Genome-wide analyses of individual differences in quantitatively assessed reading- and language-related skills in up to 34,000 people.

The use of spoken and written language is a fundamental human capacity. Individual differences in reading- and language-related skills are influenced by genetic variation, with twin-based heritability estimates of 30 to 80% depending on the trait. The genetic architecture is complex, heterogeneous, and multifactorial, but investigations of contributions of single-nucleotide polymorphisms (SNPs) were thus far underpowered. We present a multicohort genome-wide association study (GWAS) of five traits assessed individually using psychometric measures (word reading, nonword reading, spelling, phoneme awareness, and nonword repetition) in samples of 13,633 to 33,959 participants aged 5 to 26 y. We identified genome-wide significant association with word reading (rs11208009, P = 1.098 × 10-8) at a locus that has not been associated with intelligence or educational attainment. All five reading-/language-related traits showed robust SNP heritability, accounting for 13 to 26% of trait variability. Genomic structural equation modeling revealed a shared genetic factor explaining most of the variation in word/nonword reading, spelling, and phoneme awareness, which only partially overlapped with genetic variation contributing to nonword repetition, intelligence, and educational attainment. A multivariate GWAS of word/nonword reading, spelling, and phoneme awareness maximized power for follow-up investigation. Genetic correlation analysis with neuroimaging traits identified an association with the surface area of the banks of the left superior temporal sulcus, a brain region linked to the processing of spoken and written language. Heritability was enriched for genomic elements regulating gene expression in the fetal brain and in chromosomal regions that are depleted of Neanderthal variants. Together, these results provide avenues for deciphering the biological underpinnings of uniquely human traits.

Finding Pattern in the Noise: Persistent Implicit Statistical Knowledge Impacts the Processing of Unpredictable Stimuli.

Humans can extract statistical regularities of the environment to predict upcoming events. Previous research recognized that implicitly acquired statistical knowledge remained persistent and continued to influence behavior even when the regularities were no longer present in the environment. Here, in an fMRI experiment, we investigated how the persistence of statistical knowledge is represented in the brain. Participants (n = 32) completed a visual, four-choice, RT task consisting of statistical regularities. Two types of blocks constantly alternated with one another throughout the task: predictable statistical regularities in one block type and unpredictable ones in the other. Participants were unaware of the statistical regularities and their changing distribution across the blocks. Yet, they acquired the statistical regularities and showed significant statistical knowledge at the behavioral level not only in the predictable blocks but also in the unpredictable ones, albeit to a smaller extent. Brain activity in a range of cortical and subcortical areas, including early visual cortex, the insula, the right inferior frontal gyrus, and the right globus pallidus/putamen contributed to the acquisition of statistical regularities. The right insula, inferior frontal gyrus, and hippocampus as well as the bilateral angular gyrus seemed to play a role in maintaining this statistical knowledge. The results altogether suggest that statistical knowledge could be exploited in a relevant, predictable context as well as transmitted to and retrieved in an irrelevant context without a predictable structure.

Genome-wide association study reveals new insights into the heritability and genetic correlates of developmental dyslexia.

Developmental dyslexia (DD) is a learning disorder affecting the ability to read, with a heritability of 40-60%. A notable part of this heritability remains unexplained, and large genetic studies are warranted to identify new susceptibility genes and clarify the genetic bases of dyslexia. We carried out a genome-wide association study (GWAS) on 2274 dyslexia cases and 6272 controls, testing associations at the single variant, gene, and pathway level, and estimating heritability using single-nucleotide polymorphism (SNP) data. We also calculated polygenic scores (PGSs) based on large-scale GWAS data for different neuropsychiatric disorders and cortical brain measures, educational attainment, and fluid intelligence, testing them for association with dyslexia status in our sample. We observed statistically significant (p < 2.8 × 10-6) enrichment of associations at the gene level, for LOC388780 (20p13; uncharacterized gene), and for VEPH1 (3q25), a gene implicated in brain development. We estimated an SNP-based heritability of 20-25% for DD, and observed significant associations of dyslexia risk with PGSs for attention deficit hyperactivity disorder (at pT = 0.05 in the training GWAS: OR = 1.23[1.16; 1.30] per standard deviation increase; p = 8 × 10-13), bipolar disorder (1.53[1.44; 1.63]; p = 1 × 10-43), schizophrenia (1.36[1.28; 1.45]; p = 4 × 10-22), psychiatric cross-disorder susceptibility (1.23[1.16; 1.30]; p = 3 × 10-12), cortical thickness of the transverse temporal gyrus (0.90[0.86; 0.96]; p = 5 × 10-4), educational attainment (0.86[0.82; 0.91]; p = 2 × 10-7), and intelligence (0.72[0.68; 0.76]; p = 9 × 10-29). This study suggests an important contribution of common genetic variants to dyslexia risk, and novel genomic overlaps with psychiatric conditions like bipolar disorder, schizophrenia, and cross-disorder susceptibility. Moreover, it revealed the presence of shared genetic foundations with a neural correlate previously implicated in dyslexia by neuroimaging evidence.

