Left-dominance for resting-state temporal low-gamma power in children with impaired word-decoding and without comorbid ADHD.

One theory of the origins of reading disorders (i.e., dyslexia) is a language network which cannot effectively 'entrain' to speech, with cascading effects on the development of phonological skills. Low-gamma (low-γ, 30-45 Hz) neural activity, particularly in the left hemisphere, is thought to correspond to tracking at phonemic rates in speech. The main goals of the current study were to investigate temporal low-γ band-power during rest in a sample of children and adolescents with and without reading disorder (RD). Using a Bayesian statistical approach to analyze the power spectral density of EEG data, we examined whether (1) resting-state temporal low-γ power was attenuated in the left temporal region in RD; (2) low-γ power covaried with individual reading performance; (3) low-γ temporal lateralization was atypical in RD. Contrary to our expectations, results did not support the hypothesized effects of RD status and poor decoding ability on left hemisphere low-γ power or lateralization: post-hoc tests revealed that the lack of atypicality in the RD group was not due to the inclusion of those with comorbid attentional deficits. However, post-hoc tests also revealed a specific left-dominance for low-γ rhythms in children with reading deficits only, when participants with comorbid attentional deficits were excluded. We also observed an inverse relationship between decoding and left-lateralization in the controls, such that those with better decoding skills were less likely to show left-lateralization. We discuss these unexpected findings in the context of prior theoretical frameworks on temporal sampling. These results may reflect the importance of real-time language processing to evoke gamma rhythms in the phonemic range during childhood and adolescence.

A high-density EEG and structural MRI source analysis of the frequency following response to missing fundamental stimuli reveals subcortical and cortical activation to low and high frequency stimuli.

Pitch is a perceptual rather than physical phenomenon, important for spoken language use, musical communication, and other aspects of everyday life. Auditory stimuli can be designed to probe the relationship between perception and physiological responses to pitch-evoking stimuli. One technique for measuring physiological responses to pitch-evoking stimuli is the frequency following response (FFR). The FFR is an electroencephalographic (EEG) response to periodic auditory stimuli. The FFR contains nonlinearities not present in the stimuli, including correlates of the amplitude envelope of the stimulus; however, these nonlinearities remain undercharacterized. The FFR is a composite response reflecting multiple neural and peripheral generators, and their contributions to the scalp-recorded FFR vary in ill-understood ways depending on the electrode montage, stimulus, and imaging technique. The FFR is typically assumed to be generated in the auditory brainstem; there is also evidence both for and against a cortical contribution to the FFR. Here a methodology is used to examine the FFR correlates of pitch and the generators of the FFR to stimuli with different pitches. Stimuli were designed to tease apart biological correlates of pitch and amplitude envelope. FFRs were recorded with 256-electrode EEG nets, in contrast to a typical FFR setup which only contains a single active electrode. Structural MRI scans were obtained for each participant to co-register with the electrode locations and constrain a source localization algorithm. The results of this localization shed light on the generating mechanisms of the FFR, including providing evidence for both cortical and subcortical auditory sources.

The relationship between entrainment dynamics and reading fluency assessed by sensorimotor perturbation.

A consistent relationship has been found between rhythmic processing and reading skills. Impairment of the ability to entrain movements to an auditory rhythm in clinical populations with language-related deficits, such as children with developmental dyslexia, has been found in both behavioral and neural studies. In this study, we explored the relationship between rhythmic entrainment, behavioral synchronization, reading fluency, and reading comprehension in neurotypical English- and Mandarin-speaking adults. First, we examined entrainment stability by asking participants to coordinate taps with an auditory metronome in which unpredictable perturbations were introduced to disrupt entrainment. Next, we assessed behavioral synchronization by asking participants to coordinate taps with the syllables they produced while reading sentences as naturally as possible (tap to syllable task). Finally, we measured reading fluency and reading comprehension for native English and native Mandarin speakers. Stability of entrainment correlated strongly with tap to syllable task performance and with reading fluency, and both findings generalized across English and Mandarin speakers.

