Genetic covariation underlying reading, language and related measures in a sample selected for specific language impairment.

Specific language impairment is a developmental language disorder characterized by failure to develop language normally in the absence of a specific cause. Previous twin studies have documented the heritability of reading and language measures as well as the genetic correlation between those measures. This paper presents results from an alternative to the classical twin designs by estimating heritability from extended pedigrees. These pedigrees were previously studied as part of series of molecular genetic studies of specific language impairment where the strongest genetic findings were with reading phenotypes rather than language despite selecting pedigrees based on language impairments. To explore the relationship between reading and language in these pedigrees, variance components estimates of heritability of reading and language measures were conducted showing general agreement with the twin literature, as were genetics correlations between reading and language. Phonological short-term memory, phonological awareness and auditory processing were evaluated as candidate mediators of the reading-language genetic correlations. Only phonological awareness showed significant genetic correlations with all reading measures and several language measures while phonological short-term memory and auditory processing did not.

Increasing genotype-phenotype model determinism: application to bivariate reading/language traits and epistatic interactions in language-impaired families.

While advances in network and pathway analysis have flourished in the era of genome-wide association analysis, understanding the genetic mechanism of individual loci on phenotypes is still readily accomplished using genetic modeling approaches. Here, we demonstrate two novel genotype-phenotype models implemented in a flexible genetic modeling platform. The examples come from analysis of families with specific language impairment (SLI), a failure to develop normal language without explanatory factors such as low IQ or inadequate environment. In previous genome-wide studies, we observed strong evidence for linkage to 13q21 with a reading phenotype in language-impaired families. First, we elucidate the genetic architecture of reading impairment and quantitative language variation in our samples using a bivariate analysis of reading impairment in affected individuals jointly with language quantitative phenotypes in unaffected individuals. This analysis largely recapitulates the baseline analysis using the categorical trait data (posterior probability of linkage (PPL) = 80%), indicating that our reading impairment phenotype captured poor readers who also have low language ability. Second, we performed epistasis analysis using a functional coding variant in the brain-derived neurotrophic factor (BDNF) gene previously associated with reduced performance on working memory tasks. Modeling epistasis doubled the evidence on 13q21 and raised the PPL to 99.9%, indicating that BDNF and 13q21 susceptibility alleles are jointly part of the genetic architecture of SLI. These analyses provide possible mechanistic insights for further cognitive neuroscience studies based on the models developed herein.

Providing Instruction Based on Students' Learning Style Preferences Does Not Improve Learning.

Teachers commonly categorize students as visual or auditory learners. Despite a lack of empirical evidence, teaching to a student's perceived learning style remains common practice in education (Pashler et al., 2009). Having conducted an extensive review of the literature, Pashler et al. (2009) noted, "...very few studies have even used an experimental methodology capable of testing the validity of learning styles applied to education" (p. 105). Rogowsky et al. (2015) published the first study following the experimental design prescribed by Pashler et al. Focusing specifically on the visual/auditory dichotomy, Rogowsky et al. (2015) examined the extent to which learning style predicts comprehension and retention based on mode of instruction. Their study has been noted as "The only study located through the systematic literature search across six different databases and the screening of more than 1000 records that was totally aligned with Pashler's criteria" (Aslaksen and Loras, 2018, p. 3). The caveat to the 2015 study is that it was conducted with adult learners. The current study uses the same design and methodology as its predecessor, but on a school-aged population, making it the first of its kind. Consistent with earlier findings with adults, results failed to find a significant relationship between auditory or visual learning style preference and comprehension. Fifth graders with a visual learning style scored higher than those with an auditory learning style on listening and reading comprehension measures. As such, and counter to current educational beliefs and practices, teachers may actually be doing a disservice to students by using resources to determine their learning style and then tailoring the curriculum to match that learning style.

Dynamic auditory processing, musical experience and language development.

