Parietal hyper-connectivity, aberrant brain organization, and circuit-based biomarkers in children with mathematical disabilities.
Brain Structural Integrity and Intrinsic Functional Connectivity Forecast 6 Year Longitudinal Growth in Children's Numerical Abilities
JOURNAL OF NEUROSCIENCE
2015; 35 (33): 11743-11750
Mathematical disabilities (MD) have a negative life-long impact on professional success, employment, and health outcomes. Yet little is known about the intrinsic functional brain organization that contributes to poor math skills in affected children. It is now increasingly recognized that math cognition requires coordinated interaction within a large-scale fronto-parietal network anchored in the intraparietal sulcus (IPS). Here we characterize intrinsic functional connectivity within this IPS-network in children with MD, relative to a group of typically developing (TD) children who were matched on age, gender, IQ, working memory, and reading abilities. Compared to TD children, children with MD showed hyper-connectivity of the IPS with a bilateral fronto-parietal network. Importantly, aberrant IPS connectivity patterns accurately discriminated children with MD and TD children, highlighting the possibility for using IPS connectivity as a brain-based biomarker of MD. To further investigate regional abnormalities contributing to network-level deficits in children with MD, we performed whole-brain analyses of intrinsic low-frequency fluctuations. Notably, children with MD showed higher low-frequency fluctuations in multiple fronto-parietal areas that overlapped with brain regions that exhibited hyper-connectivity with the IPS. Taken together, our findings suggest that MD in children is characterized by robust network-level aberrations, and is not an isolated dysfunction of the IPS. We hypothesize that intrinsic hyper-connectivity and enhanced low-frequency fluctuations may limit flexible resource allocation, and contribute to aberrant recruitment of task-related brain regions during numerical problem solving in children with MD.
View details for DOI 10.1111/desc.12399
View details for PubMedID 26874919
The functional anatomy of single-digit arithmetic in children with developmental dyslexia
2014; 101: 644-652
Early numerical proficiency lays the foundation for acquiring quantitative skills essential in today's technological society. Identification of cognitive and brain markers associated with long-term growth of children's basic numerical computation abilities is therefore of utmost importance. Previous attempts to relate brain structure and function to numerical competency have focused on behavioral measures from a single time point. Thus, little is known about the brain predictors of individual differences in growth trajectories of numerical abilities. Using a longitudinal design, with multimodal imaging and machine-learning algorithms, we investigated whether brain structure and intrinsic connectivity in early childhood are predictive of 6 year outcomes in numerical abilities spanning childhood and adolescence. Gray matter volume at age 8 in distributed brain regions, including the ventrotemporal occipital cortex (VTOC), the posterior parietal cortex, and the prefrontal cortex, predicted longitudinal gains in numerical, but not reading, abilities. Remarkably, intrinsic connectivity analysis revealed that the strength of functional coupling among these regions also predicted gains in numerical abilities, providing novel evidence for a network of brain regions that works in concert to promote numerical skill acquisition. VTOC connectivity with posterior parietal, anterior temporal, and dorsolateral prefrontal cortices emerged as the most extensive network predicting individual gains in numerical abilities. Crucially, behavioral measures of mathematics, IQ, working memory, and reading did not predict children's gains in numerical abilities. Our study identifies, for the first time, functional circuits in the human brain that scaffold the development of numerical skills, and highlights potential biomarkers for identifying children at risk for learning difficulties.Children show substantial individual differences in math abilities and ease of math learning. Early numerical abilities provide the foundation for future academic and professional success in an increasingly technological society. Understanding the early identification of poor math skills has therefore taken on great significance. This work provides important new insights into brain structure and connectivity measures that can predict longitudinal growth of children's math skills over a 6 year period, and may eventually aid in the early identification of children who might benefit from targeted interventions.
View details for DOI 10.1523/JNEUROSCI.0216-15.2015
View details for Web of Science ID 000362499700025
From student to steward: the Interdisciplinary Program in Neuroscience at Georgetown University as a case study in professional development during doctoral training.
