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.

Control over sampling boosts numerical evidence processing in human decisions from experience.

When acquiring information about choice alternatives, decision makers may have varying levels of control over which and how much information they sample before making a choice. How does control over information acquisition affect the quality of sample-based decisions? Here, combining variants of a numerical sampling task with neural recordings, we show that control over when to stop sampling can enhance (i) behavioral choice accuracy, (ii) the build-up of parietal decision signals, and (iii) the encoding of numerical sample information in multivariate electroencephalogram patterns. None of these effects were observed when participants could only control which alternatives to sample, but not when to stop sampling. Furthermore, levels of control had no effect on early sensory signals or on the extent to which sample information leaked from memory. The results indicate that freedom to stop sampling can amplify decisional evidence processing from the outset of information acquisition and lead to more accurate choices.

Phonological activation improves semantic access provided by Arabic digits and number words.

Arabic digits (e.g., "6") and number words (e.g., "", "six", " ") are the two main formats in which numbers can be represented. Although phonology plays a crucial role in the semantic accessing of alphabetic words and Chinese characters, whether it is involved in the processing of different numerical notations, which have been shown to be dissociable from characters, is still unknown. Using a parity judgment task, two experiments were performed by manipulating the phonological relationship between a prime and a target. The primes were Tibetan or Chinese characters and the targets were presented either as number words (Experiment 1) or as Arabic digits (Experiment 2). The results revealed that phonology affected semantic access for both number words and Arabic digits. Additionally, semantic access for Tibetan number words was more susceptible to phonological information. The results for Arabic digits followed the same pattern for Tibetan primes. Further, language proficiency also affected the role of phonology in number processing. Participants with low language proficiency relied more on phonological encoding when processing the numbers. The results suggest that phonology is crucial for semantic access of different numerical notations.

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.

Magnitude comparison and automaticity in number processing in adolescents with prenatal alcohol exposure: An event-related potentials study.

BACKGROUND: Individuals with fetal alcohol spectrum disorders may exhibit a distinct pattern of dysmorphic facial features, growth restriction, and cognitive deficits, particularly in arithmetic. Magnitude comparison, a fundamental element of numerical cognition, is modulated by the numerical distance effect, with numbers closer in value more difficult to compare than those further apart, and by the automaticity of the association of numerical values with their symbolic representations (Arabic numerals). METHODS: We examined event-related potentials acquired during the Numerical Stroop numerical and physical tasks administered to 24 alcohol-exposed adolescents (eight fetal alcohol syndrome (FAS), eight partial FAS (PFAS), eight heavily exposed (HE) nonsyndromal) and 23 typically developing (TD), same- age controls. The distance effect was assessed on the numerical task to examine differences in reaction time (RT) and accuracy when two numbers are close in value (e.g., 1 vs. 2) compared to when the numbers are less close (e.g., 1 vs. 6). Automaticity was assessed in the physical task by examining the degree to which RT and accuracy are reduced when the relative physical size of two numerals is incongruent with their numerical values (e.g., 1 vs. 6). RESULTS: Adolescents in all four groups performed behaviorally as expected on these relatively simple magnitude comparison tasks, but accuracy was poorer and RT was slower on both tasks in the FAS and PFAS than the HE and TD groups. At the neurophysiological level, in the numerical task, a higher level of prenatal alcohol exposure was associated with smaller P2p amplitude. In the physical task, only the TD and nonsyndromal HE groups exhibited the expected smaller P300 amplitude in the incongruent than the congruent condition. CONCLUSIONS: These findings suggest that magnitude comparison in alcohol-exposed individuals may be mediated by recruitment of alternative neural pathways that are likely to be inefficient when number processing becomes more challenging.

Transcoding counts: Longitudinal contribution of number writing to arithmetic in different languages.

Number writing involves transcoding from number words (e.g., "thirty-two") to written digit strings (32) and is an important unique predictor of arithmetic. The existing longitudinal evidence about the relation between transcoding and arithmetic is mostly language specific. In languages with number word inversion (e.g., German), the order of tens and units is transposed in spoken number words compared with Arabic numbers. This makes transcoding more challenging than in languages without number word inversion (e.g., English). In the current study, we aimed to understand whether the contribution of number writing to the development of arithmetic is similar in languages with and without number word inversion. German-speaking children (n = 166) and English-speaking children (n = 201) were followed over the first 3 years of primary school. In a series of multiple linear regressions, we tested whether number writing of multi-digit numbers was a significant unique predictor of arithmetic after controlling for well-known non-numerical predictors (nonverbal reasoning and working memory) and numerical predictors (symbolic and nonsymbolic magnitude comparison). Number writing in Grade 1 predicted arithmetic in Grades 1, 2, and 3 over and above the other predictors. Crucially, number writing performance was of comparable importance for arithmetic development in German- and English-speaking children. Our findings extend previous evidence by showing that transcoding predicts the development of arithmetic skills during the first 3 years of primary school in languages with and without number word inversion.