Children with language-learning impairments (LLI) form a heterogeneous population with the majority having both spoken and written language deficits as well as sensorimotor deficits, specifically those related to dynamic processing. Research has focused on whether or not sensorimotor deficits, specifically auditory spectrotemporal processing deficits, cause phonological deficit, leading to language and reading impairments. New trends aimed at resolving this question include prospective longitudinal studies of genetically at-risk infants, electrophysiological and neuroimaging studies, and studies aimed at evaluating the effects of auditory training (including musical training) on brain organization for language. Better understanding of the origins of developmental LLI will advance our understanding of the neurobiological mechanisms underlying individual differences in language development and lead to more effective educational and intervention strategies. This review is part of the INMED/TINS special issue "Nature and nurture in brain development and neurological disorders", based on presentations at the annual INMED/TINS symposium (http://inmednet.com/).

Generalization of non-linguistic auditory perceptual training to syllable discrimination.

PURPOSE: The generalization of non-linguistic auditory perceptual training to syllable discrimination was investigated in two experiments. METHODS: Participants were divided into a control and training group. Both groups came for pre and post-testing sessions spaced ten days apart. Following pre- testing, the training group also participated for five consecutive days in non-linguistic auditory perceptual training. Training was adaptive and involved active sequencing of rising and falling frequency modulated sweeps for 30 minutes per day. Sweeps were passively varied in onset frequency, duration and rate of presentation. A syllable discrimination threshold (SDT) task was used as the pre and post-test measure. In experiment 1, a /ba/-/da/ syllable continuum was used. In experiment 2, the pre-test battery was expanded to include /ba/-/da/, /ba/-/wa/, and /sa/-/sta/ syllable continua and a tone sequencing task that mimicked other parameters of training. RESULTS: Results of experiment 1 revealed that the training group had a significantly lowered (better) SDT following training as compared to the control group. The extent of training-driven perceptual gain was significantly correlated with pre-training performance. In experiment 2, training resulted in a significantly lowered SDT for /ba/-/da/, but not for the other syllables or the tone sequencing task. CONCLUSIONS: Results showed that task-specific attention drives generalization of auditory perceptual training from non-linguistic to linguistic contexts. Furthermore, individual differences in initial perceptual performance affect the degree of generalization following training.

Neural mechanisms of language-based learning impairments: insights from human populations and animal models.

The acquisition of speech perception and consequent expression of language represent fundamental aspects of human functioning. Yet roughly 7% to 8% of children who are otherwise healthy and of normal intelligence exhibit unexplained delays and impairments in acquiring these skills. Ongoing research has revealed several key features of language disability that may provide more direct insight into underlying anomalous neural functioning. For example, evidence supports a strong association between basic defects in processing rapidly changing acoustic information and emergent disruptions in speech perception, as well as cascading effects on other forms of language development (including reading). Considerable neurobiological research has thus focused on developmental factors that might deleteriously influence rapid sensory processing. Additional research focuses on mechanisms of neural plasticity, including how such brains might be "retrained" for improved processing of language. These and related findings from human clinical studies, electrophysiological studies, neuroimaging studies, and animal models are reviewed.

Infant discrimination of rapid auditory cues predicts later language impairment.

The etiology and mechanisms of specific language impairment (SLI) in children are unknown. Differences in basic auditory processing abilities have been suggested to underlie their language deficits. Studies suggest that the neuropathology, such as atypical patterns of cerebral lateralization and cortical cellular anomalies, implicated in such impairments likely occur early in life. Such anomalies may play a part in the rapid processing deficits seen in this disorder. However, prospective, longitudinal studies in infant populations that are critical to examining these hypotheses have not been done. In the study described, performance on brief, rapidly-presented, successive auditory processing and perceptual-cognitive tasks were assessed in two groups of infants: normal control infants with no family history of language disorders and infants from families with a positive family history for language impairment. Initial assessments were obtained when infants were 6-9 months of age (M=7.5 months) and the sample was then followed through age 36 months. At the first visit, infants' processing of rapid auditory cues as well as global processing speed and memory were assessed. Significant differences in mean thresholds were seen in infants born into families with a history of SLI as compared with controls. Examination of relations between infant processing abilities and emerging language through 24 months-of-age revealed that threshold for rapid auditory processing at 7.5 months was the single best predictor of language outcome. At age 3, rapid auditory processing threshold and being male, together predicted 39-41% of the variance in language outcome. Thus, early deficits in rapid auditory processing abilities both precede and predict subsequent language delays. These findings support an essential role for basic nonlinguistic, central auditory processes, particularly rapid spectrotemporal processing, in early language development. Further, these findings provide a temporal diagnostic window during which future language impairments may be addressed.

