Left hemisphere lateralization of the limbic system and frontoparietal network (FPN) correlates with positive and negative symptom improvement following cannabidiol (CBD) administration in psychosis and ultra-high risk (UHR) populations: A voxel-wise meta-analysis.

This voxel-wise meta-analysis assesses current findings about the neural correlates of cannabidiol on the positive and negative symptoms among individuals with psychosis or ultra-high risk (UHR) for psychosis. We used PubMed, EMBASE, and ScienceDirect as primary databases and initially retrieved 157 studies. After applying our eligibility criteria, 13 studies remained for inclusion. Ten studies focused on psychosis. Three studies focused on UHR. Quality assessment was performed for included articles using the RoB2 instrument. Statistical analysis implicated a voxel-wise meta-analysis of different task paradigms (emotion recognition, verbal memory recall, and inhibitory control) with a jackknife sensitivity measure, Egger's test of random effects, and a meta-regression with relevant covariates. Article quality was determined to be primarily low risk of bias, with some elements of unclear bias figuring across studies. Our results showed robust, convergent correlations between CBD administration and left hemisphere lateralization of limbic system and frontoparietal network (FPN) subregions across task paradigms in psychosis and UHR populations. Our meta-regression revealed that decreased limbic system activity correlated with positive symptom improvements, and decreased FPN activity correlated with negative symptom improvements. Lastly, sensitivity analyses determined that there was minimal risk bias or risk of confounding variables unduly influencing our meta-analyses (p > 0.05).

Therapeutic interventions impact brain function and promote post-traumatic growth in adults living with post-traumatic stress disorder: A systematic review and meta-analysis of functional magnetic resonance imaging studies.

Introduction: The present systematic review and meta-analysis explores the impacts of cognitive processing therapy (CPT), eye movement desensitization and reprocessing (EMDR), and prolonged exposure (PE) therapy on neural activity underlying the phenomenon of post-traumatic growth for adult trauma survivors. Methods: We utilized the following databases to conduct our systematic search: Boston College Libraries, PubMed, MEDLINE, and PsycINFO. Our initial search yielded 834 studies for initial screening. We implemented seven eligibility criteria to vet articles for full-text review. Twenty-nine studies remained for full-text review after our systematic review process was completed. Studies were subjected to several levels of analysis. First, pre-and post- test post-traumatic growth inventory (PTGI) scores were collected from all studies and analyzed through a forest plot using Hedges' g. Next, Montreal Neurological Institute (MNI) coordinates and t-scores were collected and analyzed using an Activation Likelihood Estimation (ALE) to measure brain function. T-scores and Hedges' g values were then analyzed using Pearson correlations to determine if there were any relationships between brain function and post-traumatic growth for each modality. Lastly, all studies were subjected to a bubble plot and Egger's test to assess risk of publication bias across the review sample. Results: Forest plot results indicated that all three interventions had a robust effect on PTGI scores. ALE meta-analysis results indicated that EMDR exhibited the largest effect on brain function, with the R thalamus (t = 4.23, p < 0.001) showing robust activation, followed closely by the R precuneus (t = 4.19, p < 0.001). Pearson correlation results showed that EMDR demonstrated the strongest correlation between increased brain function and PTGI scores (r = 0.910, p < 0.001). Qualitative review of the bubble plot indicated no obvious traces of publication bias, which was corroborated by the results of the Egger's test (p = 0.127). Discussion: Our systematic review and meta-analysis showed that CPT, EMDR, and PE each exhibited a robust effect on PTG impacts across the course of treatment. However, when looking closer at comparative analyses of neural activity (ALE) and PTGI scores (Pearson correlation), EMDR exhibited a more robust effect on PTG impacts and brain function than CPT and PE.

Stress and Susceptibility: A Systematic Review of Prenatal Epigenetic Risks for Developing Post-Traumatic Stress Disorder.

