Number Form Area Research Articles

Exploring Brain Activation of Single-Digit and Double-digit in Familiar and Unfamiliar Numerals: A Functional MRI Study

The ability to symbolise numbers using numerals is unique to humans and the acquisition of this ability needs to be done via learning [1]. Repeated exposure to sensory input can result in learning-induced alterations to the brain, forming memory engrams that are crucial for memory storage and retrieval [2]. Familiarity is an important factor that affects memory performance because familiar stimuli tend to have stronger memory strength with pre-existing knowledge representation stored in long-term memory, while unfamiliar or novel stimuli do not [1,3]. Past studies have suggested a few putative Number Form Area (NFA), located in the ventral occipitotemporal gyrus, are involved in processing visual number symbols [4 – 6]. It has been put forward that the acquisition of the semantic information of the numerical symbols might be a prerequisite for the activation of the NFA. However, much of its semantic information remains unknown. Figure 1 presented the conceptual framework of the present study.
 
 The present study aims to explore the brain activation associated with familiar and unfamiliar numerals of single-digit and double-digit. The targeted population of the present study will be Malaysian young adults between the age ranges of 18 to 30 years old. The present study will employ a quantitative cross-sectional observational research design. In particular, a within-subjects experimental study design with two factors: type of familiarity (familiar vs. unfamiliar) and the number of digits (single-digit vs. double-digit), will be used to measure the dependent variables including reaction time, accuracy, and brain activations of each participant in all experimental conditions: (1) familiar single-digit, (2) familiar double-digit, (3) unfamiliar single-digit, and (4) unfamiliar double-digit. An fMRI block design paradigm will be utilised, where the participants will be presented with single-digit and double-digit familiar (Chinese) numerals and unfamiliar (Arabic) numerals during the learning (encoding) phase and will be asked to complete the forced-choice memory task during the memory (retrieval) phase. In the experiment, participants’ structural and functional brain images will be collected using 3-Tesla Achieva MRI Scanner (Achieva, Philips, the Netherlands). Behavioural measurements such as reaction time and accuracy of the answer will be recorded based on the responses given by the participants during the fMRI task. Two-way repeated-measures ANOVA tests will be performed to compare the mean difference in reaction time, accuracy, and brain activation between the conditions. The brain activation will undergo pre- and post-processing using Matlab MATLAB software, Statistical Parametric Mapping 12, CONN toolbox and MarsBar toolbox.
 A significantly shorter reaction time and higher accuracy are expected to be observed in familiar as compared to unfamiliar conditions because familiar stimuli are being encountered relatively often in different contexts, which are likely to have broader retrieval contexts and stable mental representation stored in the long-term memory. Besides, it is predicted that brain areas such as the thalamus and the NFA will be highly engaged during the familiar conditions because thalamic nuclei have been reported to underpin familiarity memory [3] and the NFA has been put forward to hold a role in processing meaningful visual numerical symbols [4]. As for unfamiliar condition, the hippocampus and prefrontal cortex (PFC) is predicted to be highly engaged because unfamiliar numerals do not have pre-existing representation stored in the memory, thus it may trigger an active memory encoding process during the learning phase. The retrieval of memory of unfamiliar stimuli at a more recent time point after learning is thought to heavily rely on the hippocampus subregions and the PFC that are highly engaged during the memory encoding process.
 
 In conclusion, significantly better memory performances will be observed with familiar numerals as compared to unfamiliar numeral conditions. Differential neuronal activations will be observed between familiar and unfamiliar numeral conditions.

Children With Dyscalculia Show Hippocampal Hyperactivity During Symbolic Number Perception.

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 (n = 15, mean age: 11.26) and dyscalculia (n = 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.