Cognitive control in number processing: new evidence from number compatibility effects in task-switching.

A growing body of research suggests that basic numerical abilities such as number magnitude processing are influenced by cognitive control processes. So far, evidence for number processing being affected by cognitive control processes stems primarily from observed adaptations of numerical effects to stimulus set characteristics (e.g. order or ratio of specific stimulus types). Complementing previous research on adaptation to stimulus set characteristics as an index of influences of cognitive control, the present study employed a task-switching paradigm to examine how cognitive control processes influence number processing. Participants were presented with a two-digit number and had to either judge its parity or compare its magnitude to a standard depending on a preceding cue. We expected numerical congruency effects (i.e. the unit-decade compatibility effect for magnitude comparisons and the parity congruity effect for parity judgements) to be larger in switch trials, as persisting activation of the task set of the preceding trial should increase interference. In contrast to our expectations, both numerical congruity effects were reduced following task switches as compared to repetitions. This interaction of task-switching with numerical congruency effects suggests an influence of cognitive control on basic number processing in form of persisting inhibition of previously abandoned task sets, so that these exert less influence on current number processing demands.

How does working memory matter in young children's arithmetic skills: The mediating role of basic number processing.

The current study investigated whether and how each component of the working memory model was associated with kindergarten children's arithmetic performance. A total of 103 Chinese kindergarten children were administered tests of the visuospatial sketchpad, the phonological loop, the central executive, and basic number processing (i.e., number line estimation, nonverbal numerosity estimation and numerical magnitude comparison). The results showed that among the three working memory components, the central executive accounted for a significant proportion of the variance in young children's arithmetic performance. In terms of basic number processing, number line estimation and numerical magnitude comparison had significant influences on young children's arithmetic performance. Furthermore, numerical magnitude comparison played a mediating role between the visuospatial sketchpad and early arithmetic skills. These findings highlight the importance of working memory and basic number processing in early arithmetic skills and reveal different pathways through which the three working memory components influence young children's arithmetic performance.

Deficits in or preservation of basic number processing in Parkinson's disease? A registered report.

Neurodegenerative diseases such as Parkinson's disease (PD) have a huge impact on patients, caregivers, and the health-care system. To date, the diagnosis of mild cognitive impairments in PD has been established based on domain-general functions such as executive functions, attention, or working memory. However, specific numerical deficits observed in clinical practice have not yet been systematically investigated. PD-immanent deterioration of domain-general functions and domain-specific numerical areas suggests the mechanisms of both primary and secondary dyscalculia. The current study will systematically investigate basic number processing performance in PD patients for the first time, targeting domain-specific cognitive representations of numerosity and the influence of domain-general factors. The overall sample consists of patients with a diagnosis of PD, according to consensus guidelines, and healthy controls. PD patients will be stratified into patients with normal cognition or mild cognitive impairment (level I-PD-MCI based on cognitive screening). Basic number processing will be assessed using transcoding, number line estimation, and (non)symbolic number magnitude comparison tasks. Discriminant analysis will be employed to assess whether basic number processing tasks can differentiate between a healthy control group and both PD groups. All participants will be subjected to a comprehensive numerical and a neuropsychological test battery, as well as sociodemographic and clinical measures. Study results will give the first broad insight into the extent of basic numerical deficits in different PD patient groups and will help us to understand the underlying mechanisms of the numerical deficits faced by PD patients in daily life.

Mapping subcomponents of numerical cognition in relation to functional and anatomical landmarks of human parietal cortex.