Medical education online
2014; 19: 22623
Some arithmetic procedures, such as addition of small numbers, rely on fact retrieval mechanisms supported by left hemisphere perisylvian language areas, while others, such as subtraction, rely on procedural-based mechanisms subserved by bilateral parietal cortices. Previous work suggests that developmental dyslexia, a reading disability, is accompanied by subtle deficits in retrieval-based arithmetic, possibly because of compromised left hemisphere function. To test this prediction, we compared brain activity underlying arithmetic problem solving in children with and without dyslexia during addition and subtraction operations using a factorial design. The main effect of arithmetic operation (addition versus subtraction) for both groups combined revealed activity during addition in the left superior temporal gyrus and activity during subtraction in the bilateral intraparietal sulcus, the right supramarginal gyrus and the anterior cingulate, consistent with prior studies. For the main effect of diagnostic group (dyslexics versus controls), we found less activity in dyslexic children in the left supramarginal gyrus. Finally, the interaction analysis revealed that while the control group showed a strong response in the right supramarginal gyrus for subtraction but not for addition, the dyslexic group engaged this region for both operations. This provides physiological evidence in support of the theory that children with dyslexia, because of disruption to left hemisphere language areas, use a less optimal route for retrieval-based arithmetic, engaging right hemisphere parietal regions typically used by good readers for procedural-based arithmetic. Our results highlight the importance of language processing for mathematical processing and illustrate that children with dyslexia have impairments that extend beyond reading.
View details for DOI 10.1016/j.neuroimage.2014.07.028
View details for Web of Science ID 000344931800058
View details for PubMedID 25067820
Sex-specific gray matter volume differences in females with developmental dyslexia.
Brain structure & function
A key facet of professional development is the formation of professional identity. At its most basic level, professional identity for a scientist centers on mastery of a discipline and the development of research skills during doctoral training. To develop a broader understanding of professional identity in the context of doctoral training, the Carnegie Initiative on the Doctorate (CID) ran a multi-institutional study from 2001 to 2005. A key outcome of the CID was the development of the concept of 'stewards of the discipline'. The Interdisciplinary Program in Neuroscience (IPN) at Georgetown University participated in CID from 2003 to 2005. Here, we describe the IPN and highlight the programmatic developments resulting from participation in the CID. In particular, we emphasize programmatic activities that are designed to promote professional skills in parallel with scientific development. We describe activities in the domains of leadership, communication, teaching, public outreach, ethics, collaboration, and mentorship. Finally, we provide data that demonstrate that traditional metrics of academic success are not adversely affected by the inclusion of professional development activities in the curricula. By incorporating these seven 'professional development' activities into the required coursework and dissertation research experience, the IPN motivates students to become stewards of the discipline.
View details for PubMedID 25005356
Developmental dyslexia, characterized by unexpected reading difficulty, is associated with anomalous brain anatomy and function. Previous structural neuroimaging studies have converged in reports of less gray matter volume (GMV) in dyslexics within left hemisphere regions known to subserve language. Due to the higher prevalence of dyslexia in males, these studies are heavily weighted towards males, raising the question whether studies of dyslexia in females only and using the same techniques, would generate the same findings. In a replication study of men, we obtained the same findings of less GMV in dyslexics in left middle/inferior temporal gyri and right postcentral/supramarginal gyri as reported in the literature. However, comparisons in women with and without dyslexia did not yield left hemisphere differences, and instead, we found less GMV in right precuneus and paracentral lobule/medial frontal gyrus. In boys, we found less GMV in left inferior parietal cortex (supramarginal/angular gyri), again consistent with previous work, while in girls differences were within right central sulcus, spanning adjacent gyri, and left primary visual cortex. Our investigation into anatomical variants in dyslexia replicates existing studies in males, but at the same time shows that dyslexia in females is not characterized by involvement of left hemisphere language regions but rather early sensory and motor cortices (i.e., motor and premotor cortex, primary visual cortex). Our findings suggest that models on the brain basis of dyslexia, primarily developed through the study of males, may not be appropriate for females and suggest a need for more sex-specific investigations into dyslexia.
View details for DOI 10.1007/s00429-013-0552-4
View details for PubMedID 23625146