Bayesian Model Assessment for Jointly Modeling Multidimensional Response Data with Application to Computerized Testing.

Computerized assessment provides rich multidimensional data including trial-by-trial accuracy and response time (RT) measures. A key question in modeling this type of data is how to incorporate RT data, for example, in aid of ability estimation in item response theory (IRT) models. To address this, we propose a joint model consisting of a two-parameter IRT model for the dichotomous item response data, a log-normal model for the continuous RT data, and a normal model for corresponding paper-and-pencil scores. Then, we reformulate and reparameterize the model to capture the relationship between the model parameters, to facilitate the prior specification, and to make the Bayesian computation more efficient. Further, we propose several new model assessment criteria based on the decomposition of deviance information criterion (DIC) the logarithm of the pseudo-marginal likelihood (LPML). The proposed criteria can quantify the improvement in the fit of one part of the multidimensional data given the other parts. Finally, we have conducted several simulation studies to examine the empirical performance of the proposed model assessment criteria and have illustrated the application of these criteria using a real dataset from a computerized educational assessment program.

Development of an Abbreviated Adult Reading History Questionnaire (ARHQ-Brief) Using a Machine Learning Approach.

Several crucial reasons exist to determine whether an adult has had a reading disorder (RD) and to predict a child's likelihood of developing RD. The Adult Reading History Questionnaire (ARHQ) is among the most commonly used self-reported questionnaires. High ARHQ scores indicate an increased likelihood that an adult had RD as a child and that their children may develop RD. This study focused on whether a subset of ARHQ items (ARHQ-Brief) could be equally effective in assessing adults' reading history as the full ARHQ. We used a machine learning approach, lasso (known as L1 regularization), and identified 6 of 23 items that resulted in the ARHQ-Brief. Data from 97 adults and 47 children were included. With the ARHQ-Brief, we report a threshold of 0.323 as suitable to identify past likelihood of RD in adults with a sensitivity of 72.4% and a specificity of 81.5%. Comparison of predictive performances between ARHQ-Brief and the full ARHQ showed that ARHQ-Brief explained an additional 10%-35.2% of the variance in adult and child reading. Furthermore, we validated ARHQ-Brief's superior ability to predict reading ability using an independent sample of 28 children. We close by discussing limitations and future directions.

Transcranial direct current stimulation of cerebellum alters spiking precision in cerebellar cortex: A modeling study of cellular responses.

Transcranial direct current stimulation (tDCS) of the cerebellum has rapidly raised interest but the effects of tDCS on cerebellar neurons remain unclear. Assessing the cellular response to tDCS is challenging because of the uneven, highly stratified cytoarchitecture of the cerebellum, within which cellular morphologies, physiological properties, and function vary largely across several types of neurons. In this study, we combine MRI-based segmentation of the cerebellum and a finite element model of the tDCS-induced electric field (EF) inside the cerebellum to determine the field imposed on the cerebellar neurons throughout the region. We then pair the EF with multicompartment models of the Purkinje cell (PC), deep cerebellar neuron (DCN), and granule cell (GrC) and quantify the acute response of these neurons under various orientations, physiological conditions, and sequences of presynaptic stimuli. We show that cerebellar tDCS significantly modulates the postsynaptic spiking precision of the PC, which is expressed as a change in the spike count and timing in response to presynaptic stimuli. tDCS has modest effects, instead, on the PC tonic firing at rest and on the postsynaptic activity of DCN and GrC. In Purkinje cells, anodal tDCS shortens the repolarization phase following complex spikes (-14.7 ± 6.5% of baseline value, mean ± S.D.; max: -22.7%) and promotes burstiness with longer bursts compared to resting conditions. Cathodal tDCS, instead, promotes irregular spiking by enhancing somatic excitability and significantly prolongs the repolarization after complex spikes compared to baseline (+37.0 ± 28.9%, mean ± S.D.; max: +84.3%). tDCS-induced changes to the repolarization phase and firing pattern exceed 10% of the baseline values in Purkinje cells covering up to 20% of the cerebellar cortex, with the effects being distributed along the EF direction and concentrated in the area under the electrode over the cerebellum. Altogether, the acute effects of tDCS on cerebellum mainly focus on Purkinje cells and modulate the precision of the response to synaptic stimuli, thus having the largest impact when the cerebellar cortex is active. Since the spatiotemporal precision of the PC spiking is critical to learning and coordination, our results suggest cerebellar tDCS as a viable therapeutic option for disorders involving cerebellar hyperactivity such as ataxia.

