Alterations in functional brain connectivity associated with developmental dyscalculia.

BACKGROUND AND PURPOSE: In recent years, there has been a growing interest in the study of resting neural networks in different neurological and mental disorders. While previous studies suggest that the default mode network (DMN) may be altered in dyscalculia, the study of resting-state networks in the development of numerical skills, especially in children with developmental dyscalculia (DD), is scarce and relatively recent. Based on this, this study examines differences in resting-state functional connectivity (rs-FC) data of children with DD using functional connectivity multivariate pattern analysis (fc-MVPA), a data-driven methodology that summarizes properties of the entire connectome. METHODS: We performed fc-MVPA on resting-state images of a sample composed of a group of children with DD (n = 19, 8.06 ± 0.87 years) and an age- and sex-matched control group of typically developing children (n = 23, 7.76 ± 0.46 years). RESULTS: Analysis of fc-MVPA showed significant differences between group connectivity profiles in two clusters allocated in both the right and left medial temporal gyrus. Post hoc effect size results revealed a decreased rs-FC between each temporal pole and the DMN in children with DD and an increased rs-FC between each temporal pole and the sensorimotor network. CONCLUSIONS: Our results suggest an aberrant information flow between resting-state networks in children with DD, demonstrating the importance of these networks for arithmetic development.

Improving Reading Skills Using a Computerized Phonological Training Program in Early Readers with Reading Difficulties.

In the last years, there has been a big effort to identify risk factors for reading difficulties and to develop new methodologies to help struggling readers. It has been shown that early intervention is more successful than late intervention, and that intensive training programs can benefit children with reading difficulties. The aim of our study is to investigate the effectiveness of an intensive computerized phonological training program designed to improve reading performance in a sample of children with reading difficulties at the early stages of their reading learning process. Thirty-two children with reading difficulties were randomly assigned to one of the two intervention groups: RDIR (children with reading difficulties following a computerized intensive remediation strategy) (n = 20) (7.01 ± 0.69 years), focused on training phonemic awareness, decoding and reading fluency through the computational training; and RDOR (children with reading difficulties following an ordinary remediation strategy) (n = 12) (6.92 ± 0.82 years), which consisted of a reinforcement of reading with a traditional training approach at school. Normal readers (NR) were assigned to the control group (n = 24) (7.32 ± 0.66 years). Our results indicate that both the RDIR and RDOR groups showed an increased reading performance after the intervention. However, children in the RDIR group showed a stronger benefit than the children in the RDOR group, whose improvement was weaker. The control group did not show significant changes in reading performance during the same period. In conclusion, results suggest that intensive early intervention based on phonics training is an effective strategy to remediate reading difficulties, and that it can be used at school as the first approach to tackle such difficulties.

Use of transcranial magnetic stimulation for studying the neural basis of numerical cognition: A systematic review.

Complex numerical cognition is a crucial ability in the human brain. Conventional neuroimaging techniques do not differentiate between epiphenomena and neuronal groups critical to numerical cognition. Transcranial magnetic stimulation (TMS) allows defining causal models of the relationships between specific activated or inhibited neural regions and functional changes in cognition. However, there is insufficient knowledge on the differential effects of various TMS protocols and stimulation parameters on numerical cognition. This systematic review aimed to synthesize the evidence that different TMS protocols provide regarding the neural basis of numerical cognition in healthy adults. We included 21 experimental studies in which participants underwent any transcranial magnetic stimulation such as a single pulse TMS, repetitive TMS, and theta-burst stimulation. The primary outcome measures were any change in numerical cognition processes evidenced by numerical or magnitude tasks, measured with any independent variable like reaction times, accuracy, or congruency effects. TMS applied to regions of the parietal cortex and prefrontal cortex has neuromodulatory effects, which translate into measurable behavioral effects affecting cognitive functions related to arithmetic and numerical and magnitude processing. The use of TMS for the study of the neural bases of numerical cognition allows addressing issues such as localization, timing, lateralization and has allowed establishing site-function dissociations and double site-function dissociations. Moreover, this technique is in a moment of expansion due to the growing knowledge of its physiological effects and the enormous potential of combining TMS with other techniques such as electroencephalography, functional magnetic resonance imaging, or near-infrared spectroscopy to reach a more precise brain mapping.

Functional connectivity alterations associated with literacy difficulties in early readers.

