Notes from Beethoven's genome.

Rapid advances over the last decade in DNA sequencing and statistical genetics enable us to investigate the genomic makeup of individuals throughout history. In a recent notable study, Begg et al.1 used Ludwig van Beethoven's hair strands for genome sequencing and explored genetic predispositions for some of his documented medical issues. Given that it was arguably Beethoven's skills as a musician and composer that made him an iconic figure in Western culture, we here extend the approach and apply it to musicality. We use this as an example to illustrate the broader challenges of individual-level genetic predictions.

The shared genetic architecture and evolution of human language and musical rhythm.

Rhythm and language-related traits are phenotypically correlated, but their genetic overlap is largely unknown. Here, we leveraged two large-scale genome-wide association studies performed to shed light on the shared genetics of rhythm (N=606,825) and dyslexia (N=1,138,870). Our results reveal an intricate shared genetic and neurobiological architecture, and lay groundwork for resolving longstanding debates about the potential co-evolution of human language and musical traits.

Individual differences in neural markers of beat processing relate to spoken grammar skills in six-year-old children.

Based on the idea that neural entrainment establishes regular attentional fluctuations that facilitate hierarchical processing in both music and language, we hypothesized that individual differences in syntactic (grammatical) skills will be partly explained by patterns of neural responses to musical rhythm. To test this hypothesis, we recorded neural activity using electroencephalography (EEG) while children (N = 25) listened passively to rhythmic patterns that induced different beat percepts. Analysis of evoked beta and gamma activity revealed that individual differences in the magnitude of neural responses to rhythm explained variance in six-year-olds' expressive grammar abilities, beyond and complementarily to their performance in a behavioral rhythm perception task. These results reinforce the idea that mechanisms of neural beat entrainment may be a shared neural resource supporting hierarchical processing across music and language and suggest a relevant marker of the relationship between rhythm processing and grammar abilities in elementary-school-age children, previously observed only behaviorally.

Regular rhythmic primes improve sentence repetition in children with developmental language disorder.

Recently reported links between rhythm and grammar processing have opened new perspectives for using rhythm in clinical interventions for children with developmental language disorder (DLD). Previous research using the rhythmic priming paradigm has shown improved performance on language tasks after regular rhythmic primes compared to control conditions. However, this research has been limited to effects of rhythmic priming on grammaticality judgments. The current study investigated whether regular rhythmic primes could also benefit sentence repetition, a task requiring proficiency in complex syntax-an area of difficultly for children with DLD. Regular rhythmic primes improved sentence repetition performance compared to irregular rhythmic primes in children with DLD and with typical development-an effect that did not occur with a non-linguistic control task. These findings suggest processing overlap for musical rhythm and linguistic syntax, with implications for the use of rhythmic stimulation for treatment of children with DLD in clinical research and practice.

Using Motor Tempi to Understand Rhythm and Grammatical Skills in Developmental Language Disorder and Typical Language Development.

Children with developmental language disorder (DLD) show relative weaknesses on rhythm tasks beyond their characteristic linguistic impairments. The current study compares preferred tempo and the width of an entrainment region for 5- to 7-year-old typically developing (TD) children and children with DLD and considers the associations with rhythm aptitude and expressive grammar skills in the two populations. Preferred tempo was measured with a spontaneous motor tempo task (tapping tempo at a comfortable speed), and the width (range) of an entrainment region was measured by the difference between the upper (slow) and lower (fast) limits of tapping a rhythm normalized by an individual's spontaneous motor tempo. Data from N = 16 children with DLD and N = 114 TD children showed that whereas entrainment-region width did not differ across the two groups, slowest motor tempo, the determinant of the upper (slow) limit of the entrainment region, was at a faster tempo in children with DLD vs. TD. In other words, the DLD group could not pace their slow tapping as slowly as the TD group. Entrainment-region width was positively associated with rhythm aptitude and receptive grammar even after taking into account potential confounding factors, whereas expressive grammar did not show an association with any of the tapping measures. Preferred tempo was not associated with any study variables after including covariates in the analyses. These results motivate future neuroscientific studies of low-frequency neural oscillatory mechanisms as the potential neural correlates of entrainment-region width and their associations with musical rhythm and spoken language processing in children with typical and atypical language development.

Exploring individual differences in musical rhythm and grammar skills in school-aged children with typically developing language.

