Cerebellar Neuromodulation Impacts Reading Fluency in Young Adults.

The cerebellum is traditionally associated with the control of coordinated movement, but ample evidence suggests that the cerebellum also supports cognitive processing. Consistent with this, right-lateralized posterolateral cerebellar regions are engaged during a range of reading and reading-related tasks, but the specific role of the cerebellum during reading tasks is not clear. Based on the cerebellar contribution to automatizing movement, it has been hypothesized that the cerebellum is specifically involved in rapid, fluent reading. We aimed to determine whether the right posterolateral cerebellum is a specific modulator of reading fluency or whether cerebellar modulation is broader, also impacting reading accuracy, rapid automatized naming, and general processing speed. To do this, we examined the effect of transcranial direct current stimulation (tDCS) targeting the right posterolateral cerebellum (lobules VI/VII) on single-word reading fluency, reading accuracy, rapid automatized naming, and processing speed. Young adults with typical reading development (n = 25; 15 female sex assigned at birth, 10 male sex assigned at birth, aged 18-28 years [M = 19.92 ± 2.04 years]) completed the reading and cognitive measures after 20 min of 2 mA anodal (excitatory), cathodal (inhibitory), or sham tDCS in a within-subjects design. Linear mixed effects models indicated that cathodal tDCS decreased single-word reading fluency scores (d = -0.36, p < 0.05) but did not significantly affect single-word reading accuracy, rapid automatized naming, or general processing speed measures. Our results suggest that the right posterolateral cerebellum is involved in reading fluency, consistent with a broader role of the cerebellum in fast, fluent cognition.

Processing Speed is Related to the General Psychopathology Factor in Youth.

The relationship between the p factor and cognition in youth has largely focused on general cognition (IQ) and executive functions (EF). Another cognitive construct, processing speed (PS), is dissociable from IQ and EF, but has received less research attention despite being related to many different mental health symptoms. The present sample included 795 youth, ages 11-16 from the Colorado Learning Disabilities Research Center (CLDRC) sample. Confirmatory factor analyses tested multiple p factor models, with the primary model being a second-order, multi-reporter p factor. We then tested the correlation between the p factor and a latent PS factor. There was a significant, negative correlation between the p factor and PS (r(87) = -0.42, p < .001), indicating that slower processing speed is associated with higher general mental health symptoms. This association is stronger than previously reported associations with IQ or EF. This finding was robust across models that used different raters (youth and caregiver) and modeling approaches (second-order vs. bifactor). Our findings indicate that PS is related to general psychopathology symptoms. This research points to processing speed as an important transdiagnostic construct that warrants further exploration across development.

Shared grey matter correlates of reading and attention.

Disorders of reading (developmental dyslexia) and attention (ADHD) have a high rate of comorbidity (25-40%), yet little is known about the neural underpinnings of this phenomenon. The current study investigated the shared and unique neural correlates of reading and attention in 330 typically developing children ages 8-18 from the Philadelphia Neurodevelopmental Cohort. Multiple regression analyses were used to identify regions of the brain where grey matter (GM) volume was associated with reading or attention scores (p < 0.001, cluster FDR p < 0.05). Better attention scores correlated with increased GM in the precuneus and higher reading scores were associated with greater thalamic GM. An exploratory conjunction analysis (p < 0.05, k > 239) found that GM in the caudate and precuneus correlated with both reading and attention scores. These results are consistent with a recent meta-analysis which identified GM reductions in the caudate in both dyslexia and ADHD and reveal potential shared neural correlates of reading and attention.

Compounding Effects of Domain-General Cognitive Weaknesses and Word Reading Difficulties on Anxiety Symptoms in Youth.