This review aims to systematically assess the current literature about prenatal epigenetic markers that lead to post-traumatic stress disorder susceptibility across the lifespan. Studies included in this review met several research criteria: Studies included (1) participants with a PTSD diagnosis according to the DSM-5, (2) prenatal epigenetic marker data that could be analyzed, and (3) explicit references to postnatal PTSD susceptibility. Our study sample fit within a timeframe of 2002 (the earliest recorded studies of prenatal susceptibility to post-traumatic stress disorder in the databases used) and February 2021 when the literature search for this review was terminated. Studies for this review were collated from PubMed, MEDLINE, Science Direct, and Boston College School of Social Work Library databases. A systematic search was conducted in these databases using basic keyword terms, such as "PSTD resilience" and "PTSD vulnerability," and then adding clarifying terms to refine specific searches, such as "epigenetics," "genetics," "epigenetic markers," "haplotypes," and "mRNA methylation." Based on these criteria and research methods, 33 studies remained for inclusion in the review sample. This review suggests that BDNF Val66-Met, a polymorphism of FKBP5, and an altered messenger ribonucleic acid methylation marker in NR3C1 present most often in cases of PTSD. These epigenetic markers might be implicated in central neurological processes related to post-traumatic stress disorder symptomatology.

The Neurophysiology Behind Trauma-Focused Therapy Modalities Used to Treat Post-Traumatic Stress Disorder Across the Life Course: A Systematic Review.

This review presents the current state of understanding of trauma-informed modalities in light of current research in neuroscience, analyzing which brain structures and processes are impacted by these modalities. Studies included in the present review met the inclusion criteria of 1) addressing post-traumatic stress disorder (PTSD) in a specific population, 2) treatment of PTSD using any of the evidence-based trauma-informed modalities considered in this review, and 3) presenting functional magnetic resonance imagery (fMRI) data, derived from BOLD signals and voxel-compression maps, of brain structures impacted by these trauma-informed modalities. Articles for this review were collated through PubMed and MEDLINE, using key terms in descending order, such as 'childhood trauma', 'adolescent trauma', and 'adulthood trauma', to 'PTSD', 'fMRI', and so on, depending on the modality in question. Based on these criteria and research methods, 37 studies remained for inclusion in the present review. Among a number of critical findings, this review demonstrates that eye movement desensitization and reprocessing (EMDR) and mindfulness therapy effectively deactivate hindbrain regions implicated in the downregulation of autonomic nervous system (ANS) hyperarousal. This review also shows that trauma-focused cognitive behavioral therapy (TF-CBT) and EMDR activate the hippocampus, anterior cingulate cortex (ACC), medial prefrontal cortex (mPFC), and orbitofrontal cortex (OFC)-areas that are implicated in crucial cognitive, affective, and behavioral processes that aid trauma survivors in navigating their challenges.

Fear of sleep and sleep quality mediate the relationship between trauma exposure and suicide attempt in adolescents.

Prior work has established bivariate associations between suicidal thoughts and behaviors, trauma exposure and sleep disturbance broadly. Specifically, this study tested whether fear of sleep and sleep quality mediated the association between trauma exposure and suicide attempt. Participants (N = 100) were adolescents admitted to an inpatient psychiatric program for suicidality. Trauma exposure history was retrieved from admission notes and participants completed self-report surveys assessing sleep quality, fear of sleep and number of suicide attempts within the previous month. Structural equation modelling was used to investigate the relationships between childhood trauma, fear of sleep, sleep quality, and suicide attempt. Path analysis was used to investigate the indirect effects from trauma exposure to suicide attempt through fear of sleep, and sleep quality. Path analysis revealed a significant indirect effect from trauma exposure to suicide attempt through fear of sleep and sleep quality. Our findings suggest that a significant portion of the association between trauma exposure and suicide attempts in adolescence may be explained by the negative impact of trauma exposure on sleep. Fear of sleep may increase the risk of a suicide attempt by negatively impacting sleep quality. Future studies should investigate whether interventions targeting sleep and fear of sleep reduce the association between trauma and suicide attempt.