A growing number of studies have shown a connection between rhythmic processing and language skill. It has been proposed that domain-general rhythm abilities might help children to tap into the rhythm of speech (prosody), cueing them to prosodic markers of grammatical (syntactic) information during language acquisition, thus underlying the observed correlations between rhythm and language. Working memory processes common to task demands for musical rhythm discrimination and spoken language paradigms are another possible source of individual variance observed in musical rhythm and language abilities. To investigate the nature of the relationship between musical rhythm and expressive grammar skills, we adopted an individual differences approach in N = 132 elementary school-aged children ages 5-7, with typical language development, and investigated prosodic perception and working memory skills as possible mediators. Aligning with the literature, musical rhythm was correlated with expressive grammar performance (r = 0.41, p < 0.001). Moreover, musical rhythm predicted mastery of complex syntax items (r = 0.26, p = 0.003), suggesting a privileged role of hierarchical processing shared between musical rhythm processing and children's acquisition of complex syntactic structures. These relationships between rhythm and grammatical skills were not mediated by prosodic perception, working memory, or non-verbal IQ; instead, we uncovered a robust direct effect of musical rhythm perception on grammatical task performance. Future work should focus on possible biological endophenotypes and genetic influences underlying this relationship.

Heritability of Childhood Music Engagement and Associations with Language and Executive Function: Insights from the Adolescent Brain Cognitive Development (ABCD) Study.

Music engagement is a powerful, influential experience that often begins early in life. Music engagement is moderately heritable in adults (~ 41-69%), but fewer studies have examined genetic influences on childhood music engagement, including their association with language and executive functions. Here we explored genetic and environmental influences on music listening and instrument playing (including singing) in the baseline assessment of the Adolescent Brain Cognitive Development study. Parents reported on their 9-10-year-old children's music experiences (N = 11,876 children; N = 1543 from twin pairs). Both music measures were explained primarily by shared environmental influences. Instrument exposure (but not frequency of instrument engagement) was associated with language skills (r = .27) and executive functions (r = .15-0.17), and these associations with instrument engagement were stronger than those for music listening, visual art, or soccer engagement. These findings highlight the role of shared environmental influences between early music experiences, language, and executive function, during a formative time in development.

Confronting ethical and social issues related to the genetics of musicality.

New interdisciplinary research into genetic influences on musicality raises a number of ethical and social issues for future avenues of research and public engagement. The historical intersection of music cognition and eugenics heightens the need to vigilantly weigh the potential risks and benefits of these studies and the use of their outcomes. Here, we bring together diverse disciplinary expertise (complex trait genetics, music cognition, musicology, bioethics, developmental psychology, and neuroscience) to interpret and guide the ethical use of findings from recent and future studies. We discuss a framework for incorporating principles of ethically and socially responsible conduct of musicality genetics research into each stage of the research lifecycle: study design, study implementation, potential applications, and communication.

Exploring the genetics of rhythmic perception and musical engagement in the Vanderbilt Online Musicality Study.

Uncovering the genetic underpinnings of musical ability and engagement is a foundational step for exploring their wide-ranging associations with cognition, health, and neurodevelopment. Prior studies have focused on using twin and family designs, demonstrating moderate heritability of musical phenotypes. The current study used genome-wide complex trait analysis and polygenic score (PGS) approaches utilizing genotype data to examine genetic influences on two musicality traits (rhythmic perception and music engagement) in N = 1792 unrelated adults in the Vanderbilt Online Musicality Study. Meta-analyzed heritability estimates (including a replication sample of Swedish individuals) were 31% for rhythmic perception and 12% for self-reported music engagement. A PGS derived from a recent study on beat synchronization ability predicted both rhythmic perception (ß = 0.11) and music engagement (ß = 0.19) in our sample, suggesting that genetic influences underlying self-reported beat synchronization ability also influence individuals' rhythmic discrimination aptitude and the degree to which they engage in music. Cross-trait analyses revealed a modest contribution of PGSs from several nonmusical traits (from the cognitive, personality, and circadian chronotype domains) to individual differences in musicality (ß = -0.06 to 0.07). This work sheds light on the complex relationship between the genetic architecture of musical rhythm processing, beat synchronization, music engagement, and other nonmusical traits.

Music and verbal ability - a twin study of genetic and environmental associations.