Specific language impairment in families: evidence for co-occurrence with reading impairments.

Two family aggregation studies report the occurrence and co-occurrence of oral language impairments (LIs) and reading impairments (RIs). Study 1 examined the occurrence (rate) of LI and RI in children with specific language impairment (SLI probands), a matched control group, and all nuclear family members. Study 2 included a larger sample of SLI probands, as well as their nuclear and extended family members. Probands and their family members who met specific criteria were classified as language and/or reading impaired based on current testing. In Study 1, the rates of LI and RI for nuclear family members (excluding probands) were significantly higher than those for control family members. In the SLI families, affected family members were more likely to have both LI and RI than either impairment alone. In Study 2, 68% of the SLI probands also met the diagnostic classification for RI. The language and RI rates for the other family members, excluding probands, were 25% and 23% respectively, with a high degree of co-occurrence of LI and RI (46%) in affected individuals. Significant sex ratio differences were found across generations in the families of SLI probands. There were more male than female offspring in these families, and more males than females were found to have both LIs and RIs. Results demonstrate that when LIs occur within families of SLI probands, these impairments generally co-occur with RIs. Our data are also consistent with prior findings that males show impairments more often than females.

Fast ForWord®: the birth of the neurocognitive training revolution.

In 1996, I cofounded Scientific Learning Corporation (SLC) with Drs Michael Merzenich, William Jenkins, and Steve Miller. I coined the term "Cogniceutical" to describe the new type of company we envisioned. SLC was the first company cofounded by academic scientists with the mission of building neurocognitive interventions. Fast ForWord® is the registered trade name of the platform SLC built to translate basic neuroplasticity-based training research into clinical and educational products. Fast ForWord® was the first cognitive neurotherapeutic intervention, the first to be individually adaptive in real time, the first "brain fitness" program that collected data over the Internet, and the first to use computer gaming technologies to change brains and enhance human potential. We included lofty goals in our first business plan for SLC. These included: using neuroplasticity-based training to improve language, literacy, and other academic skills; helping seniors maintain and recover function; helping people learn English as a second language; helping patient populations with neurological or mental disorders. SLC's first focus became improving language and literacy. Mike, Bill, Steve, and I began this journey together in 1994 with a laboratory-based research study that included seven children. To date, over two million children in 46 countries have used Fast ForWord® products. On any given school day, approximately 60,000 children log in to train on 1 of 10 Fast ForWord Language, Literacy, or Reading programs. We did not know at the time that we were creating what became a "disruptive innovation." This chapter chronicles this transformational journey.

Neuroplasticity-based cognitive and linguistic skills training improves reading and writing skills in college students.

This study reports an evaluation of the effect of computer-based cognitive and linguistic training on college students' reading and writing skills. The computer-based training included a series of increasingly challenging software programs that were designed to strengthen students' foundational cognitive skills (memory, attention span, processing speed, and sequencing) in the context of listening and higher level reading tasks. Twenty-five college students (12 native English language; 13 English Second Language), who demonstrated poor writing skills, participated in the training group. The training group received daily training during the spring semester (11 weeks) with the Fast ForWord Literacy (FFW-L) and upper levels of the Fast ForWord Reading series (Levels 3-5). The comparison group (n = 28) selected from the general college population did not receive training. Both the training and comparison groups attended the same university. All students took the Gates MacGinitie Reading Test (GMRT) and the Oral and Written Language Scales (OWLS) Written Expression Scale at the beginning (Time 1) and end (Time 2) of the spring college semester. Results from this study showed that the training group made a statistically greater improvement from Time 1 to Time 2 in both their reading skills and their writing skills than the comparison group. The group who received training began with statistically lower writing skills before training, but exceeded the writing skills of the comparison group after training.