This study examined whether domain-general cognitive weaknesses in processing speed (PS) or executive functioning (EF) moderate the relation between word reading scores and anxiety such that lower word reading scores in combination with lower cognitive scores are associated with higher anxiety symptoms. The sample consisted of 755 youth ages 8-16 who were recruited as part of the Colorado Learning Disabilities Research Center twins study. Lower scores on PS (R2 = .007, p = .014), EF (R2 = .009, p = .006), and word reading (R2 = .006-.008, p = .010-.032) were associated with higher anxiety scores. In addition, the word reading × cognitive interactions were significant such that lower scores on PS (R2 = .010, p = .005) or EF (R2 = .013, p = .010) combined with lower word reading were associated with higher-than-expected anxiety symptoms. Results suggest that weaknesses in PS, EF, and word reading are modestly associated with higher anxiety symptoms, and these anxiety symptoms may be compounded in youth with both PS or EF weaknesses and word reading difficulties. These findings can guide assessment approaches for identifying youth with word reading challenges who may be at increased risk for anxiety.

Heritability and Clinical Characteristics of Neuropsychological Profiles in Youth With and Without Elevated ADHD Symptoms.

OBJECTIVE: In the last decade, there has been an increase in research that aims to parse heterogeneity in attention deficit hyperactivity disorder (ADHD). The current study tests heritability of latent class neuropsychological subtypes. METHOD: Latent class analysis was used to derive subtypes in a sample of school-age twins (N = 2,564) enriched for elevated ADHD symptoms. RESULTS: Five neuropsychological profiles replicated across twin 1 and twin 2 datasets. Latent class membership was heritable overall, but heritability varied by profile and was lower than heritability of ADHD status. Variability in neuropsychological performance across domains was the strongest predictor of elevated ADHD symptoms. Neuropsychological profiles showed distinct associations with age, psychiatric symptoms and reading ability. CONCLUSION: Neuropsychological profiles are associated with unique neurocognitive presentations, but are not strong candidate endophenotypes for ADHD diagnosis.

In Search of Cognitive Promotive and Protective Factors for Word Reading.

This study examined whether strong cognitive skills (i.e. vocabulary, rapid naming, verbal working memory [VWM], and processing speed [PS]) contributed to resilience in single-word reading skills in children at risk for reading difficulties because of low phonological awareness scores (PA). Promotive factors were identified by main effects and protective factors through PA x cognition interactions. This study included 1,807 children ages 8-16. As predicted, all cognitive skills were significantly related to reading, consistent with promotive effects. A significant, but small effect PA x vocabulary interaction (R2 change=.002, p=.00038) was detected but its form was not consistent with a classic protective effect. Rather, the PA x vocabulary interaction was consistent with a "skill-enhancement" pattern, such that children with strong PA and vocabulary skills had better than expected reading. This study provides a framework for reading resilience research and directs attention to promotive mechanisms underlying reading success.

How Specific Are Learning Disabilities?

Despite historical emphasis on "specific" learning disabilities (SLDs), academic skills are strongly correlated across the curriculum. Thus, one can ask how specific SLDs truly are. To answer this question, we used bifactor models to identify variance shared across academic domains (academic g), as well as variance unique to reading, mathematics, and writing. Participants were 686 children ages 8 to 16. Although the sample was overselected for learning disabilities, we intentionally included children across the full range of individual differences in this study in response to growing recognition that a dimensional, quantitative view of SLD is more accurate than a categorical view. Confirmatory factor analysis identified five academic domains (basic reading, reading comprehension, basic math, math problem-solving, and written expression); spelling clustered with basic reading and not writing. In the bifactor model, all measures loaded significantly on academic g. Basic reading and mathematics maintained variance distinct from academic g, consistent with the notion of SLDs in these domains. Writing did not maintain specific variance apart from academic g, and evidence for reading comprehension-specific variance was mixed. Academic g was strongly correlated with cognitive g (r = .72) but not identical to it. Implications for SLD diagnosis are discussed.

The Multiple Deficit Model: Progress, Problems, and Prospects.