Brain basis of cognitive resilience: Prefrontal cortex predicts better reading comprehension in relation to decoding.

OBJECTIVE: The ultimate goal of reading is to understand written text. To accomplish this, children must first master decoding, the ability to translate printed words into sounds. Although decoding and reading comprehension are highly interdependent, some children struggle to decode but comprehend well, whereas others with good decoding skills fail to comprehend. The neural basis underlying individual differences in this discrepancy between decoding and comprehension abilities is virtually unknown. METHODS: We investigated the neural basis underlying reading discrepancy, defined as the difference between reading comprehension and decoding skills, in a three-part study: 1) The neuroanatomical basis of reading discrepancy in a cross-sectional sample of school-age children with a wide range of reading abilities (Experiment-1; n = 55); 2) Whether a discrepancy-related neural signature is present in beginning readers and predictive of future discrepancy (Experiment-2; n = 43); and 3) Whether discrepancy-related regions are part of a domain-general or a language specialized network, utilizing the 1000 Functional Connectome data and large-scale reverse inference from Neurosynth.org (Experiment-3). RESULTS: Results converged onto the left dorsolateral prefrontal cortex (DLPFC), as related to having discrepantly higher reading comprehension relative to decoding ability. Increased gray matter volume (GMV) was associated with greater discrepancy (Experiment-1). Region-of-interest (ROI) analyses based on the left DLPFC cluster identified in Experiment-1 revealed that regional GMV within this ROI in beginning readers predicted discrepancy three years later (Experiment-2). This region was associated with the fronto-parietal network that is considered fundamental for working memory and cognitive control (Experiment-3). INTERPRETATION: Processes related to the prefrontal cortex might be linked to reading discrepancy. The findings may be important for understanding cognitive resilience, which we operationalize as those individuals with greater higher-order reading skills such as reading comprehension compared to lower-order reading skills such as decoding skills. Our study provides insights into reading development, existing theories of reading, and cognitive processes that are potentially significant to a wide range of reading disorders.

Recognizing Psychiatric Comorbidity With Reading Disorders.

Reading disorder (RD), a specific learning disorder (SLD) of reading that includes impairment in word reading, reading fluency, and/or reading comprehension, is common in the general population but often is not comprehensively understood or assessed in mental health settings. In education settings, comorbid mental and associated disorders may be inadequately integrated into intervention plans. Assessment and intervention for RD may be delayed or absent in children with frequently co-occurring mental disorders not fully responding to treatment in both school and mental health settings. To address this oversight, this review summarizes current knowledge regarding RDs and common comorbid or co-occurring disorders that are important for mental health and school settings. We chose to highlight RD because it is the most common SLD, and connections to other often comorbid disorders have been more thoroughly described in the literature. Much of the literature we describe is on decoding-based RD (or developmental dyslexia) as it is the most common form of RD. In addition to risk for academic struggle and social, emotional, and behavioral problems, those with RD often show early evidence of combined or intertwined Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition childhood disorders. These include attention deficit hyperactivity disorder, anxiety and depression, disruptive, impulse-control, and conduct disorders, autism spectrum disorders, and other SLDs. The present review highlights issues and areas of controversy within these comorbidities, as well as directions for future research. An interdisciplinary, integrated approach between mental health professionals and educators can lead to comprehensive and targeted treatments encompassing both academic and mental health interventions. Such targeted treatments may contribute to improved educational and health-related outcomes in vulnerable youth. While there is a growing research literature on this association, more studies are needed of when to intervene and of the early and long-term benefits of comprehensive intervention.

Neurobiological Bases of Reading Disorder Part II: The Importance of Developmental Considerations in Typical and Atypical Reading.