Lexical Competition Without Phonology: Masked Orthographic Neighbor Priming With Deaf Readers.

Skilled reading is thought to rely on well-specified lexical representations that compete during visual word recognition. The establishment of these lexical representations is assumed to be driven by phonology. To test the role of phonology, we examined the prime lexicality effect (PLE), the index of lexical competition in signing deaf (N = 28) and hearing (N = 28) adult readers of Hungarian matched in age and education. We found no PLE for deaf readers even when reading skills were controlled for. Surprisingly, the hearing controls also showed reduced PLE; however, the effect was modulated by reading skill. More skilled hearing readers showed PLE, while more skilled deaf readers did not. These results suggest that phonology contributes to lexical competition; however, high-quality lexical representations are not necessarily built through phonology in deaf readers.

Orthographic-Phonological Mapping and the Emergence of Visual Expertise for Print: A Developmental Event-Related Potential Study.

The N1 effect is an electrophysiological marker of visual specialization for print. The phonological mapping hypothesis (Maurer & McCandliss, 2007) posits that the left-lateralized effect reflects grapheme-phoneme integration. In this event-related potential study, first (age = 7.06 years, N = 32) and third-grade readers (age = 9.29 years, N = 28) were presented with pairs of pseudowords and Armenian character strings in a novel implicit same-different paradigm. To test the phonological mapping hypothesis, stimuli were presented in visual-only and audiovisual conditions. The results demonstrated that tuning for print already emerges in first grade. Moreover, the parallel presentation of auditory stimuli enhanced the N1 effect suggesting a role of orthographic-phonological mapping in the development of specialization for print.

Tracking the implicit acquisition of nonadjacent transitional probabilities by ERPs.

The implicit acquisition of complex probabilistic regularities has been found to be crucial in numerous automatized cognitive abilities, including language processing and associative learning. However, it has not been completely elucidated how the implicit extraction of second-order nonadjacent transitional probabilities is reflected by neurophysiological processes. Therefore, this study investigated the sensitivity of event-related brain potentials (ERPs) to these probabilistic regularities embedded in a sequence of visual stimuli without providing explicit information on the structure of the stimulus stream. Healthy young adults (N = 32) performed a four-choice RT task that included a sequential regularity between nonadjacent trials yielding a complex transitional probability structure. ERPs were measured relative to both stimulus and response onset. RTs indicated the rapid acquisition of the sequential regularity and the transitional probabilities. The acquisition process was also tracked by the stimulus-locked and response-locked P3 component: The P3 peak was larger for the sequence than for the random stimuli, while the late P3 was larger for less probable than for more probable short-range relations among the random stimuli. According to the RT and P3 effects, sensitivity to the sequential regularity is assumed to be supported by the initial sensitivity to the transitional probabilities. These results suggest that stimulus-response contingencies on the probabilistic regularities of the ongoing stimulus context are implicitly mapped and constantly revised. Overall, this study (1) highlights the role of predictive processes during implicit memory formation, and (2) delineates a potential to gain further insight into the dynamics of implicit acquisition processes.

Adaptive specialization in position encoding while learning to read.

The present experiments focused on how orthographic processing develops during reading acquisition. Specifically, a large, cross-sectional sample of children from grade 2 to grade 4 was exposed to pairs of words, pseudowords, digit strings, and pseudo-letter (Armenian) strings while their sensitivity to transpositions (T) and substitutions (S) of internal characters was investigated in a perceptual matching task. The results showed that the development of identity and position decoding diverged between the four stimulus categories. Most importantly, sensitivity improved with longer exposure to formal education and higher reading level to both S and T pairs for digit strings, but only to S pairs for words and pseudowords. The results were successfully reproduced in two small independent samples. We propose a general framework, the Adaptive Specialization Hypothesis, to accommodate the results. According to this hypothesis, the transposed-letter effect is not a hard-wired feature of the orthographic processing system but an adaptive response of the developing orthographic system to the constraints of lexical access in several orthographies.

The role of cognitive control and naming in aphasia.