The multiple deficit model (MDM) was proposed because the prevailing single-deficit model provided an inadequate account of atypical neuropsychological development. Across methods and levels of analysis, there has been support for the two fundamental tenets of the MDM, that multiple predictors contribute probabilistically to neurodevelopmental disorders and shared risk factors contribute to comorbidity. Diagnostically, the multiplicity of factors means that no single cognitive deficit or combination of deficits can be used to rule in or out most neurodevelopmental disorders. Challenges for the MDM are that the theory is difficult to falsify and that current cross-sectional studies cannot establish causality. Prospects for further development of the MDM include incorporating an explicit focus on promotive and protective factors and pursuing mechanistic connections between multiple factors across levels of analysis.

A Review of Online Dyslexia Learning Modules.

This paper presents a comprehensive review of publicly available online dyslexia learning modules with a particular focus on the extent to which modules address the prevalent myth that dyslexia is caused by "backwards reading." The authors conducted a systematic internet search to identify publicly available online dyslexia learning modules and coded the content across education, neurocognition, and policy disciplinary domains. We identified 18 topics across a small number (N = 14) of publicly available modules that focused on dyslexia, with only two modules directly addressing this dyslexia myth. While both identified this myth as false, neither provided information about the neurocognitive underpinnings of dyslexia to explain why this myth is false. This review will be useful for guiding further development of online dyslexia learning modules which are urgently needed due to persisting misinformation about this disorder. The coded content reviews of each module will also be beneficial for directing attention to existing resources for professional development on dyslexia.

Are there shared neural correlates between dyslexia and ADHD? A meta-analysis of voxel-based morphometry studies.

BACKGROUND: Dyslexia and Attention-deficit/hyperactivity disorder (ADHD) are highly comorbid neurodevelopmental disorders (estimates of 25-40% bidirectional comorbidity). Previous work has identified strong genetic and cognitive overlap between the disorders, but neural overlap is relatively unexplored. This study is a systematic meta-analysis of existing voxel-based morphometry studies to determine whether there is any overlap in the gray matter correlates of both disorders. METHODS: We conducted anatomic likelihood estimate (ALE) meta-analyses of voxel-based morphometry studies in which individuals with dyslexia (15 studies; 417 cases, 416 controls) or ADHD (22 studies; 898 cases, 763 controls) were compared to typically developing controls. We generated ALE maps for dyslexia vs. controls and ADHD vs. controls using more conservative (p < .001, k = 50) and more lenient (p < .005, k = 50) thresholds. To determine the overlap of gray matter correlates of dyslexia and ADHD, we examined the statistical conjunction between the ALE maps for dyslexia vs. controls and ADHD vs. controls (false discovery rate [FDR] p < .05, k = 50, 5000 permutations). RESULTS: Results showed largely distinct gray matter differences associated with dyslexia and ADHD. There was no evidence of statistically significant gray matter overlap at our conservative threshold, and only one region of overlap in the right caudate at our more lenient threshold. Reduced gray matter in the right caudate may be relevant to shared cognitive correlates in executive functioning and/or procedural learning. The more general finding of largely distinct regional differences in gray matter between dyslexia and ADHD suggests that other neuroimaging modalities may be more sensitive to overlapping neural correlates, and that current neuroimaging recruitment approaches may be hindering progress toward uncovering neural systems associated with comorbidity. CONCLUSIONS: The current study is the first to meta-analyze overlap between gray matter differences in dyslexia and ADHD, which is a critical step toward constructing a multi-level understanding of this comorbidity that spans the genetic, neural, and cognitive levels of analysis.

Understanding Comorbidity Between Specific Learning Disabilities.