The link between literacy difficulties and brain alterations has been described in depth. Resting-state fMRI (rs-fMRI) has been successfully applied to the study of intrinsic functional connectivity (iFc) both in dyslexia and typically developing children. Most related studies have focused on the stages from late childhood into adulthood using a seed to voxel approach. Our study analyzes iFc in an early childhood sample using the multivariate pattern analysis. This facilitates a hypothesis-free analysis and the possible identification of abnormal functional connectivity patterns at a whole brain level. Thirty-four children with literacy difficulties (LD) (7.1 ± 0.69 yr.) and 30 typically developing children (TD) (7.43 ± 0.52 yr.) were selected. Functional brain connectivity was measured using an rs-fMRI acquisition. The LD group showed a higher iFc between the right middle frontal gyrus (rMFG) and the default mode network (DMN) regions, and a lower iFc between the rMFG and both the bilateral insular cortex and the supramarginal gyrus. These results are interpreted as a DMN on/off routine malfunction in the LD group, which suggests an alteration of the task control network regulating DMN activity. In the LD group, the posterior cingulate cortex also showed a lower iFc with both the middle temporal poles and the fusiform gyrus. This could be interpreted as a failure in the integration of information between brain regions that facilitate reading. Our results show that children with literacy difficulties have an altered functional connectivity in their reading and attentional networks at the beginning of the literacy acquisition. Future studies should evaluate whether or not these alterations could indicate a risk of developing dyslexia.

Glucose and caffeine effects on sustained attention: an exploratory fMRI study.

OBJECTIVE: Caffeine and glucose can have beneficial effects on cognitive performance. However, neural basis of these effects remain unknown. Our objective was to evaluate the effects of caffeine and glucose on sustained attention, using functional magnetic resonance imaging (fMRI). METHODS: Forty young right-handed, healthy, low caffeine-consuming subjects participated in the study. In a double-blind, randomised design, subjects received one of the following beverages: vehicle (water, 150 ml); vehicle plus 75 g of glucose; vehicle plus 75 mg of caffeine; vehicle plus 75 g of glucose and 75 mg of caffeine. Participants underwent two scanning fMRI sessions (before and 30 min after of the administration of the beverage). A continuous performance test was used to assess sustained attention. RESULTS: Participants who received combined caffeine and glucose had similar performance to the others but had a decrease in activation in the bilateral parietal and left prefrontal cortex. CONCLUSIONS: Since these areas have been related to the sustained attention and working memory processes, results would suggest that combined caffeine and glucose could increase the efficiency of the attentional system. However, more studies using larger samples and different levels of caffeine and glucose are necessary to better understand the combined effects of both substances.

Structural brain network of gifted children has a more integrated and versatile topology.

Gifted children learn more rapidly and effectively than others, presumably due to neurophysiological differences that affect efficiency in neuronal communication. Identifying the topological features that support its capabilities is relevant to understanding how the brain structure is related to intelligence. We proposed the analysis of the structural covariance network to assess which organizational patterns are characteristic of gifted children. The graph theory was used to analyse topological properties of structural covariance across a group of gifted children. The analysis was focused on measures of brain network integration, such as, participation coefficient and versatility, which quantifies the strength of specific modular affiliation of each regional node. We found that the gifted group network was more integrated (and less segregated) than the control group network. Brain regional nodes in the gifted group network had higher versatility and participation coefficient, indicating greater inter-modular communication mediated by connector hubs with links to many modules. Connector hubs of the networks of both groups were located mainly in association with neocortical areas (which had thicker cortex), with fewer hubs in primary or secondary neocortical areas (which had thinner cortex), as well as a few connector hubs in limbic cortex and insula. In the group of gifted children, a larger proportion of connector hubs were located in association cortex. In conclusion, gifted children have a more integrated and versatile brain network topology. This is compatible with the global workspace theory and other data linking integrative network topology to cognitive performance.

Hippocampal head atrophy after traumatic brain injury.

Traumatic brain injury (TBI) causes hippocampal damage. The hippocampus can be macroscopically divided into the head, body and tail, which differ in terms of their sensitivity to excitability and also in terms of their cortical connections. We investigated whether damage also varies according to the hippocampal area involved, and studied the relationship of hippocampal reductions with memory performance. Twenty TBI patients and matched controls were examined. MRI measurements were performed separately for the hippocampal head, body and tail. Memory outcome was measured by Rey's auditory verbal learning test, Rey's complex figure test and a modified version of Warrington's facial recognition memory test. Group comparison showed that patients had bilateral hippocampal atrophy, mainly involving the hippocampal head. Moreover, TBI subjects showed verbal memory deficits which presented slight correlations with left hippocampal head atrophy.