Musical aptitude and music training are associated with language-related cognitive outcomes, even when controlling for general intelligence. However, genetic and environmental influences on these associations have not been studied, and it remains unclear whether music training can causally increase verbal ability. In a sample of 1,336 male twins, we tested the associations between verbal ability measured at time of conscription at age 18 and two music related variables: overall musical aptitude and total amount of music training before the age of 18. We estimated the amount of specific genetic and environmental influences on the association between verbal ability and musical aptitude, over and above the factors shared with general intelligence, using classical twin modelling. Further, we tested whether music training could causally influence verbal ability using a co-twin-control analysis. Musical aptitude and music training were significantly associated with verbal ability. Controlling for general intelligence only slightly attenuated the correlations. The partial association between musical aptitude and verbal ability, corrected for general intelligence, was mostly explained by shared genetic factors (50%) and non-shared environmental influences (35%). The co-twin-control-analysis gave no support for causal effects of early music training on verbal ability at age 18. Overall, our findings in a sizeable population sample converge with known associations between the music and language domains, while results from twin modelling suggested that this reflected a shared underlying aetiology rather than causal transfer.

Association of Developmental Language Disorder With Comorbid Developmental Conditions Using Algorithmic Phenotyping.

Importance: Developmental language disorder (DLD) is a common (with up to 7% prevalence) yet underdiagnosed childhood disorder whose underlying biological profile and comorbidities are not fully understood, especially at the population level. Objective: To identify clinically relevant conditions that co-occur with DLD at the population level. Design, Setting, and Participants: This case-control study used an electronic health record (EHR)-based population-level approach to compare the prevalence of comorbid health phenotypes between DLD cases and matched controls. These cases were identified using the Automated Phenotyping Tool for Identifying Developmental Language Disorder algorithm of the Vanderbilt University Medical Center EHR, and a phenome enrichment analysis was used to identify comorbidities. An independent sample was selected from the Geisinger Health System EHR to test the replication of the phenome enrichment using the same phenotyping and analysis pipeline. Data from the Vanderbilt EHR were accessed between March 2019 and October 2020, while data from the Geisinger EHR were accessed between January and March 2022. Main Outcomes and Measures: Common and rare comorbidities of DLD at the population level were identified using EHRs and a phecode-based enrichment analysis. Results: Comorbidity analysis was conducted for 5273 DLD cases (mean [SD] age, 16.8 [7.2] years; 3748 males [71.1%]) and 26 353 matched controls (mean [SD] age, 14.6 [5.5] years; 18 729 males [71.1%]). Relevant phenotypes associated with DLD were found, including learning disorder, delayed milestones, disorders of the acoustic nerve, conduct disorders, attention-deficit/hyperactivity disorder, lack of coordination, and other motor deficits. Several other health phenotypes not previously associated with DLD were identified, such as dermatitis, conjunctivitis, and weight and nutrition, representing a new window into the clinical complexity of DLD. Conclusions and Relevance: This study found both rare and common comorbidities of DLD. Comorbidity profiles may be leveraged to identify risk of additional health challenges, beyond language impairment, among children with DLD.

Using a polygenic score in a family design to understand genetic influences on musicality.

To further our understanding of the genetics of musicality, we explored associations between a polygenic score for self-reported beat synchronization ability (PGSrhythm) and objectively measured rhythm discrimination, as well as other validated music skills and music-related traits. Using family data, we were able to further explore potential pathways of direct genetic, indirect genetic (through passive gene-environment correlation) and confounding effects (such as population structure and assortative mating). In 5648 Swedish twins, we found PGSrhythm to predict not only rhythm discrimination, but also melody and pitch discrimination (betas between 0.11 and 0.16, p < 0.001), as well as other music-related outcomes (p < 0.05). In contrast, PGSrhythm was not associated with control phenotypes not directly related to music. Associations did not deteriorate within families (N = 243), implying that indirect genetic or confounding effects did not inflate PGSrhythm effects. A correlation (r = 0.05, p < 0.001) between musical enrichment of the family childhood environment and individuals' PGSrhythm, suggests gene-environment correlation. We conclude that the PGSrhythm captures individuals' general genetic musical propensity, affecting musical behavior more likely direct than through indirect or confounding effects.

Genome-wide association study of musical beat synchronization demonstrates high polygenicity.

Moving in synchrony to the beat is a fundamental component of musicality. Here we conducted a genome-wide association study to identify common genetic variants associated with beat synchronization in 606,825 individuals. Beat synchronization exhibited a highly polygenic architecture, with 69 loci reaching genome-wide significance (P < 5 × 10-8) and single-nucleotide-polymorphism-based heritability (on the liability scale) of 13%-16%. Heritability was enriched for genes expressed in brain tissues and for fetal and adult brain-specific gene regulatory elements, underscoring the role of central-nervous-system-expressed genes linked to the genetic basis of the trait. We performed validations of the self-report phenotype (through separate experiments) and of the genome-wide association study (polygenic scores for beat synchronization were associated with patients algorithmically classified as musicians in medical records of a separate biobank). Genetic correlations with breathing function, motor function, processing speed and chronotype suggest shared genetic architecture with beat synchronization and provide avenues for new phenotypic and genetic explorations.