Human functional imaging has identified the middle part of the intraparietal sulcus (IPS) as an important brain substrate for different types of numerical tasks. This area is often equated with the macaque ventral intraparietal area (VIP) where neuronal selectivity for non-symbolic numerical stimuli (sets of items) is found. However, the low spatial resolution and whole-brain averaging analysis performed in most fMRI studies limit the extent to which an exact correspondence of activations in different numerical tasks with specific sub-regions of the IPS can be established. Here we acquired high-resolution 7T fMRI data in a group of human adults and related the activations in several numerical contrasts (implying different numerical stimuli and tasks) to anatomical and functional landmarks on the cortical surface. Our results reveal a functional heterogeneity within human intraparietal cortex where the retinotopic visual field maps in superior/medial parts of the IPS and superior parietal gyrus respond preferentially to the visual processing of concrete sets of items (over single Arabic numerals), whereas lateral/inferior parts of the IPS are predominantly recruited during numerical operations such as calculation and quantitative comparison. Since calculation and comparison-related activity fell mainly outside the retinotopic visual field maps considered the human functional equivalent of the monkey VIP/LIP complex, the areas most activated during such numerical operations in humans are likely different from VIP.

Distinct neural mechanisms for reading Arabic vs. verbal numbers: An ERP study.

In this electroencephalogram/event-related potential (EEG/ERP) study, 16 volunteers were asked to compare the numerical equality of 360 pairs of multidigit numbers presented in Arabic or verbal format. Behavioural data showed faster and more accurate responses for digit targets, with a right hand/left hemisphere advantage only for verbal numerals. Occipito-temporal N1, peaking at approximately 180 ms, was strongly left-lateralized during verbal number processing and bilateral during digit processing. A LORETA (low-resolution electromagnetic tomography) source reconstruction performed at the N1 latency stage (155-185 ms) revealed greater brain activation during coding of Arabic than of verbal stimuli. Digit perceptual coding was associated with the activation of the right angular gyrus (rAG), the left fusiform gyrus (FG,BA37), and left and right superior and medial frontal areas. N1 sources for verbal numerals included the left FG (BA37), the precuneus (BA31), the parahippocampal area and a small right prefrontal activation. In addition, verbal numerals elicited a late frontocentral negativity, possibly reflecting stimulus unfamiliarity or complexity. Overall, the data suggest distinct mechanisms for number reading through ciphers (digits) or words. Information about quantity was accessed earlier and more accurately if numbers were in a nonlinguistic code. Indeed, it can be speculated that numerosity processing would involve circuits originally involved in processing space (i.e., rAG/rIPS).

Investigating the respective contribution of sensory modalities and spatial disposition in numerical training.

Recent studies have suggested that multisensory redundancy may improve cognitive learning. According to this view, information simultaneously available across two or more modalities is highly salient and, therefore, may be learned and remembered better than the same information presented to only one modality. In the current study, we wanted to evaluate whether training arithmetic with a multisensory intervention could induce larger learning improvements than a visual intervention alone. Moreover, because a left-to-right-oriented mental number line was for a long time considered as a core feature of numerical representation, we also wanted to compare left-to-right-organized and randomly organized arithmetic training. Therefore, five training programs were created and called (a) multisensory linear, (b) multisensory random, (c) visual linear, (d) visual random, and (e) control. A total of 85 preschoolers were randomly assigned to one of these five training conditions. Whereas children were trained to solve simple addition and subtraction operations in the first four training conditions, story understanding was the focus of the control training. Several numerical tasks (arithmetic, number-to-position, number comparison, counting, and subitizing) were used as pre- and post-test measures. Although the effect of spatial disposition was not significant, results demonstrated that the multisensory training condition led to a significantly larger performance improvement than the visual training and control conditions. This result was specific to the trained ability (arithmetic) and is discussed in light of the multisensory redundancy hypothesis.

Symbolic fractions elicit an analog magnitude representation in school-age children.

A fundamental question about fractions is whether they are grounded in an abstract nonsymbolic magnitude code similar to that postulated for whole numbers. Mounting evidence suggests that symbolic fractions could be grounded in mechanisms for perceiving nonsymbolic ratio magnitudes. However, systematic examination of such mechanisms in children has been lacking. We asked second- and fifth-grade children (prior to and after formal instructions with fractions, respectively) to compare pairs of symbolic fractions, nonsymbolic ratios, and mixed symbolic-nonsymbolic pairs. This paradigm allowed us to test three key questions: (a) whether children show an analog magnitude code for rational numbers, (b) whether that code is compatible with mental representations of symbolic fractions, and (c) how formal education with fractions affects the symbolic-nonsymbolic relation. We examined distance effects as a marker of analog ratio magnitude processing and notation effects as a marker of converting across numerical codes. Second and fifth graders' reaction times and error rates showed classic distance and notation effects. Nonsymbolic ratios were processed most efficiently, with mixed and symbolic notations being relatively slower. Children with more formal instruction in symbolic fractions had a significant advantage in comparing symbolic fractions but had a smaller advantage for nonsymbolic ratio stimuli. Supplemental analyses showed that second graders relied on numerator distance more than holistic distance and that fifth graders relied on holistic fraction magnitude distance more than numerator distance. These results suggest that children have a nonsymbolic ratio magnitude code and that symbolic fractions can be translated into that magnitude code.

