in arithmetic fact retrieval is particularly prominent. In this paper, we present a case study of an adult woman (DB) with very good cognitive capacities suffering from a specific and developmental arithmetic fact retrieval deficit. We test the main hypotheses about developmental dyscalculia derived from literature. We first explore the influential hypothesis of an approximate number system deficit, through estimation tasks, comparison tasks and a priming comparison task. Secondly, we evaluate whether DB's mathematical deficiencies are caused by a rote verbal memory deficit, using tasks involving completion of expressions, and reciting automatic series such as the alphabet and the months of the year. Alternatively, taking into account the extreme similarity of the arithmetic facts, we propose that a heightened sensitivity to interference could have prevented DB from memorizing the arithmetic facts. The pattern of DB's results on different tasks supports this hypothesis. Our findings identify a new etiology of a specific impairment of arithmetic facts storage, namely a hypersensitivity-to-interference.