Enhanced syllable discrimination thresholds in musicians.

Speech processing inherently relies on the perception of specific, rapidly changing spectral and temporal acoustic features. Advanced acoustic perception is also integral to musical expertise, and accordingly several studies have demonstrated a significant relationship between musical training and superior processing of various aspects of speech. Speech and music appear to overlap in spectral and temporal features; however, it remains unclear which of these acoustic features, crucial for speech processing, are most closely associated with musical training. The present study examined the perceptual acuity of musicians to the acoustic components of speech necessary for intra-phonemic discrimination of synthetic syllables. We compared musicians and non-musicians on discrimination thresholds of three synthetic speech syllable continua that varied in their spectral and temporal discrimination demands, specifically voice onset time (VOT) and amplitude envelope cues in the temporal domain. Musicians demonstrated superior discrimination only for syllables that required resolution of temporal cues. Furthermore, performance on the temporal syllable continua positively correlated with the length and intensity of musical training. These findings support one potential mechanism by which musical training may selectively enhance speech perception, namely by reinforcing temporal acuity and/or perception of amplitude rise time, and implications for the translation of musical training to long-term linguistic abilities.

Improving language and literacy is a matter of time.

Developmental deficits that affect speech perception increase the risk of language and literacy problems, which can lead to lowered academic and occupational accomplishment. Normal development and disorders of speech perception have both been linked to temporospectral auditory processing speed. Understanding the role of dynamic auditory processing in speech perception and language comprehension has led to the development of neuroplasticity-based intervention strategies aimed at ameliorating language and literacy problems and their sequelae.

Developmental language learning impairments.

Developmental language learning impairments (LLI) are one of the most prevalent of all developmental disabilities, can occur in children for a wide variety of reasons, and have been shown to co-occur frequently with other developmental social, emotional and behavioral disorders, as well as with academic achievement problems. Research pertaining to developmental LLI of unknown origin, with an emphasis on the continuum between oral and written language impairment, is the focus of this review. Given the complexity of language learning, research has focused on multiple levels of analysis, including linguistic, neuropsychological, genetic, neurobiological, and remediation studies. To date, the vast majority of data on LLI derive from studies focused on a single level of analysis. Although attempts have been made to integrate data across studies and multiple levels of analysis, this has proven to be problematic, given the heterogeneity of the subject populations used to study LLI, as well as the differences in ages, degree of impairment, and types of impairment included in each study. Given that LLI is a complex developmental disability, it is suggested that future research would benefit from taking a multiple levels of analysis approach with the same individuals, incorporating mathematical models designed to analyze dynamically changing complex systems, and studying individual differences in language learning, prospectively and longitudinally, throughout the most dynamic stages of the process.

The Neuropathology of Developmental Dysphasia: Behavioral, Morphological, and Physiological Evidence for a Pervasive Temporal Processing Disorder.

Over the past twenty years, Tallal and colleagues have directed their research toward defining the neuropathological mechanisms responsible for developmental dysphasia. We have hypothesized that higher level auditory processing dysfunction, which has previously been associated with developmental dysphasia, may result from more basic temporal processing deficits which interfere with the resolution of rapidly presented, brief duration stimuli. This temporal processing deficit interferes with adequate perception of specific verbal stimuli which require resolution of brief duration formant transitions, resulting in disordered language development. The temporal processing deficit occurs across multiple sensory modalities, and also affects rapid and sequential motor production skills. Despite relatively normal clinical neuroradiological examinations, in vivo morphological analysis, utilizing magnetic resonance imaging techniques for quantitative volumetric measurements of specific brain structures, has identified abnormalities in superior parietal, prefrontal, and temporal cortices, as well as diencephalic and caudate nuclei. Abnormalities in structures which are involved in multimodal processing and sensory motor integration is consistent with the behavioral profile of developmental dysphasia. Two alternative hypotheses regarding the neurophysiological basis of the multimodal temporal processing disorder include: dysfunction in specifc cellular systems which subserve rapid, transient processing; and abnormal gating of sensory relay by intralaminar and reticular thalamic nuclei.