Spatiotemporal dynamics of the auditory novelty-P3 event-related brain potential.

The spatiotemporal dynamics of the cerebral network involved in novelty processing was studied by means of scalp current density (SCD) analysis of the novelty P3 (nP3) event-related brain potential (ERP). ERPs were recorded from 30 scalp electrodes at the occurrence of novel unpredictable environmental sounds during the performance of a visual discrimination task. Increased SCD was observed at left frontotemporal (FT3), bilateral temporoparietal (TP3 and TP4) and prefrontal locations (F8-F4 and F7-F3), suggesting novelty-P3 generators located in the left auditory cortex, and bilaterally in temporoparietal and prefrontal association regions. Additional increased SCD was found at a central location (Cz) and at superior parietal locations (P3-Pz-P4). The SCD of the nP3 was therefore generated at three successive, partially overlapping, stages of neuroelectric activation. At the central location, SCD started to be significant before the onset of the nP3 waveform, contributing solely to its early phase. At temporoparietal and left frontotemporal locations, nP3 electrophysiological activity was characterized by sustained current density, starting at about 210 ms and continuing during the full latency range of the response, including its early and late phases. At its late phase, the nP3 was characterized by sharp phasic current density at prefrontal and superior parietal locations, starting at about 290 ms and vanishing at around 385 ms. Taken together, these results provide the first evidence of the cerebral spatio-temporal dynamics underlying novelty processing.

Dopamine DRD2 Taq I polymorphism associates with caudate nucleus volume and cognitive performance in memory impaired subjects.

We studied the relationship among dopamine receptor D2 (DRD2) Taq I genetic polymorphism, caudate nucleus volumetry as measured using MRI and neuropsychological functions in 49 memory impaired older people. Compared with DRD2 A1 carriers, subjects homozygous for the DRD2 A2 allele performed poorer in a measure of general cognitive functioning (MMSE) and in long term verbal memory, and presented reduced left caudate nucleus volumes. Caudate nucleus atrophy correlated with cognitive measures influenced by the genetic polymorphism and with visual memory performance. Our findings suggest that among the aged with cognitive impairments, the homozygous status for the A2 allele of the DRD2 Taq I polymorphism is associated with diminished cognitive performance and increased atrophy in the striatum.

Residual hippocampal atrophy in asphyxiated term neonates.

BACKGROUND AND PURPOSE: Previous studies have shown the hippocampus and basal ganglia to be highly sensitive to hypoxic-ischemic insult. The authors' aim was to evaluate the long-term effects of perinatal asphyxia (PA) on the hippocampus and caudate nucleus in a group of participants born at term and who met the criteria for hypoxic-ischemic encephalopathy (HIE). Additionally, the authors looked for damage in other brain regions using voxel-based morphometry (VBM). METHODS: The sample consisted of 13 participants (8 boys and 5 girls) with a mean age at study of 16.23 years (+/- 2.89) with antecedents of perinatal asphyxia, diagnosed as moderate hypoxic-ischemic encephalopathy. A group of 13 healthy adolescents matched for age, sex, educational level, and social background were recruited as a comparison group. MR scans were acquired on a 1.5T Signa (General Electric, Milwaukee, WI) to evaluate hippocampal and caudate volumes and to perform VBM analysis. Finally, Rey's Auditory Verbal Learning Test was administered to evaluate verbal long-term memory. RESULTS: HIE participants were found to have bilateral hippocampal atrophy (P = .015) and gray matter damage in temporal and frontal lobes. The caudate nucleus showed no atrophic changes in PA participants, and VBM analysis did not reveal other consistent brain abnormalities. Verbal long-term memory was slightly worse in HIE participants. CONCLUSIONS: These findings indicate that PA produces hippocampal and other nonspecific long-term damage, which cannot be compensated for by plasticity mechanisms. However, this damage does not preclude normal development and scholarship.

[Neural bases of numerical processing and calculation]. / Bases neurales del procesamiento numérico y del cálculo.