You got rhythm, or more: The multidimensionality of rhythmic abilities.

Humans have a remarkable capacity for perceiving and producing rhythm. Rhythmic competence is often viewed as a single concept, with participants who perform more or less accurately on a single rhythm task. However, research is revealing numerous sub-processes and competencies involved in rhythm perception and production, which can be selectively impaired or enhanced. To investigate whether different patterns of performance emerge across tasks and individuals, we measured performance across a range of rhythm tasks from different test batteries. Distinct performance patterns could potentially reveal separable rhythmic competencies that may draw on distinct neural mechanisms. Participants completed nine rhythm perception and production tasks selected from the Battery for the Assessment of Auditory Sensorimotor and Timing Abilities (BAASTA), the Beat Alignment Test (BAT), the Beat-Based Advantage task (BBA), and two tasks from the Burgundy best Musical Aptitude Test (BbMAT). Principal component analyses revealed clear separation of task performance along three main dimensions: production, beat-based rhythm perception, and sequence memory-based rhythm perception. Hierarchical cluster analyses supported these results, revealing clusters of participants who performed selectively more or less accurately along different dimensions. The current results support the hypothesis of divergence of rhythmic skills. Based on these results, we provide guidelines towards a comprehensive testing of rhythm abilities, including at least three short tasks measuring: (1) rhythm production (e.g., tapping to metronome/music), (2) beat-based rhythm perception (e.g., BAT), and (3) sequence memory-based rhythm processing (e.g., BBA). Implications for underlying neural mechanisms, future research, and potential directions for rehabilitation and training programs are discussed.

Identifying a brain network for musical rhythm: A functional neuroimaging meta-analysis and systematic review.

We conducted a systematic review and meta-analysis of 30 functional magnetic resonance imaging studies investigating processing of musical rhythms in neurotypical adults. First, we identified a general network for musical rhythm, encompassing all relevant sensory and motor processes (Beat-based, rest baseline, 12 contrasts) which revealed a large network involving auditory and motor regions. This network included the bilateral superior temporal cortices, supplementary motor area (SMA), putamen, and cerebellum. Second, we identified more precise loci for beat-based musical rhythms (Beat-based, audio-motor control, 8 contrasts) in the bilateral putamen. Third, we identified regions modulated by beat based rhythmic complexity (Complexity, 16 contrasts) which included the bilateral SMA-proper/pre-SMA, cerebellum, inferior parietal regions, and right temporal areas. This meta-analysis suggests that musical rhythm is largely represented in a bilateral cortico-subcortical network. Our findings align with existing theoretical frameworks about auditory-motor coupling to a musical beat and provide a foundation for studying how the neural bases of musical rhythm may overlap with other cognitive domains.

Test of Prosody via Syllable Emphasis ("TOPsy"): Psychometric Validation of a Brief Scalable Test of Lexical Stress Perception.

Prosody perception is fundamental to spoken language communication as it supports comprehension, pragmatics, morphosyntactic parsing of speech streams, and phonological awareness. A particular aspect of prosody: perceptual sensitivity to speech rhythm patterns in words (i.e., lexical stress sensitivity), is also a robust predictor of reading skills, though it has received much less attention than phonological awareness in the literature. Given the importance of prosody and reading in educational outcomes, reliable and valid tools are needed to conduct large-scale health and genetic investigations of individual differences in prosody, as groundwork for investigating the biological underpinnings of the relationship between prosody and reading. Motivated by this need, we present the Test of Prosody via Syllable Emphasis ("TOPsy") and highlight its merits as a phenotyping tool to measure lexical stress sensitivity in as little as 10 min, in scalable internet-based cohorts. In this 28-item speech rhythm perception test [modeled after the stress identification test from Wade-Woolley (2016)], participants listen to multi-syllabic spoken words and are asked to identify lexical stress patterns. Psychometric analyses in a large internet-based sample shows excellent reliability, and predictive validity for self-reported difficulties with speech-language, reading, and musical beat synchronization. Further, items loaded onto two distinct factors corresponding to initially stressed vs. non-initially stressed words. These results are consistent with previous reports that speech rhythm perception abilities correlate with musical rhythm sensitivity and speech-language/reading skills, and are implicated in reading disorders (e.g., dyslexia). We conclude that TOPsy can serve as a useful tool for studying prosodic perception at large scales in a variety of different settings, and importantly can act as a validated brief phenotype for future investigations of the genetic architecture of prosodic perception, and its relationship to educational outcomes.