Decoding-based reading disorder (RD; aka developmental dyslexia) is one of the most common neurodevelopmental disorders, affecting approximately 5-10% of school-aged children across languages. Even though neuroimaging studies suggest an impairment of the left reading network in RD, the onset of this deficit and its developmental course, which may include constancy and change, is largely unknown. There is now growing evidence that the recruitment of brain networks underlying perceptual, cognitive and linguistic processes relevant to reading acquisition varies with age. These age-dependent changes may in turn impact the neurocognitive characteristics of RD observed at specific developmental stages. Here we synthesize findings from functional and structural magnetic resonance imaging (MRI) studies to increase our understanding of the developmental time course of the neural bases underlying (a)typical reading. We first provide an overview of the brain bases of typical and atypical (impaired) reading. Next we describe how the understanding of RD can be deepened through scientific attention to age effects, for example, by integrating findings from cross-sectional studies of RD at various ages. Finally, we accent findings from extant longitudinal studies that directly examine developmental reading trajectories beginning in the preliterate stage at both group and individual levels. Although science is at the very early stage of understanding developmental aspects of neural deficits in RD, evidence to date characterizes RD by atypical brain maturation. We know that reading impairment may adversely impact multiple life domains such as academic achievement and social relationships, and unfortunately, that these negative outcomes can persist and compound into adulthood. We contend that exploring the developmental trajectories of RD will contribute to a greater understanding of how neural systems support reading acquisition. Further, we propose and cite evidence that the etiology of RD can be better investigated by distinguishing primary deficits from secondary impairments unfolding along development. These exciting and modern investigatory efforts can also indirectly contribute to a centered practice of early and accurate identification and optimal intervention to support the development of foundational pre-literacy skills and fluent reading. In sum, integrating a developmental understanding into the science and practice of reading acquisition and intervention is both possible and necessary.

The matter of motivation: Striatal resting-state connectivity is dissociable between grit and growth mindset.

The current study utilized resting-state functional magnetic resonance imaging (fMRI) to examine how two important non-cognitive skills, grit and growth mindset, are associated with cortico-striatal networks important for learning. Whole-brain seed-to-voxel connectivity was examined for dorsal and ventral striatal seeds. While both grit and growth mindset were associated with functional connectivity between ventral striatal and bilateral prefrontal networks thought to be important for cognitive-behavioral control. There were also clear dissociations between the neural correlates of the two constructs. Grit, the long-term perseverance towards a goal or set of goals, was associated with ventral striatal networks including connectivity to regions such as the medial prefrontal and rostral anterior cingulate cortices implicated in perseverance, delay and receipt of reward. Growth mindset, the belief that effort can improve talents, notably intelligence, was associated with both ventral and dorsal striatal connectivity with regions thought to be important for error-monitoring, such as dorsal anterior cingulate cortex. Our findings may help construct neurocognitive models of these non-cognitive skills and have critical implications for character education. Such education is a key component of social and emotional learning, ensuring that children can rise to challenges in the classroom and in life.

Female-Specific Intergenerational Transmission Patterns of the Human Corticolimbic Circuitry.