Current definitions of specific learning disability (SLD) identify a heterogeneous population that includes individuals with weaknesses in reading, math, or writing, and these academic difficulties often co-occur in many of the same individuals. The Colorado Learning Disabilities Research Center (CLDRC) is an interdisciplinary, multisite research program that uses converging levels of analysis to understand the genetic and environmental etiology, neuropsychology, and developmental outcomes of SLDs in reading (RD), math (MD), and writing (WD), along with the comorbidity between these SLDs and other developmental disorders. The latest results from the CLDRC twin study suggest that shared genetic influences contribute to the significant covariance between all aspects of reading (word reading, reading fluency, and reading comprehension) and math (calculations, math fluency, and word problems), and distinct genetic or environmental influences also contribute to weaknesses in each specific academic domain. RD and MD are associated with a range of negative outcomes on both concurrent measures and measures of functional outcomes completed 5 years after the twins were first assessed. Over the next several years the CLDRC will continue to expand on this work by administering a comprehensive test battery that includes measures of all dimensions of academic achievement that are described in current definitions of SLD and incorporating these measures in new neuroimaging and molecular genetic studies.

Cross-Disorder Cognitive Impairments in Youth Referred for Neuropsychiatric Evaluation.

OBJECTIVES: Studies suggest that impairments in some of the same domains of cognition occur in different neuropsychiatric conditions, including those known to share genetic liability. Yet, direct, multi-disorder cognitive comparisons are limited, and it remains unclear whether overlapping deficits are due to comorbidity. We aimed to extend the literature by examining cognition across different neuropsychiatric conditions and addressing comorbidity. METHODS: Subjects were 486 youth consecutively referred for neuropsychiatric evaluation and enrolled in the Longitudinal Study of Genetic Influences on Cognition. First, we assessed general ability, reaction time variability (RTV), and aspects of executive functions (EFs) in youth with non-comorbid forms of attention-deficit/hyperactivity disorder (ADHD), mood disorders and autism spectrum disorder (ASD), as well as in youth with psychosis. Second, we determined the impact of comorbid ADHD on cognition in youth with ASD and mood disorders. RESULTS: For EFs (working memory, inhibition, and shifting/ flexibility), we observed weaknesses in all diagnostic groups when participants' own ability was the referent. Decrements were subtle in relation to published normative data. For RTV, weaknesses emerged in youth with ADHD and mood disorders, but trend-level results could not rule out decrements in other conditions. Comorbidity with ADHD did not impact the pattern of weaknesses for youth with ASD or mood disorders but increased the magnitude of the decrement in those with mood disorders. CONCLUSIONS: Youth with ADHD, mood disorders, ASD, and psychosis show EF weaknesses that are not due to comorbidity. Whether such cognitive difficulties reflect genetic liability shared among these conditions requires further study. (JINS, 2018, 24, 91-103).

Dispelling the Myth: Training in Education or Neuroscience Decreases but Does Not Eliminate Beliefs in Neuromyths.

Neuromyths are misconceptions about brain research and its application to education and learning. Previous research has shown that these myths may be quite pervasive among educators, but less is known about how these rates compare to the general public or to individuals who have more exposure to neuroscience. This study is the first to use a large sample from the United States to compare the prevalence and predictors of neuromyths among educators, the general public, and individuals with high neuroscience exposure. Neuromyth survey responses and demographics were gathered via an online survey hosted at TestMyBrain.org. We compared performance among the three groups of interest: educators (N = 598), high neuroscience exposure (N = 234), and the general public (N = 3,045) and analyzed predictors of individual differences in neuromyths performance. In an exploratory factor analysis, we found that a core group of 7 "classic" neuromyths factored together (items related to learning styles, dyslexia, the Mozart effect, the impact of sugar on attention, right-brain/left-brain learners, and using 10% of the brain). The general public endorsed the greatest number of neuromyths (M = 68%), with significantly fewer endorsed by educators (M = 56%), and still fewer endorsed by the high neuroscience exposure group (M = 46%). The two most commonly endorsed neuromyths across all groups were related to learning styles and dyslexia. More accurate performance on neuromyths was predicted by age (being younger), education (having a graduate degree), exposure to neuroscience courses, and exposure to peer-reviewed science. These findings suggest that training in education and neuroscience can help reduce but does not eliminate belief in neuromyths. We discuss the possible underlying roots of the most prevalent neuromyths and implications for classroom practice. These empirical results can be useful for developing comprehensive training modules for educators that target general misconceptions about the brain and learning.