Auditory Processing of Non-speech Stimuli by Children in Dual-Language Immersion Programs.

Perception of low-level auditory cues such as frequency modulation (FM) and rise time (RT) is crucial for development of phonemic representations, segmentation of word boundaries, and attunement to prosodic patterns in language. While learning an additional language, children may develop an increased sensitivity to these cues to extract relevant information from multiple types of linguistic input. Performance on these auditory processing tasks such as FM and RT by children learning another language is, however, unknown. Here we examine 92 English-speaking 7-8-year-olds in the U.S. and their performance in FM and RT perceptual tasks at the end of their second year in Cantonese or Spanish dual-language immersion compared to children in general English education programs. Results demonstrate that children in immersion programs have greater sensitivity to FM, but not RT, controlling for various factors. The immersion program students were also observed to have better phonological awareness performance. However, individual differences in FM sensitivity were not associated with phonological awareness, a pattern typically observed in monolinguals. These preliminary findings suggest a possible impact of formal language immersion on low-level auditory processing. Additional research is warranted to understand causal relationships and ultimate impact on language skills in multilinguals.

Development of thalamus mediates paternal age effect on offspring reading: A preliminary investigation.

The importance of (inherited) genetic impact in reading development is well established. De novo mutation is another important contributor that is recently gathering interest as a major liability of neurodevelopmental disorders, but has been neglected in reading research to date. Paternal age at childbirth (PatAGE) is known as the most prominent risk factor for de novo mutation, which has been repeatedly shown by molecular genetic studies. As one of the first efforts, we performed a preliminary investigation of the relationship between PatAGE, offspring's reading, and brain structure in a longitudinal neuroimaging study following 51 children from kindergarten through third grade. The results showed that greater PatAGE was significantly associated with worse reading, explaining an additional 9.5% of the variance after controlling for a number of confounds-including familial factors and cognitive-linguistic reading precursors. Moreover, this effect was mediated by volumetric maturation of the left posterior thalamus from ages 5 to 8. Complementary analyses indicated the PatAGE-related thalamic region was most likely located in the pulvinar nuclei and related to the dorsal attention network by using brain atlases, public datasets, and offspring's diffusion imaging data. Altogether, these findings provide novel insights into neurocognitive mechanisms underlying the PatAGE effect on reading acquisition during its earliest phase and suggest promising areas of future research.

Hair cortisol and dehydroepiandrosterone concentrations: Associations with executive function in early childhood.

Chronic stress during childhood negatively impacts cognition and physical and mental health. Exposure to stressors over time can cause hypothalamic-pituitary-adrenal (HPA) axis dysregulation, leading to abnormal stress hormone levels, which can be reflected in hair cortisol concentration (HCC) and hair dehydroepiandrosterone (DHEA) concentration. Although the use of HCC and DHEA to measure chronic stress in children is increasing, their effects on cognition (as indexed by executive function) remain unexplored. Accordingly, we aimed to investigate the associations of HCC, DHEA, and their ratio with measures of executive function (cognitive flexibility and working memory) in a sample of kindergarten children (N=100). We found that the expected negative association between HCC and working memory approached significance, and DHEA was significantly and positively related to cognitive flexibility. We discuss possible interpretations of our findings. Our results suggest promising areas for future investigation and encourage further exploration into HCC and DHEA as measures of chronic stress.

Maternal cerebellar gray matter volume is associated with daughters' psychotic experience.