The Musical Abilities, Pleiotropy, Language, and Environment (MAPLE) Framework for Understanding Musicality-Language Links Across the Lifespan.

Using individual differences approaches, a growing body of literature finds positive associations between musicality and language-related abilities, complementing prior findings of links between musical training and language skills. Despite these associations, musicality has been often overlooked in mainstream models of individual differences in language acquisition and development. To better understand the biological basis of these individual differences, we propose the Musical Abilities, Pleiotropy, Language, and Environment (MAPLE) framework. This novel integrative framework posits that musical and language-related abilities likely share some common genetic architecture (i.e., genetic pleiotropy) in addition to some degree of overlapping neural endophenotypes, and genetic influences on musically and linguistically enriched environments. Drawing upon recent advances in genomic methodologies for unraveling pleiotropy, we outline testable predictions for future research on language development and how its underlying neurobiological substrates may be supported by genetic pleiotropy with musicality. In support of the MAPLE framework, we review and discuss findings from over seventy behavioral and neural studies, highlighting that musicality is robustly associated with individual differences in a range of speech-language skills required for communication and development. These include speech perception-in-noise, prosodic perception, morphosyntactic skills, phonological skills, reading skills, and aspects of second/foreign language learning. Overall, the current work provides a clear agenda and framework for studying musicality-language links using individual differences approaches, with an emphasis on leveraging advances in the genomics of complex musicality and language traits.

Neurophysiological Correlates of Dynamic Beat Tracking in Individuals With Williams Syndrome.

BACKGROUND: Williams syndrome (WS) is a neurodevelopmental disorder characterized by hypersociability, heightened auditory sensitivities, attention deficits, and strong musical interests despite differences in musical skills. Behavioral studies have reported that individuals with WS exhibit variable beat and rhythm perception skills. METHODS: We sought to investigate the neural basis of beat tracking in individuals with WS using electroencephalography. Twenty-seven adults with WS and 16 age-matched, typically developing control subjects passively listened to musical rhythms with accents on either the first or second tone of the repeating pattern, leading to distinct beat percepts. RESULTS: Consistent with the role of beta and gamma oscillations in rhythm processing, individuals with WS and typically developing control subjects showed strong evoked neural activity in both the beta (13-30 Hz) and gamma (31-55 Hz) frequency bands in response to beat onsets. This neural response was somewhat more distributed across the scalp for individuals with WS. Compared with typically developing control subjects, individuals with WS exhibited significantly greater amplitude of auditory evoked potentials (P1-N1-P2 complex) and modulations in evoked alpha (8-12 Hz) activity, reflective of sensory and attentional processes. Individuals with WS also exhibited markedly stable neural responses over the course of the experiment, and these responses were significantly more stable than those of control subjects. CONCLUSIONS: These results provide neurophysiological evidence for dynamic beat tracking in WS and coincide with the atypical auditory phenotype and attentional difficulties seen in this population.

Musical instrument engagement in adolescence predicts verbal ability 4 years later: A twin and adoption study.

Individual differences in music traits are heritable and correlated with the development of cognitive and communication skills, but little is known about whether diverse modes of music engagement (e.g., playing instruments vs. singing) reflect similar underlying genetic/environmental influences. Moreover, the biological etiology underlying the relationship between musicality and childhood language development is poorly understood. Here we explored genetic and environmental associations between music engagement and verbal ability in the Colorado Adoption/Twin Study of Lifespan behavioral development & cognitive aging (CATSLife). Adolescents (N = 1,684) completed measures of music engagement and intelligence at approximately age 12 and/or multiple tests of verbal ability at age 16. Structural equation models revealed that instrument engagement was highly heritable (a² = .78), with moderate heritability of singing (a² = .43) and dance engagement (a² = .66). Adolescent self-reported instrument engagement (but not singing or dance engagement) was genetically correlated with age 12 verbal intelligence and still was associated with age 16 verbal ability, even when controlling for age 12 full-scale intelligence, providing evidence for a longitudinal relationship between music engagement and language beyond shared general cognitive processes. Together, these novel findings suggest that shared genetic influences in part accounts for phenotypic associations between music engagement and language, but there may also be some (weak) direct benefits of music engagement on later language abilities. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

A neurodevelopmental disorders perspective into music, social attention, and social bonding.

Our commentary addresses how two neurodevelopmental disorders, Williams syndrome and autism spectrum disorder, provide novel insights into the credible signaling and music and social bonding hypotheses presented in the two target articles. We suggest that these neurodevelopmental disorders, characterized by atypical social communication, allow us to test hypotheses about music, social bonding, and their underlying neurobiology.