Rare Copy Number Variants in NRXN1 and CNTN6 Increase Risk for Tourette Syndrome.

Tourette syndrome (TS) is a model neuropsychiatric disorder thought to arise from abnormal development and/or maintenance of cortico-striato-thalamo-cortical circuits. TS is highly heritable, but its underlying genetic causes are still elusive, and no genome-wide significant loci have been discovered to date. We analyzed a European ancestry sample of 2,434 TS cases and 4,093 ancestry-matched controls for rare (< 1% frequency) copy-number variants (CNVs) using SNP microarray data. We observed an enrichment of global CNV burden that was prominent for large (> 1 Mb), singleton events (OR = 2.28, 95% CI [1.39-3.79], p = 1.2 × 10-3) and known, pathogenic CNVs (OR = 3.03 [1.85-5.07], p = 1.5 × 10-5). We also identified two individual, genome-wide significant loci, each conferring a substantial increase in TS risk (NRXN1 deletions, OR = 20.3, 95% CI [2.6-156.2]; CNTN6 duplications, OR = 10.1, 95% CI [2.3-45.4]). Approximately 1% of TS cases carry one of these CNVs, indicating that rare structural variation contributes significantly to the genetic architecture of TS.

The developmental relationship between specific cognitive domains and grey matter in the cerebellum.

There is growing evidence that the cerebellum is involved in cognition and cognitive development, yet little is known about the developmental relationship between cerebellar structure and cognitive subdomains in children. We used voxel-based morphometry to assess the relationship between cerebellar grey matter (GM) and language, reading, working memory, executive function, and processing speed in 110 individuals aged 8-17 years from the Pediatric Imaging, Neurocognition, and Genetics (PING) Study. Further, we examined the effect of age on the relationships between cerebellar GM and cognition. Higher scores on vocabulary, reading, working memory, and set-shifting were associated with increased GM in the posterior cerebellum (lobules VI-IX), in regions which are typically engaged during cognitive tasks in healthy adults. For reading, working memory, and processing speed, the relationship between cerebellar GM and cognitive performance changed with age in specific cerebellar subregions. As in adults, posterior lobe cerebellar GM was associated with cognitive performance in a pediatric population, and this relationship mirrored the known developmental trajectory of posterior cerebellar GM. These findings provide further evidence that specific regions of the cerebellum support cognition and cognitive development, and suggest that the strength of this relationship depends on developmental stage.

Identification of Two Heritable Cross-Disorder Endophenotypes for Tourette Syndrome.

OBJECTIVE: Phenotypic heterogeneity in Tourette syndrome is partly due to complex genetic relationships among Tourette syndrome, obsessive-compulsive disorder (OCD), and attention deficit hyperactivity disorder (ADHD). Identifying symptom-based endophenotypes across diagnoses may aid gene-finding efforts. METHOD: Assessments for Tourette syndrome, OCD, and ADHD symptoms were conducted in a discovery sample of 3,494 individuals recruited for genetic studies. Symptom-level factor and latent class analyses were conducted in Tourette syndrome families and replicated in an independent sample of 882 individuals. Classes were characterized by comorbidity rates and proportion of parents included. Heritability and polygenic load associated with Tourette syndrome, OCD, and ADHD were estimated. RESULTS: The authors identified two cross-disorder symptom-based phenotypes across analyses: symmetry (symmetry, evening up, checking obsessions; ordering, arranging, counting, writing-rewriting compulsions, repetitive writing tics) and disinhibition (uttering syllables/words, echolalia/palilalia, coprolalia/copropraxia, and obsessive urges to offend/mutilate/be destructive). Heritability estimates for both endophenotypes were high and statistically significant (disinhibition factor=0.35, SE=0.03; symmetry factor=0.39, SE=0.03; symmetry class=0.38, SE=0.10). Mothers of Tourette syndrome probands had high rates of symmetry (49%) but not disinhibition (5%). Polygenic risk scores derived from a Tourette syndrome genome-wide association study (GWAS) were significantly associated with symmetry, while risk scores derived from an OCD GWAS were not. OCD polygenic risk scores were significantly associated with disinhibition, while Tourette syndrome and ADHD risk scores were not. CONCLUSIONS: The analyses identified two heritable endophenotypes related to Tourette syndrome that cross traditional diagnostic boundaries. The symmetry phenotype correlated with Tourette syndrome polygenic load and was present in otherwise Tourette-unaffected mothers, suggesting that this phenotype may reflect additional Tourette syndrome (rather than OCD) genetic liability that is not captured by traditional DSM-based diagnoses.