“Number form area” distinguishes between numerals and other character categories during passive viewing: A meta-synthesis of representational similarity analyses with three studies

“Number form area” distinguishes between numerals and other character categories during passive viewing: A meta-synthesis of representational similarity analyses with three studies

Developmental alterations of the numerical processing networks in the brain

Neuroimaging studies revealed that number perception is mainly located in parietal cortex. Although controversial, it was suggested that number is processed in the frontal lobe in childhood and in the parietal cortex in adulthood. The purpose of this study is to investigate developmental differences in the neural correlates of number representation with fMRI. Sixteen healthy young adults (age:21.69 ± 0.79) and 15 healthy children (age:11.87 ± 0.52) performed a numerosity comparison paradigm which consists of two numerical conditions with two difficulty levels. Adults showed broad parietal cortex activation, as well as activation in the inferior parietal lobes, dorsolateral and medial prefrontal cortex, anterior and posterior cingulate cortex, and peristriate cortex (PC) during number processing. Children showed activations in the intraparietal sulcus and PC. Group differences were observed in the posterior insula, fusiform gyrus, and PC whose coordinates correspond to the number form area (NFA). Region of interest analysis was performed for these clusters to get the time series of hemodynamic responses which were estimated with a finite impulse response function. In contrast to the prominent frontoparietal shift theory, no age-related differences were observed in the frontoparietal regions. Overall, the presented study suggests developmental changes in the brain’s number processing revolving around the NFA.

Investigating the visual number form area: a replication study.

The influential triple-code model of number representation proposed that there are three distinct brain regions for three different numerical representations: verbal words, visual digits and abstract magnitudes. It was hypothesized that the region for visual digits, known as the number form area, would be in ventral occipitotemporal cortex (vOTC), near other visual category-specific regions, such as the visual word form area. However, neuroimaging investigations searching for a region that responds in a category-specific manner to the visual presentation of number symbols have yielded inconsistent results. Price & Ansari (Price, Ansari 2011 Neuroimage 57, 1205–1211) investigated whether any regions activated more in response to passively viewing digits in contrast with letters and visually similar nonsense symbols and identified a region in the left angular gyrus. By contrast, Grotheer et al. (Grotheer, Herrmann, Kovács 2016 J. Neurosci. 36, 88–97) found bilateral regions in vOTC which were more activated in response to digits than other stimuli categories while performing a one-back task. In the current study, we aimed to replicate the findings reported in Grotheer et al. with Price & Ansari's passive viewing task as this is the most stringent test of bottom-up, sensory-driven, category-specific perception. Moreover, we used the contrasts reported in both papers in order to test whether the discrepancy in findings could be attributed to the difference in analysis.

Connectivity of the Human Number Form Area Reveals Development of a Cortical Network for Mathematics.

The adult brain contains cortical areas thought to be specialized for the analysis of numbers (the putative number form area, NFA) and letters (the visual word form area, VWFA). Although functional development of the VWFA has been investigated, it is largely unknown when and how the NFA becomes specialized and connected to the rest of the brain. One hypothesis is that NFA and VWFA derive their special functions through differential connectivity, but the development of this differential connectivity has not been shown. Here, we mapped the resting state connectivity of NFA and VWFA to the rest of the brain in a large sample (n = 437) of individuals (age 3.2–21 years). We show that within NFA-math network and within VWFA-reading network the strength of connectivity increases with age. The right NFA is significantly connected to the right intraparietal cortex already at the earliest age tested (age 3), before formal mathematical education has begun. This connection might support or enable an early understanding of magnitude or numerosity In contrast, the functional connectivity from NFA to the left anterior intraparietal cortex and to the right dorsolateral prefrontal cortex is not different from the functional connectivity of VWFA to these regions until around 12–14 years of age. The increase in connectivity to these regions was associated with a gradual increase in mathematical ability in an independent sample. In contrast, VWFA connects significantly to Broca’s region around age 6, and this connectivity is correlated with reading ability. These results show how the differential connectivity of the networks for mathematics and reading slowly emerges through years of training and education.