AIM: A substantial portion of children and adolescents show subthreshold psychotic symptoms called psychotic experience (PE). Because PE shares its biological and environmental risk factors with psychotic spectrum disorders, parental neuroanatomical variation could reflect a heritable biological underpinning of PE that may predict an offspring's PE. METHODS: A total of 94 participants from 35 families without a diagnosis of major neuropsychiatric disorders were examined, including 14 mother-daughter, 17 mother-son, 12 father-daughter, and 16 father-son dyads. An offspring's PE was assessed with the Atypicality subscale of the Behavior Assessment System for Children - 2nd Edition, Self-Report of Personality form (BASCaty). We examined correlations between voxel-by-voxel parental gray matter volume and their offspring's BASCaty score. RESULTS: Maternal cerebellar gray matter volume using voxel-based morphometry was positively correlated with their daughters' BASCaty scores. The findings were significant in a more robust approach using cerebellum-specific normalization known. We did not find significant correlation between paternal gray matter volume and BASCaty scores or between offspring gray matter volumes and their BASCaty scores. CONCLUSION: Expanding upon parent-of-origin effects in psychosis, maternal neuroanatomical variation was associated with daughters' PE. The nature of this sex-specific intergenerational effect is unknown, but maternally transmitted genes may relate cerebellum development to PE pathogenesis.

Spoken language proficiency predicts print-speech convergence in beginning readers.

Learning to read transforms the brain, building on children's existing capacities for language and visuospatial processing. In particular, the development of print-speech convergence, or the spatial overlap of neural regions necessary for both auditory and visual language processing, is critical for literacy acquisition. Print-speech convergence is a universal signature of proficient reading, yet the antecedents of this convergence remain unknown. Here we examine the relationship between spoken language proficiency and the emergence of the print-speech network in beginning readers (ages 5-6). Results demonstrate that children's language proficiency, but not their early literacy skill, explains variance in their print-speech neural convergence in kindergarten. Furthermore, print-speech convergence in kindergarten predicts reading abilities one year later. These findings suggest that children's language ability is a core mechanism guiding the neural plasticity for learning to read, and extend theoretical perspectives on language and literacy acquisition across the lifespan.

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.

GABA editing with macromolecule suppression using an improved MEGA-SPECIAL sequence.

PURPOSE: The most common γ-aminobutyric-acid (GABA) editing approach, MEGA-PRESS, uses J-editing to measure GABA distinct from larger overlapping metabolites, but suffers contamination from coedited macromolecules (MMs) comprising 40 to 60% of the observed signal. MEGA-SPECIAL is an alternative method with better MM suppression, but is not widely used primarily because of its relatively poor spatial localization. Our goal was to develop an improved MM-suppressed GABA editing sequence at 3 Tesla. METHODS: We modified a single-voxel MEGA-SPECIAL sequence with an oscillating readout gradient for improved spatial localization, and used very selective 30-ms editing pulses for improved suppression of coedited MMs. RESULTS: Simulation and in vivo experiments confirmed excellent MM suppression, insensitive to the range of B0 frequency drifts typically encountered in vivo. Both intersubject and intrasubject studies showed that MMs, when suppressed by the improved MEGA-SPECIAL method, contributed approximately 40% to the corresponding MEGA-PRESS measurements. From the intersubject study, the coefficient of variation for GABA+/Cre (MEGA-PRESS) was 11.2% versus 7% for GABA/Cre (improved MEGA-SPECIAL), demonstrating significantly reduced variance (P = 0.005), likely coming from coedited MMs. CONCLUSIONS: This improved MEGA-SPECIAL sequence provides unbiased GABA measurements with reduced variance as compared with conventional MEGA-PRESS. This approach is also relatively insensitive to the range of B0 drifts typically observed in in vivo human studies. Magn Reson Med 79:41-47, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

Neurobiological bases of reading disorder Part I: Etiological investigations.