AIM: To review the findings about neural correlates of number processing and arithmetic calculation, as well as the neuro-structural and neurofunctional imaging findings in patients with difficulties in this kind of abilities. DEVELOPMENT: The parietal lobe and specifically, the horizontal segment of the intraparietal sulcus, has become specialized in the internal representation of quantities, the abstract processing of magnitudes and the relation between them. On the other hand, the angular gyrus takes part in the verbal processing of certain tasks called arithmetical facts (for instance, multiplication tables and additions of small quantities). Prefrontal cortex, posterior part of temporal lobe, cingulate cortex and several subcortical regions are also involved in number processing. Empirical data have provided theoretical and anatomical models for number processing and calculation of which the Triple Code Model is currently the most accepted one. Moreover, implementation of neuroimaging techniques has demonstrated that patients who reported difficulties in numerical tasks show structural and functional involvement of the intraparietal sulcus. CONCLUSIONS: Neuroimaging techniques have allowed to specifying the neural basis of number processing and calculation. These findings can increase our knowledge of developmental dyscalculia and it's neuroanatomical and neurofunctional correlates. In the future, imaging and neuropsychological data could lead us to more accurate diagnosis methods and better educational programs, in order to improve numerical abilities of patients affected by dyscalculia.

Functional connectivity of the hippocampus in elderly with mild memory dysfunction carrying the APOE epsilon4 allele.

The purpose of the present study was to evaluate functional connectivity of the hippocampus during a fMRI face-name learning task in a group of elders with mild memory impairment on the basis of the presence or absence of the APOE epsilon4 allele. Twelve epsilon4 carriers and 20 non-carriers with mild memory dysfunction and exhibiting equivalent performance in clinical evaluations of global cognitive function and memory were studied. Subjects underwent a fMRI session consisting of a face-name encoding memory task. Following scanning, subjects were asked to pair faces with their corresponding proper name. Functional connectivity of the hippocampus was measured by using coherence analysis to evaluate the activity of brain circuits related to memory encoding processes. In contrast to non-APOE epsilon4 allele bearers, APOE epsilon4 carriers showed enhanced connectivity with the anterior cingulate, inferior parietal/postcentral gyrus region and the caudate nucleus. Enhanced hippocampal connectivity with additional brain regions in APOE epsilon4 allele carriers during the performance of an associative memory task may reveal the existence of additional activity in the cortico-subcortical network engaged during memory encoding in subjects carrying this genetic variant.

Corpus callosum atrophy in adolescents with antecedents of moderate perinatal asphyxia.

BACKGROUND: The corpus callosum (CC) is a cerebral structure that reflects cognitive status in several neurological pathologies. Visual inspection of MRI has shown that hypoxic-ischemic encephalopathy(HIE) causes callosal damage. PRIMARY OBJECTIVE: To quantify the CC surface in a sample of patients with antecedents of HIE and a group of matched controls. RESEARCH DESIGN: Comparisons of CC measures among control subjects, mild HIE patients and moderateHIE patients as well as correlates of CC surface and neuropsychological performance. METHODS: Twenty-one adolescent patients with childhood antecedents of HIE were compared to 21 controls. ANALYZE software was used to semi-automatically measure the CC area. MAIN OUTCOMES AND RESULTS: Patients with moderate HIE showed corpus callosum reduction. The isthmus and genus were the most affected regions. Corpus callosum size correlated with cognitive function. CONCLUSIONS: Corpus callosum quantification provides new evidence of subtle residual deficits in subjects with HIE antecedents without apparent neurological sequelae.

Bases cerebrales de la atención sostenida y la memoria de trabajo: un estudio de resonancia magnética funcional basado en el Continuous Performance Test / Cerebral networks of sustained attention and working memory: a functional magnetic resonance imaging study based on the Continuous Performance Test

Introducción. Uno de los paradigmas más utilizados en el estudio de la atención es el Continuous Performance Test (CPT). La versión de pares idénticos (CPT-IP) se ha utilizado ampliamente para evaluar los déficits de atención en los trastornos del neurodesarrollo, neurológicos y psiquiátricos. Sin embargo, la localización de la activación cerebral de las redes atencionales varía significativamente según el diseño de resonancia magnética funcional (RMf) usado. Objetivo. Diseñar una tarea para evaluar la atención sostenida y la memoria de trabajo mediante RMf para proporcionar datos de investigación relacionados con la localización y el papel de estas funciones. Sujetos y métodos. El estudio contó con la participación de 40 estudiantes, todos ellos diestros (50%, mujeres; rango: 18-25 años). La tarea de CPT-IP se diseñó como una tarea de bloques, en la que se combinaban los períodos CPT-IP con los de reposo. Resultados. La tarea de CPT-IP utilizada activa una red formada por regiones frontales, parietales y occipitales, y éstas se relacionan con funciones ejecutivas y atencionales. Conclusiones. La tarea de CPT-IP utilizada en nuestro trabajo proporciona datos normativos en adultos sanos para el estudio del sustrato neural de la atención sostenida y la memoria de trabajo. Estos datos podrían ser útiles para evaluar trastornos que cursan con déficits en memoria de trabajo y en atención sostenida (AU)