Parents have large genetic and environmental influences on offspring's cognition, behavior, and brain. These intergenerational effects are observed in mood disorders, with particularly robust association in depression between mothers and daughters. No studies have thus far examined the neural bases of these intergenerational effects in humans. Corticolimbic circuitry is known to be highly relevant in a wide range of processes, including mood regulation and depression. These findings suggest that corticolimbic circuitry may also show matrilineal transmission patterns. Therefore, we examined human parent-offspring association in this neurocircuitry and investigated the degree of association in gray matter volume between parent and offspring. We used voxelwise correlation analysis in a total of 35 healthy families, consisting of parents and their biological offspring. We found positive associations of regional gray matter volume in the corticolimbic circuit, including the amygdala, hippocampus, anterior cingulate cortex, and ventromedial prefrontal cortex between biological mothers and daughters. This association was significantly greater than mother-son, father-daughter, and father-son associations. The current study suggests that the corticolimbic circuitry, which has been implicated in mood regulation, shows a matrilineal-specific transmission patterns. Our preliminary findings are consistent with what has been found behaviorally in depression and may have clinical implications for disorders known to have dysfunction in mood regulation such as depression. Studies such as ours will likely bridge animal work examining gene expression in the brains and clinical symptom-based observations and provide promising ways to investigate intergenerational transmission patterns in the human brain. SIGNIFICANCE STATEMENT: Parents have large genetic and environmental influences on the offspring, known as intergenerational effects. Specifically, depression has been shown to exhibit strong matrilineal transmission patterns. Although intergenerational transmission patterns in the human brain are virtually unknown, this would suggest that the corticolimbic circuitry relevant to a wide range of processes including mood regulation may also show matrilineal transmission patterns. Therefore, we examined the degree of association in corticolimbic gray matter volume (GMV) between parent and offspring in 35 healthy families. We found that positive correlations in maternal corticolimbic GMV with daughters were significantly greater than other parent-offspring dyads. Our findings provide new insight into the potential neuroanatomical basis of circuit-based female-specific intergenerational transmission patterns in depression.

Utilizing biopsychosocial and strengths-based approaches within the field of child health: what we know and where we can grow.

We continue to increase our understanding of the experiences and settings that contribute to positive developmental outcomes in childhood, and those that confer greater risk. Although the mechanisms by which the risk and protective factors affect developmental outcomes need to be further elucidated through research, converging findings from the field of child health (spanning both physical and mental health) indicate that a biopsychosocial approach is useful. Here, we examine the evidence that early experiences confer both risk and protective processes on biopsychosocial development in childhood, and touch on some implications for the life course. Although this interdisciplinary field of research has already garnered substantial attention, here we aim to highlight the opportunity to use a strengths-based approach with the biopsychosocial model, with particular focus on children who experience prolonged stress. We close with consideration for future directions with an emphasis on policy and practice in clinical and educational settings to improve well-being in these early stages of the life course.

The utility of neuroimaging studies for informing educational practice and policy in reading disorders.

Educational neuroscience is an emerging scientific field that brings together researchers from neuroscience, psychology, and education to explore the neurocognitive processes underlying educational practice and theory. In this brief article, we take reading disorder (RD, also known as developmental dyslexia) as an example, and explore trends in neuroimaging research, which may have future implications for educational practice and policy. Specifically, we present two examples that have been central to research efforts in our laboratory: (a) utilizing multimodal neuroimaging to optimize criteria to diagnose RD, and (b) identifying neuroimaging markers that predict future academic outcomes. Such research is faced with important challenges, and rigorous validation is necessary before any claims of the widespread practical utility of neuroimaging can be made. Nevertheless, we contend that neuroimaging studies offer opportunities for providing critical information that could lead to advancing theory of reading and RD. This could in turn lead to better diagnostic criteria and more accurate and earlier identification of RD.

White matter morphometric changes uniquely predict children's reading acquisition.

This study examined whether variations in brain development between kindergarten and Grade 3 predicted individual differences in reading ability at Grade 3. Structural MRI measurements indicated that increases in the volume of two left temporo-parietal white matter clusters are unique predictors of reading outcomes above and beyond family history, socioeconomic status, and cognitive and preliteracy measures at baseline. Using diffusion MRI, we identified the left arcuate fasciculus and superior corona radiata as key fibers within the two clusters. Bias-free regression analyses using regions of interest from prior literature revealed that volume changes in temporo-parietal white matter, together with preliteracy measures, predicted 56% of the variance in reading outcomes. Our findings demonstrate the important contribution of developmental differences in areas of left dorsal white matter, often implicated in phonological processing, as a sensitive early biomarker for later reading abilities, and by extension, reading difficulties.

Functional neuroanatomical evidence for the double-deficit hypothesis of developmental dyslexia.