While many studies have focused on identifying the neural and behavioral characteristics of decoding-based reading disorder (RD, aka developmental dyslexia), the etiology of RD remains largely unknown and understudied. Because the brain plays an intermediate role between genetic factors and behavioral outcomes, it is promising to address causality from a neural perspective. In the current, Part I of the two-part review, we discuss neuroimaging approaches to addressing the causality issue and review the results of studies that have employed these approaches. We assume that if a neural signature were associated with RD etiology, it would (a) manifest across comparisons in different languages, (b) be experience independent and appear in comparisons between RD and reading-matched controls, (c) be present both pre- and post-intervention, (d) be found in at-risk, pre-reading children and (e) be associated with genetic risk. We discuss each of these five characteristics in turn and summarize the studies that have examined each of them. The available literature provides evidence that anomalies in left temporo-parietal cortex, and possibly occipito-temporal cortex, may be closely related to the etiology of RD. Improved understanding of the etiology of RD can help improve the accuracy of early detection and enable targeted intervention of cognitive processes that are amenable to change, leading to improved outcomes in at-risk or affected populations.

Neural Noise Hypothesis of Developmental Dyslexia.

Developmental dyslexia (decoding-based reading disorder; RD) is a complex trait with multifactorial origins at the genetic, neural, and cognitive levels. There is evidence that low-level sensory-processing deficits precede and underlie phonological problems, which are one of the best-documented aspects of RD. RD is also associated with impairments in integrating visual symbols with their corresponding speech sounds. Although causal relationships between sensory processing, print-speech integration, and fluent reading, and their neural bases are debated, these processes all require precise timing mechanisms across distributed brain networks. Neural excitability and neural noise are fundamental to these timing mechanisms. Here, we propose that neural noise stemming from increased neural excitability in cortical networks implicated in reading is one key distal contributor to RD.

Possible roles for fronto-striatal circuits in reading disorder.

Several studies have reported hyperactivation in frontal and striatal regions in individuals with reading disorder (RD) during reading-related tasks. Hyperactivation in these regions is typically interpreted as a form of neural compensation related to articulatory processing. Fronto-striatal hyperactivation in RD could however, also arise from fundamental impairment in reading related processes, such as phonological processing and implicit sequence learning relevant to early language acquisition. We review current evidence for the compensation hypothesis in RD and apply large-scale reverse inference to investigate anatomical overlap between hyperactivation regions and neural systems for articulation, phonological processing, implicit sequence learning. We found anatomical convergence between hyperactivation regions and regions supporting articulation, consistent with the proposed compensatory role of these regions, and low convergence with phonological and implicit sequence learning regions. Although the application of large-scale reverse inference to decode function in a clinical population should be interpreted cautiously, our findings suggest future lines of research that may clarify the functional significance of hyperactivation in RD.

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.

Shared temporoparietal dysfunction in dyslexia and typical readers with discrepantly high IQ.

It is currently believed that reading disability (RD) should be defined by reading level without regard to broader aptitude (IQ). There is debate, however, about how to classify individuals who read in the typical range but less well than would be expected by their higher IQ. We used functional magnetic resonance imaging (fMRI) in 49 children to examine whether those with typical, but discrepantly low reading ability relative to IQ, show dyslexia-like activation patterns during reading. Children who were typical readers with high-IQ discrepancy showed reduced activation in left temporoparietal neocortex relative to two control groups of typical readers without IQ discrepancy. This pattern was consistent and spatially overlapping with results in children with RD compared to typically reading children. The results suggest a shared neurological atypicality in regions associated with phonological processing between children with dyslexia and children with typical reading ability that is substantially below their IQ.

Universal brain signature of proficient reading: Evidence from four contrasting languages.

We propose and test a theoretical perspective in which a universal hallmark of successful literacy acquisition is the convergence of the speech and orthographic processing systems onto a common network of neural structures, regardless of how spoken words are represented orthographically in a writing system. During functional MRI, skilled adult readers of four distinct and highly contrasting languages, Spanish, English, Hebrew, and Chinese, performed an identical semantic categorization task to spoken and written words. Results from three complementary analytic approaches demonstrate limited language variation, with speech-print convergence emerging as a common brain signature of reading proficiency across the wide spectrum of selected languages, whether their writing system is alphabetic or logographic, whether it is opaque or transparent, and regardless of the phonological and morphological structure it represents.