Cognitive Prediction of Reading, Math, and Attention: Shared and Unique Influences.

The current study tested a multiple-cognitive predictor model of word reading, math ability, and attention in a community-based sample of twins ages 8 to 16 years ( N = 636). The objective was to identify cognitive predictors unique to each skill domain as well as cognitive predictors shared among skills that could help explain their overlap and thus help illuminate the basis for comorbidity of related disorders (reading disability, math disability, and attention deficit hyperactivity disorder). Results indicated that processing speed contributes to the overlap between reading and attention as well as math and attention, whereas verbal comprehension contributes to the overlap between reading and math. There was no evidence that executive functioning skills help account for covariation among these skill domains. Instead, specific executive functions differentially related to certain outcomes (i.e., working memory to math and inhibition to attention). We explored whether the model varied in younger versus older children and found only minor differences. Results are interpreted within the context of the multiple deficit framework for neurodevelopmental disorders.

Social disinhibition is a heritable subphenotype of tics in Tourette syndrome.

OBJECTIVE: To identify heritable symptom-based subtypes of Tourette syndrome (TS). METHODS: Forty-nine motor and phonic tics were examined in 3,494 individuals (1,191 TS probands and 2,303 first-degree relatives). Item-level exploratory factor and latent class analyses (LCA) were used to identify tic-based subtypes. Heritabilities of the subtypes were estimated, and associations with clinical characteristics were examined. RESULTS: A 6-factor exploratory factor analysis model provided the best fit, which paralleled the somatotopic representation of the basal ganglia, distinguished simple from complex tics, and separated out socially disinhibited and compulsive tics. The 5-class LCA model best distinguished among the following groups: unaffected, simple tics, intermediate tics without social disinhibition, intermediate with social disinhibition, and high rates of all tic types. Across models, a phenotype characterized by high rates of social disinhibition emerged. This phenotype was associated with increased odds of comorbid psychiatric disorders, in particular, obsessive-compulsive disorder and attention-deficit/hyperactivity disorder, earlier age at TS onset, and increased tic severity. The heritability estimate for this phenotype based on the LCA was 0.53 (SE 0.08, p 1.7 × 10(-18)). CONCLUSIONS: Expanding on previous modeling approaches, a series of TS-related phenotypes, including one characterized by high rates of social disinhibition, were identified. These phenotypes were highly heritable and may reflect underlying biological networks more accurately than traditional diagnoses, thus potentially aiding future genetic, imaging, and treatment studies.

Attention Bias to Emotional Faces Varies by IQ and Anxiety in Williams Syndrome.

Individuals with Williams syndrome (WS) often experience significant anxiety. A promising approach to anxiety intervention has emerged from cognitive studies of attention bias to threat. To investigate the utility of this intervention in WS, this study examined attention bias to happy and angry faces in individuals with WS (N = 46). Results showed a significant difference in attention bias patterns as a function of IQ and anxiety. Individuals with higher IQ or higher anxiety showed a significant bias toward angry, but not happy faces, whereas individuals with lower IQ or lower anxiety showed the opposite pattern. These results suggest that attention bias interventions to modify a threat bias may be most effectively targeted to anxious individuals with WS with relatively high IQ.