The double-deficit hypothesis of dyslexia posits that both rapid naming and phonological impairments can cause reading difficulties, and that individuals who have both of these deficits show greater reading impairments compared to those with a single deficit. Despite extensive behavioral research, the brain basis of poor reading with a double-deficit has never been investigated. The goal of the study was to evaluate the double-deficit hypothesis using functional MRI. Activation patterns during a printed word rhyme judgment task in 90 children with a wide range of reading abilities showed dissociation between brain regions that were sensitive to phonological awareness (left inferior frontal and inferior parietal regions) and rapid naming (right cerebellar lobule VI). More specifically, the double-deficit group showed less activation in the fronto-parietal reading network compared to children with only a deficit in phonological awareness, who in turn showed less activation than the typically-reading group. On the other hand, the double-deficit group showed less cerebellar activation compared to children with only a rapid naming deficit, who in turn showed less activation than the typically-reading children. Functional connectivity analyses revealed that bilateral prefrontal regions were key for linking brain regions associated with phonological awareness and rapid naming, with the double-deficit group being the most aberrant in their connectivity. Our study provides the first functional neuroanatomical evidence for the double-deficit hypothesis of developmental dyslexia.

Neuroimaging correlates of handwriting quality as children learn to read and write.

Reading and writing are related but separable processes that are crucial skills to possess in modern society. The neurobiological basis of reading acquisition and development, which critically depends on phonological processing, and to a lesser degree, beginning writing as it relates to letter perception, are increasingly being understood. Yet direct relationships between writing and reading development, in particular, with phonological processing is not well understood. The main goal of the current preliminary study was to examine individual differences in neurofunctional and neuroanatomical patterns associated with handwriting in beginning writers/readers. In 46 5-6 year-old beginning readers/writers, ratings of handwriting quality, were rank-ordered from best to worst and correlated with brain activation patterns during a phonological task using functional MRI, and with regional gray matter volume from structural T1 MRI. Results showed that better handwriting was associated negatively with activation and positively with gray matter volume in an overlapping region of the pars triangularis of right inferior frontal gyrus. This region, in particular in the left hemisphere in adults and more bilaterally in young children, is known to be important for decoding, phonological processing, and subvocal rehearsal. We interpret the dissociation in the directionality of the association in functional activation and morphometric properties in the right inferior frontal gyrus in terms of neural efficiency, and suggest future studies that interrogate the relationship between the neural mechanisms underlying reading and writing development.

The neural basis of humour processing.

Humour is a vital component of human socio-affective and cognitive functioning. Recent advances in neuroscience have enabled researchers to explore this human attribute in children and adults. Humour seems to engage a core network of cortical and subcortical structures, including temporo-occipito-parietal areas involved in detecting and resolving incongruity (mismatch between expected and presented stimuli); and the mesocorticolimbic dopaminergic system and the amygdala, key structures for reward and salience processing. Examining personality effects and sex differences in the neural correlates of humour may aid in understanding typical human behaviour and the neural mechanisms underlying neuropsychiatric disorders, which can have dramatic effects on the capacity to experience social reward.

Humor processing in children: influence of temperament, age and IQ.

Emerging evidence from fMRI studies suggests that humor processing is a specific social cognitive-affective human function that comprises two stages. The first stage (cognitive humor component) involves the detection and resolution of incongruity, and is associated with activity in temporo-occipito-parietal brain areas. The second stage (emotional humor component) comprises positive feelings related to mirth/reward, and is linked with reward-related activity in mesocorticolimbic circuits. In healthy adults, humor processing was shown to be moderated by temperament traits like intro-/extraversion, neuroticism, or social anxiety, representing risk factors for psychopathology. However, comparable data from early developmental stages is crucially lacking. Here, we report for the first time data from 22 children (ages 6 to 13) revealing an influence of temperament on humor processing. Specifically, we assessed the effects of Emotionality, Shyness, and Sociability, which are analogous to neuroticism, behavioral inhibition/fear and extraversion in adults. We found Emotionality to be positively, but Shyness negatively associated with brain activity linked with both cognitive and emotional humor components. In addition, Shyness and Sociability were positively related to activity in the periaqueductal gray region during humor processing. These findings are of potential clinical relevance regarding the early detection of childhood psychopathology. Previous data on humor processing in both adults and children furthermore suggest that intelligence (IQ) supports incongruity detection and resolution, whereas mirth and associated brain activity diminishes with increasing age. Here, we found that increasing age and IQ were linked with stronger activity to humor in brain areas implicated in the cognitive component of humor. Such data suggest that humor processing undergoes developmental changes and is moderated by higher IQ scores, both factors likely improving incongruity detection and resolution.