Neurocognitive mechanisms of digit processing and their relationship with mathematics competence

The dominant model of number processing suggests the existence of a Number Form Area (NFA) in the inferior temporal gyrus (ITG) that supports the processing of Arabic digits as visual symbols of number. However, studies have produced inconsistent evidence for the presence and laterality of digit-specific ITG activity. Furthermore, whether any such activity relates to mathematical competence is unknown. This study investigated these two issues using functional magnetic resonance imaging. Thirty-two adults performed digit and letter detection tasks and reading and mathematics tests. During digit detection, participants determined whether digits were present in a string of letters (e.g., AH3NR versus AHTNR). During letter detection, participants determined whether letters were present in a string of digits (e.g., 93R78 versus 93478). Results showed four clusters in frontal, occipital, and temporal regions for digit detection, including a left ITG cluster. Five clusters in frontal, parietal, occipital, and temporal regions were associated with letter detection, including a left ITG cluster. Digit and letter-related ITG clusters were spatially distinct; however, a direct contrast of digit and letter processing did not reveal greater activity in the left ITG for digit detection. Whole brain correlations showed greater digit-related activity in the right ITG for participants with higher calculation skills, but there was no correlation between letter activity and calculation skills. Together, our results suggest functional localization, but not specialization, for digits in the left ITG and provide the first evidence of a relationship between calculation skills and digit processing in the right ITG.

Neuronal Population Responses in the Human Ventral Temporal and Lateral Parietal Cortex during Arithmetic Processing with Digits and Number Words.

Past research has identified anatomically specific sites within the posterior inferior temporal gyrus (PITG) and the intraparietal sulcus (IPS) areas that are engaged during arithmetic processing. Although a small region of the PITG (known as the number form area) is selectively engaged in the processing of numerals, its surrounding area is activated during both digit and number word processing. In eight participants with intracranial electrodes, we compared the timing and selectivity of electrophysiological responses in the number form area-surround and IPS regions during arithmetic processing with digits and number words. Our recordings revealed stronger electrophysiological responses in the high-frequency broadband range in both regions to digits than number words, with the difference that number words elicited delayed activity in the IPS but not PITG. Our findings of distinct profiles of responses in the PITG and the IPS to digits compared with number words provide novel information that is relevant to existing theoretical models of mathematical cognition.

A preference for mathematical processing outweighs the selectivity for Arabic numbers in the inferior temporal gyrus

A region in the posterior inferior temporal gyrus (ITG), referred to as the number form area (NFA, here ITG-numbers) has been implicated in the visual processing of Arabic numbers. However, it is unknown if this region is specifically involved in the visual encoding of Arabic numbers per se or in mathematical processing more broadly. Using functional magnetic resonance imaging (fMRI) during experiments that systematically vary tasks and stimuli, we find that mathematical processing, not preference to Arabic numbers, consistently drives both mean and distributed responses in the posterior ITG. While we replicated findings of higher responses in ITG-numbers to numbers than other visual stimuli during a 1-back task, this preference to numbers was abolished when participants engaged in mathematical processing. In contrast, an ITG region (ITG-math) that showed higher responses during an adding task vs. other tasks maintained this preference for mathematical processing across a wide range of stimuli including numbers, number/letter morphs, hands, and dice. Analysis of distributed responses across an anatomically-defined posterior ITG expanse further revealed that mathematical task but not Arabic number form can be successfully and consistently decoded from these distributed responses. Together, our findings suggest that the function of neuronal regions in the posterior ITG goes beyond the specific visual processing of Arabic numbers. We hypothesize that they ascribe numerical content to the visual input, irrespective of the format of the stimulus.

Exploring the Origins and Development of the Visual Number Form Area: A Functionally Specialized and Domain-Specific Region for the Processing of Number Symbols?