A major susceptibility locus for specific language impairment is located on 13q21.

Children who fail to develop language normally-in the absence of explanatory factors such as neurological disorders, hearing impairment, or lack of adequate opportunity-are clinically described as having specific language impairment (SLI). SLI has a prevalence of approximately 7% in children entering school and is associated with later difficulties in learning to read. Research indicates that genetic factors are important in the etiology of SLI. Studies have consistently demonstrated that SLI aggregates in families. Increased monozygotic versus dizygotic twin concordance rates indicate that heredity, not just shared environment, is the cause of the familial clustering. We have collected five pedigrees of Celtic ancestry that segregate SLI, and we have conducted genomewide categorical linkage analysis, using model-based LOD score techniques. Analysis was conducted under both dominant and recessive models by use of three phenotypic classifications: clinical diagnosis, language impairment (spoken language quotient <85) and reading discrepancy (nonverbal IQ minus non-word reading >15). Chromosome 13 yielded a maximum multipoint LOD score of 3.92 under the recessive reading discrepancy model. Simulation to correct for multiple models and multiple phenotypes indicated that the genomewide empirical P value is <.01. As an alternative measure, we also computed the posterior probability of linkage (PPL), obtaining a PPL of 53% in the same region. One other genomic region yielded suggestive results on chromosome 2 (multipoint LOD score 2.86, genomic P value <.06 under the recessive language impairment model). Our findings underscore the utility of traditional LOD-score-based methods in finding genes for complex diseases, specifically, SLI.

Neural deficits in children with dyslexia ameliorated by behavioral remediation: evidence from functional MRI.

Developmental dyslexia, characterized by unexplained difficulty in reading, is associated with behavioral deficits in phonological processing. Functional neuroimaging studies have shown a deficit in the neural mechanisms underlying phonological processing in children and adults with dyslexia. The present study examined whether behavioral remediation ameliorates these dysfunctional neural mechanisms in children with dyslexia. Functional MRI was performed on 20 children with dyslexia (8-12 years old) during phonological processing before and after a remediation program focused on auditory processing and oral language training. Behaviorally, training improved oral language and reading performance. Physiologically, children with dyslexia showed increased activity in multiple brain areas. Increases occurred in left temporo-parietal cortex and left inferior frontal gyrus, bringing brain activation in these regions closer to that seen in normal-reading children. Increased activity was observed also in right-hemisphere frontal and temporal regions and in the anterior cingulate gyrus. Children with dyslexia showed a correlation between the magnitude of increased activation in left temporo-parietal cortex and improvement in oral language ability. These results suggest that a partial remediation of language-processing deficits, resulting in improved reading, ameliorates disrupted function in brain regions associated with phonological processing and produces additional compensatory activation in other brain regions.

Examination of potential overlap in autism and language loci on chromosomes 2, 7, and 13 in two independent samples ascertained for specific language impairment.

Specific language impairment is a neurodevelopmental disorder characterized by impairments essentially restricted to the domain of language and language learning skills. This contrasts with autism, which is a pervasive developmental disorder defined by multiple impairments in language, social reciprocity, narrow interests and/or repetitive behaviors. Genetic linkage studies and family data suggest that the two disorders may have genetic components in common. Two samples, from Canada and the US, selected for specific language impairment were genotyped at loci where such common genes are likely to reside. Significant evidence for linkage was previously observed at chromosome 13q21 in our Canadian sample (HLOD 3.56) and was confirmed in our US sample (HLOD 2.61). Using the posterior probability of linkage (PPL) to combine evidence for linkage across the two samples yielded a PPL over 92%. Two additional loci on chromosome 2 and 7 showed weak evidence for linkage. However, a marker in the cystic fibrosis transmembrane conductance regulator (7q31) showed evidence for association to SLI, confirming results from another group (O'Brien et al. 2003). Our results indicate that using samples selected for components of the autism phenotype may be a useful adjunct to autism genetics.