The classical aphasia literature has placed considerable emphasis on the language-centered understanding of aphasia and failed to consider the role of executive functions (EFs) regarding different aspects of patients' performance. Many current studies suggest deficits in EFs in individuals with aphasia, however, the available data is still limited. Here, our aim was to investigate the impairment of EFs and its potential negative effects on naming (slower performance, increased reaction time and/or decreased accuracy). We sought to determine whether the poor performance observed in word fluency task correlated with similar outcomes in naming. Our study involved five Hungarian post stroke aphasic patients (2 males and 3 females) between the ages of 60 and 70, as well as a control group matched for age and gender. The participants were diagnosed with different types of aphasia (global, Wernicke's, anomic and conduction). This study employed various neuropsychological and linguistic batteries. By comparing the patients' performance to that of the control group, we aimed to investigate the impacts of stroke. Within the aphasia group, we observed difficulties in following complex commands and a connection between general slowness and reduced accuracy in naming. We concluded that impairment of executive functions may have a negative impact on naming, comprehension, and fluency. Therefore, it is important to consider functional variations in neural networks, and to base our interpretations on the available psychophysiological data in literature. Our findings provide an alternative perspective to the traditional assessment of aphasia and highlight the importance of considering the role of executive functions.

From psychophysiology to brain imaging: forty-five years MMN history of investigating acoustic change sensitivity.

Forty-five years have passed since the first publication of the mismatch negativity (MMN) event-related brain potential (ERP) component. The first 10 years of research hardly gained any particular attention of the scientific community interested in acoustic perception. Debates on the nature of sensation versus perception were going on, and the technical possibilities to record ERPs, called in general evoked potentials, were very limited. Subtle changes in pure tone frequency or intensity giving rise to the MMN component were first investigated in humans. The background of the theoretical model developed by Risto Näätänen was the orientation reaction model of E.N. Sokolov published in 1963 so that the MMN was seen first as an electrophysiological correlate of auditory change detection. This fundamental ability of the auditory system seen as crucial for survival led to the development of the first animal model of the MMN (Csépe et al. in Clin Neurophysiol 66: 571-578, 1987). Indeed, it was confirmed that the MMN was the brain correlate of subtle changes detected that might alert to potential threats in the environment and direct the behavioral orientation. The investigations performed after 2000 introduced complex models and more sophisticated methods, both in animal and human studies, so that the MMN method was on the way to become a tool on the first place and not the main goal of research. This approach was further strengthened by the increasing number of studies on different clinical populations aiming at future applications. The aim of our review is to describe and redefine what the MMN may reflect in auditory perception and to show why and how this brain correlate of changes in the auditory scene can be used as a valuable tool in cognitive neuroscience research. We refer to publications selected to underly the argument the MMN cannot be classified anymore as a sign of simple change detection and not all the indicators used to confirm how genuine the MMN elicited by variations of tones are valid for those to  speech contrasts. We provide a fresh view on the broadly used MMN models, provided by some influential publications as well as on the unwritten history of MMN research aiming to give revised picture on what the MMN may truly reflect. We show how the focus and terminology of the MMN research have changed and what kind of misunderstandings and seemingly contradictive results prevent the MMN community to accept a generally usable cognitive model.

Investigating the neurocognitive background of speech perception with a fast multi-feature MMN paradigm.

The speech multi-feature MMN (Mismatch Negativity) offers a means to explore the neurocognitive background of the processing of multiple speech features in a short time, by capturing the time-locked electrophysiological activity of the brain known as event-related brain potentials (ERPs). Originating from Näätänen et al. (Clin Neurophysiol 115:140-144, 2004) pioneering work, this paradigm introduces several infrequent deviant stimuli alongside standard ones, each differing in various speech features. In this study, we aimed to refine the multi-feature MMN paradigm used previously to encompass both segmental and suprasegmental (prosodic) features of speech. In the experiment, a two-syllable long pseudoword was presented as a standard, and the deviant stimuli included alterations in consonants (deviation by place or place and mode of articulation), vowels (deviation by place or mode of articulation), and stress pattern in the first syllable of the pseudoword. Results indicated the emergence of MMN components across all segmental and prosodic contrasts, with the expected fronto-central amplitude distribution. Subsequent analyses revealed subtle differences in MMN responses to the deviants, suggesting varying sensitivity to phonetic contrasts. Furthermore, individual differences in MMN amplitudes were noted, partially attributable to participants' musical and language backgrounds. These findings underscore the utility of the multi-feature MMN paradigm for rapid and efficient investigation of the neurocognitive mechanisms underlying speech processing. Moreover, the paradigm demonstrated the potential to be used in further research to study the speech processing abilities in various populations.