The existence of a region of cortex in the ventral visual stream that responds selectively to visual presentation of numerical symbols was first postulated in the triple-code model of number processing ([Dehaene, 1992][1]). This theory proposed that there are separate neural codes dedicated to

Causal evidence of the involvement of the number form area in the visual detection of numbers and letters

Recent research suggests the existence of a visual area selectively processing numbers in the human inferior temporal cortex (number form area (NFA); Abboud et al., 2015; Grotheer et al., 2016; Shum et al., 2013). The NFA is thought to be involved in the preferential encoding of numbers over false characters, letters and non-number words (Grotheer et al., 2016; Shum et al., 2013), independently of the sensory modality (Abboud et al., 2015). However, it is not yet clear if this area is mandatory for normal number processing. The present study exploited the fact that high-resolution fMRI can be applied to identify the NFA individually (Grotheer et al., 2016) and tested if transcranial magnetic stimulation (TMS) of this area interferes with stimulus processing in a selective manner. Double-pulse TMS targeted at the right NFA significantly impaired the detection of briefly presented and masked Arabic numbers in comparison to vertex stimulation. This suggests the NFA to be necessary for fluent number processing. Surprisingly, TMS of the NFA also impaired the detection of Roman letters. On the other hand, stimulation of the lateral occipital complex (LO) had neither an effect on the detection of numbers nor on letters. Our results show, for the first time, that the NFA is causally involved in the early visual processing of numbers as well as of letters.

Neuroimaging Evidence of a Bilateral Representation for Visually Presented Numbers.

This fMRI study shows for the first time a cluster of neurons selective for visually presented numbers in healthy human adults. This visual number form area (NFA) was found in both hemispheres. Crucially, numbers have gained importance for humans too recently for neuronal specialization to be established by evolution. Therefore, investigations of this region will greatly advance our understanding of learning and plasticity in the brain. In addition, these results will aid our knowledge regarding related neurological illnesses (e.g., dyscalculia). To overcome the fMRI signal dropout in the neighborhood of the NFA, we combined high spatial resolution with liberal smoothing. We believe that this approach will be useful to the broad neuroimaging community.

A number-form area in the blind

Distinct preference for visual number symbols was recently discovered in the human right inferior temporal gyrus (rITG). It remains unclear how this preference emerges, what is the contribution of shape biases to its formation and whether visual processing underlies it. Here we use congenital blindness as a model for brain development without visual experience. During fMRI, we present blind subjects with shapes encoded using a novel visual-to-music sensory-substitution device (The EyeMusic). Greater activation is observed in the rITG when subjects process symbols as numbers compared with control tasks on the same symbols. Using resting-state fMRI in the blind and sighted, we further show that the areas with preference for numerals and letters exhibit distinct patterns of functional connectivity with quantity and language-processing areas, respectively. Our findings suggest that specificity in the ventral ‘visual’ stream can emerge independently of sensory modality and visual experience, under the influence of distinct connectivity patterns.

Symbol processing in the left angular gyrus: Evidence from passive perception of digits

Arabic digits are one of the most ubiquitous symbol sets in the world. While there have been many investigations into the neural processing of the semantic information digits represent (e.g. through numerical comparison tasks), little is known about the neural mechanisms which support the processing of digits as visual symbols. To characterise the component neurocognitive mechanisms which underlie numerical cognition, it is essential to understand the processing of digits as a visual category, independent of numerical magnitude processing. The 'Triple Code Model' (Dehaene, 1992; Dehaene and Cohen, 1995) posits an asemantic visual code for processing Arabic digits in the ventral visual stream, yet there is currently little empirical evidence in support of this code. This outstanding question was addressed in the current functional Magnetic Resonance (fMRI) study by contrasting brain responses during the passive viewing of digits versus letters and novel symbols at short (50 ms) and long (500 ms) presentation times. The results of this study reveal increased activation for familiar symbols (digits and letters) relative to unfamiliar symbols (scrambled digits and letters) at long presentation durations in the left dorsal Angular gyrus (dAG). Furthermore, increased activation for Arabic digits was observed in the left ventral Angular gyrus (vAG) in comparison to letters, scrambled digits and scrambled letters at long presentation durations, but no digit specific activation in any region at short presentation durations. These results suggest an absence of a digit specific 'Visual Number Form Area' (VNFA) in the ventral visual cortex, and provide evidence for the role of the left ventral AG during the processing of digits in the absence of any explicit processing demands. We conclude that Arabic digit processing depends specifically on the left AG rather than a ventral visual stream VNFA.