Further insights into the operation of the Chinese number system: Competing effects of Arabic and Mandarin number formats.

Here we report the results of a speeded relative quantity task with Chinese participants. On each trial a single numeral (the probe) was presented and the instructions were to respond as to whether it signified a quantity less than or greater than five (the standard). In separate blocks of trials, the numerals were presented either in Mandarin or in Arabic number formats. In addition to the standard influence of numerical distance, a significant predictor of performance was the degree of physical similarity between the probe and the standard as depicted in Mandarin. Additionally, competing effects of physical similarity, defined in terms of the Arabic number format, were also found. Critically the size of these different effects of physical similarity varied systematically across individuals such that larger effects of one compensated for smaller effects of the other. It is argued that the data favor accounts of processing that assume that different number formats access different format-specific representations of quantities. Moreover, for Chinese participants the default is to translate numerals into a Mandarin format prior to accessing quantity information. The efficacy of this translation process is itself influenced by a competing tendency to carry out a translation into Arabic format.

Semantic associations between arithmetic and space: Evidence from temporal order judgements.

Spatial biases associated with subtraction or addition problem solving are generally considered as reflecting leftward or rightward attention shifts along a mental numerical continuum, but an alternative hypothesis not implying spatial attention proposes that the operator (plus or minus sign) may favour a response to one side of space (left or right) because of semantic associations. We tested these two accounts in a series of temporal order judgement experiments that consisted in the auditory presentation of addition or subtraction problems followed 200 ms (Experiments 1-2) or 800 ms (Experiment 3) later by the display of two lateralized targets in close temporal succession. To dissociate the side where the operation first brought their attention from the side they had to respond to, we asked participants to report which of the left or right target appeared first or last on screen. Under the attention-orienting account, addition should elicit more rightward responses than subtraction when participants have to focus on the first target, but more leftward responses when they have to focus on the last target, because the latter is opposite to the side where the operation first brought their attention. Under the semantic account, addition should elicit more rightward responses than subtraction, no matter the focus is on the first or last target, because participants should systematically favour the side conceptually linked to the operator. The results of the three experiments converge to indicate that, in lateralized target detection tasks, the spatial biases induced by arithmetic operations stem from semantic associations.

Neuro-cognitive mechanisms of global Gestalt perception in visual quantification.

Recent neuroimaging studies identified posterior regions in the temporal and parietal lobes as neuro-functional correlates of subitizing and global Gestalt perception. Beyond notable overlap on a neuronal level both mechanisms are remarkably similar on a behavioral level representing both a specific form of visual top-down processing where single elements are integrated into a superordinate entity. In the present study, we investigated whether subitizing draws on principles of global Gestalt perception enabling rapid top-down processes of visual quantification. We designed two functional neuroimaging experiments: a task identifying voxels responding to global Gestalt stimuli in posterior temporo-parietal brain regions and a visual quantification task on dot patterns with magnitudes within and outside the subitizing range. We hypothesized that voxels activated in global Gestalt perception should respond stronger to dot patterns within than those outside the subitizing range. The results confirmed this prediction for left-hemispheric posterior temporo-parietal brain areas. Additionally, we trained a classifier with response patterns from global Gestalt perception to predict neural responses of visual quantification. With this approach we were able to classify from TPJ Gestalt ROIs of both hemispheres whether a trial requiring subitizing was processed. The present study demonstrates that mechanisms of subitizing seem to build on processes of high-level visual perception.

The neural circuits of number and letter copying: an fNIRS study.