Introduction. One of the most used paradigms in the study of attention is the Continuous Performance Test (CPT). The identical pairs version (CPT-IP) has been widely used to evaluate attention deficits in developmental, neurological and psychiatric disorders. However, the specific locations and the relative distribution of brain activation in networks identified with functional imaging, varies significantly with differences in task design. AIM. To design a task to evaluate sustained attention using functional magnetic resonance imaging (fMRI), and thus to provide data for research concerned with the role of these functions. SUBJECTS AND METHODS. Forty right-handed, healthy students (50% women; age range: 18-25 years) were recruited. A CPT-IP implemented as a block design was used to assess sustained attention during the fMRI session. RESULTS. The behavioural results from the CPT-IP task showed a good performance in all subjects, higher than 80% of hits. fMRI results showed that the used CPT-IP task activates a network of frontal, parietal and occipital areas, and that these are related to executive and attentional functions. CONCLUSIONS. In relation to the use of the CPT to study of attention and working memory, this task provides normative data in healthy adults, and it could be useful to evaluate disorders which have attentional and working memory déficits (AU)

Bases neurales del procesamiento numérico y del cálculo / Neural bases of numerical processing and calculation

Objetivo. Revisar los hallazgos existentes sobre el sustrato neural del procesamiento numérico y del cálculo, así como las alteraciones neuroestructurales y neurofuncionales detectadas en los pacientes con trastornos en dichas habilidades. Desarrollo. La participación del lóbulo parietal resulta crucial. En concreto, el segmento horizontal del surco intraparietal se halla especializado en la representación interna de las cantidades, el procesamiento abstracto de las magnitudes y su relación. Por su parte, el giro angular participa en el procesamiento verbal de determinadas tareas aritméticas y permite la resolución de los ‘hechos matemáticos’ (tablas de multiplicación y adición de pequeñas cantidades). La corteza prefrontal, la parte posterior del lóbulo temporal, la corteza cingulada y distintas regiones subcorticales están también implicadas. Estos resultados han permitido elaborar modelos teóricos explicativos del procesamiento numérico y del cálculo, siendo el modelo del ‘triple código’ el que tiene más soporte. Por su parte, el estudio mediante técnicas de neuroimagen ha puesto de manifiesto que los pacientes con dificultades en el procesamiento numérico presentan alteraciones estructurales y funcionales en el surco intraparietal. Conclusiones. Las técnicas de neuroimagen han permitido delimitar las bases neurales del procesamiento numérico y del cálculo. Estos hallazgos son la base sobre la que estudiar las alteraciones cerebrales asociadas a la discalculia, de manera que, en el futuro, la complementación con los datos neuropsicológicos podría ayudar a mejorar su diagnóstico y a diseñar programas individualizados de reeducación orientados a la mejora en las habilidades numéricas de estos pacientes (AU)

Aim. To review the findings about neural correlates of number processing and arithmetic calculation, as well as the neurostructural and neurofunctional imaging findings in patients with difficulties in this kind of abilities. Development. The parietal lobe and specifically, the horizontal segment of the intraparietal sulcus, has become specialized in the internal representation of quantities, the abstract processing of magnitudes and the relation between them. On the other hand, the angular gyrus takes part in the verbal processing of certain tasks called arithmetical facts (for instance, multiplication tables and additions of small quantities). Prefrontal cortex, posterior part of temporal lobe, cingulate cortex and several subcortical regions are also involved in number processing. Empirical data have provided theoretical and anatomical models for number processing and calculation of which the Triple Code Model is currently the most accepted one. Moreover, implementation of neuroimaging techniques has demonstrated that patients who reported difficulties in numerical tasks show structural and functional involvement of the intraparietal sulcus. Conclusions. Neuroimaging techniques have allowed to specifying the neural basis of number processing and calculation. These findings can increase our knowledge of developmental dyscalculia and it’s neuroanatomical and neurofunctional correlates. In the future, imaging and neuropsychological data could lead us to more accurate diagnosis methods and better educational programs, in order to improve numerical abilities of patients affected by dyscalculia (AU)