Sex differences during humor appreciation in child-sibling pairs.

The developmental origin of sex differences in adult brain function is poorly understood. Elucidating neural mechanisms underlying comparable cognitive functionality in both children and adults is required to address this gap. Humor appreciation represents a particularly relevant target for such developmental research because explanatory theories apply across the life span, and underlying neurocircuitry shows sex differences in adults. As a positive mood state, humor is also of interest due to sex differences in rates of depression, a disorder afflicting twice as many women as men. In this study, we employed functional magnetic resonance imaging (fMRI) to investigate brain responses to funny versus positive (and neutral) video clips in 22 children, ages 6-13 years, including eight sibling-pairs. Our data revealed increased activity to funny clips in bilateral temporo-occipital cortex, midbrain, and amygdala in girls. Conversely, we found heightened activation to positive clips in bilateral inferior parietal lobule, fusiform gyrus, inferior frontal gyrus, amygdala, and ventromedial prefrontal cortex in boys. Many of these effects persisted when looking at sibling-pairs only. We interpret such findings as reflecting the presence of early sex divergence in reward saliency or expectation and stimulus relevance attribution. These findings are discussed in the context of evolutionary and developmental theories of humor function.

Neurobiological underpinnings of math and reading learning disabilities.

The primary goal of this review is to highlight current research and theories describing the neurobiological basis of math (MD), reading (RD), and comorbid math and reading disability (MD+RD). We first describe the unique brain and cognitive processes involved in acquisition of math and reading skills, emphasizing similarities and differences in each domain. Next we review functional imaging studies of MD and RD in children, integrating relevant theories from experimental psychology and cognitive neuroscience to characterize the functional neuroanatomy of cognitive dysfunction in MD and RD. We then review recent research on the anatomical correlates of MD and RD. Converging evidence from morphometry and tractography studies are presented to highlight distinct patterns of white matter pathways which are disrupted in MD and RD. Finally, we examine how the intersection of MD and RD provides a unique opportunity to clarify the unique and shared brain systems which adversely impact learning and skill acquisition in MD and RD, and point out important areas for future work on comorbid learning disabilities.

Topological properties of large-scale structural brain networks in children with familial risk for reading difficulties.

Developmental dyslexia is a neurobiological deficit characterized by persistent difficulty in learning to read in children and adults who otherwise possess normal intelligence. Functional and structural connectivity data suggest that developmental dyslexia could be a disconnection syndrome. However, whether abnormalities in connectivity exist in beginning readers at-risk for reading difficulties is unknown. Using graph-theoretical analysis, we investigated differences in global and regional topological properties of structural brain networks in 42 beginning readers with (FH+) and without (FH-) familial risk for reading difficulties. We constructed separate structural correlation networks based on measures of surface area and cortical thickness. Results revealed changes in topological properties in brain regions known to be abnormal in dyslexia (left supramarginal gyrus, left inferior frontal gyrus) in the FH+ group mainly in the network constructed from measures of cortical surface area. We also found alterations in topological properties in regions that are not often advertised as dyslexia but nonetheless play important role in reading (left posterior cingulate, hippocampus, and left precentral gyrus). To our knowledge, this is the first report of altered topological properties of structural correlation networks in children at risk for reading difficulty, and motivates future studies that examine the mechanisms underlying how these brain networks may mediate the influences of family history on reading outcome.