In our daily lives, we are constantly exposed to numbers and letters. However, it is still under debate how letters and numbers are processed in the brain, while information on this topic would allow for a more comprehensive understanding of, for example, known influences of language on numerical cognition or neural circuits shared by numerical cognition and language processing. Some findings provide evidence for a double dissociation between numbers and letters, with numbers being represented in the right and letters in the left hemisphere, while the opposing view suggests a shared neural network. Since processing may depend on the task, we address the reported inconsistencies in a very basic symbol copying task using functional near-infrared spectroscopy (fNIRS). fNIRS data revealed that both number and letter copying rely on the bilateral middle and left inferior frontal gyri. Only numbers elicited additional activation in the bilateral parietal cortex and in the left superior temporal gyrus. However, no cortical activation difference was observed between copying numbers and letters, and there was Bayesian evidence for common activation in the middle frontal gyri and superior parietal lobules. Therefore, we conclude that basic number and letter processing are based on a largely shared cortical network, at least in a simple task such as copying symbols. This suggests that copying can be used as a control condition for more complex tasks in neuroimaging studies without subtracting stimuli-specific activation.

Electrophysiological Responses in the Ventral Temporal Cortex During Reading of Numerals and Calculation.

Recent evidence suggests that specific neuronal populations in the ventral temporal cortex show larger electrophysiological responses to visual numerals compared with morphologically similar stimuli. This study investigates how these responses change from simple reading of numerals to the active use of numerals in an arithmetic context. We recorded high-frequency broadband (HFB) signals, a reliable measure for local neuronal population activity, while 10 epilepsy patients implanted with subdural electrodes performed separate numeral reading and calculation tasks. We found that calculation increased activity in the posterior inferior temporal gyrus (ITG) with a factor of approximately 1.5 over the first 500 ms of calculation, whereas no such increase was noted for reading numerals without calculation or reading and judging memory statements. In a second experiment conducted in 2 of the same subjects, we show that HFB responses increase in a systematic manner when the single numerals were presented successively in a calculation context: The HFB response in the ITG, to the second and third numerals (i.e., b and c in a + b = c), was approximately 1.5 times larger than the responses to the first numeral (a). These results provide electrophysiological evidence for modulation of local neuronal population responses to visual stimuli based on increasing task demands.

Cognitive mechanisms underlying third graders' arithmetic skills: Expanding the pathways to mathematics model.

A modified pathways to mathematics model was used to examine the cognitive mechanisms underlying arithmetic skills in third graders. A total of 269 children were assessed on tasks tapping the four pathways and arithmetic skills. A path analysis showed that symbolic number processing was directly supported by the linguistic and approximate quantitative pathways. The direct contribution from the four pathways to arithmetic proficiency varied; the linguistic pathway supported single-digit arithmetic and word problem solving, whereas the approximate quantitative pathway supported only multi-digit calculation. The spatial processing and verbal working memory pathways supported only arithmetic word problem solving. The notion of hierarchical levels of arithmetic was supported by the results, and the different levels were supported by different constellations of pathways. However, the strongest support to the hierarchical levels of arithmetic were provided by the proximal arithmetic skills.

How do individual differences in children's domain specific and domain general abilities relate to brain activity within the intraparietal sulcus during arithmetic? An fMRI study.

Previous research has demonstrated that children recruit the intraparietal sulcus (IPS) during arithmetic, which has largely been attributed to domain-specific processes such as quantity manipulations. However, the IPS has also been found to be important for domain-general abilities, such as visuo-spatial working memory (VSWM). Based on the current literature it is unclear whether individual differences in domain-specific skills, domain-general skills, or a combination of the two, are related to the recruitment of the IPS during arithmetic. This study examines how individual differences in both domain general and domain specific competencies relate to brain activity in the IPS during arithmetic, and whether the relationships are related to how brain activity is measured. In a sample of 44 school-aged children, we found that VSWM was only weakly related to a neural index of arithmetic complexity (neural problem size effect), whereas symbolic number processing skills (symbolic comparison and ordering) were related to overall arithmetic activity (both small and large problems). By simultaneously examining multiple domain-general and domain specific measures, we were also able to determine that symbolic skills were a stronger predictor of brain activity within the IPS than domain general skills such as VSWM and domain specific skills such as non-symbolic number processing. Together, these findings highlight that neural problem size effect may reflect different cognitive processes than brain activity across both small and large arithmetic problems, and that symbolic number processing skills are a critical predictor of variability in IPS activity during arithmetic. Hum Brain Mapp 38:3941-3956, 2017. © 2017 Wiley Periodicals, Inc.