The research, led by Roberta Bianco from the Italian Institute of Technology and her international team, sought to address a longstanding question in cognitive neuroscience: are our abilities to anticipate rhythmic and melodic structures in music innate, or are they primarily learned? While humans universally anticipate elements like beat drops or melodic shifts in songs, the developmental origins of these skills have remained elusive. Previous evidence suggested fetuses respond to music in utero through heart rate and movement changes by about 35 weeks gestation, but whether newborns possess anticipatory musical cognition was unknown.

To delve into this mystery, the researchers designed a meticulous experimental study involving 49 sleeping newborns who were exposed to the piano compositions of J.S. Bach. These included 10 original melodies characterized by consistent rhythmic and melodic structures, alongside four “scrambled” versions where melodies were intentionally disrupted by pitch shuffling. Throughout the listening sessions, the infants’ brain activity was monitored using electroencephalography (EEG), a non-invasive method employing electrodes placed carefully on their scalps to measure neuronal responses with millisecond precision.

The crux of the investigation centered on identifying neural markers of surprise, which would indicate that a newborn’s brain had formed an expectation about the musical sequence and detected a deviation. Remarkably, the babies exhibited strong neural signs of surprise when rhythmic patterns were unexpectedly altered. This indicates that even at such an early developmental stage, human infants are equipped to anticipate and internally model rhythmic structures. The presence of these expectations at birth implies that rhythmic processing is part of an intrinsic biological toolkit rather than exclusively a learned ability.

Conversely, the study found no comparable evidence that the infants formed expectations based on melody. The scrambled melodies that disrupted pitch and melodic continuity failed to elicit surprise signals in the newborn brainwaves. This suggests that the cognitive mechanisms underlying melodic anticipation are immature or absent at birth and likely develop gradually as infants gain auditory experience postnatally. Such differential development between rhythm and melody challenges assumptions that these components of musicality evolve in tandem.

These findings align intriguingly with previous observations in non-human primates, which have demonstrated rhythmic, but not melodic, processing capabilities. This similarity supports the hypothesis of evolutionary conservation in the neural architecture for rhythm perception, underscoring rhythm’s foundational role in communication and sensory processing. Melodic expectation, on the other hand, seems to be a more specialized human capacity dependent on cultural and environmental exposure during infancy and early childhood.

Beyond enriching the scientific understanding of innate human abilities, this study holds significant implications for multiple fields. From a biological perspective, clarifying how auditory systems develop rhythmic sensitivity can inform the diagnosis and treatment of developmental disorders related to auditory processing. Clinically, it might guide strategies for early interventions in infants at risk of language or cognitive delays, given the close relationship between rhythm processing and linguistic abilities.

On the educational and parenting front, the research invites reconsideration of how musical exposure during gestation and early infancy might shape neural development. The authors propose future investigations to explore how prenatal music stimulation influences the acquisition of rhythm and melody perception. If rhythm is indeed an innate foundation, systematic exposure to melodies might accelerate melodic learning and foster broader cognitive benefits, highlighting the potential for music-based enrichment programs in early childhood.

Importantly, the study underscores a nuanced distinction: newborns are “ready for Bach” in their ability to anticipate rhythmic sequences but are not yet equipped to predict melodic progressions. This duality posits rhythm as a shared human biological feature present at birth, while melodic expectation emerges through interaction with the auditory environment. Such insights challenge simplistic views of music cognition and emphasize the layered, developmental nature of musicality.

Methodologically, the use of EEG to detect prediction errors in sleeping newborns exemplifies the innovative approaches enabling deep exploration of infant cognition without reliance on behavioral responses. By interpreting subtle neural deviations signaling surprise, researchers can infer complex perceptual and cognitive states even in populations with limited communicative capacity. This technology opens doors for multidisciplinary research on development, cognition, and sensory integration.

This international collaborative effort was supported by European Union funding through Marie Skłodowska-Curie Actions and the European Research Council, alongside grants from the Hungarian National Research Development and Innovation Office. The research team comprised experts from Italy, Hungary, and Germany, reflecting the growing trend of cross-border scientific endeavors addressing fundamental questions about human nature.

Despite the profound implications, the study acknowledges limitations such as the relatively small sample size and the constraints of testing sleeping infants, which may influence the generalizability of results. Further research with larger cohorts and varying developmental stages is necessary to comprehensively map the timeline of melodic skill acquisition and unravel the environmental factors that contribute to this process.

In sum, this pioneering investigation delineates a critical boundary in newborn musical cognition: a robust, biologically embedded capacity for rhythmic prediction contrasts with an initially absent yet gradually acquired melodic expectation. This paradigm shapes our understanding of how humans enter the world as rhythmically attuned beings poised to learn and appreciate melody through experience, ultimately enriching the tapestry of musical engagement that defines human culture.

Subject of Research: People

Article Title: Human newborns form musical predictions based on rhythmic but not melodic structure

News Publication Date: February 5, 2026

Web References:

• DOI: 10.1371/journal.pbio.3003600
• Marie Skłodowska-Curie Actions: https://marie-sklodowska-curie-actions.ec.europa.eu/
• European Research Council: https://erc.europa.eu/homepage
• Hungarian National Research Development and Innovation Office: https://nkfih.gov.hu/english-nkfih

References:
Bianco R, Tóth B, Bigand F, Nguyen T, Sziller I, Háden GP, et al. (2026) Human newborns form musical predictions based on rhythmic but not melodic structure. PLoS Biol 24(2): e3003600.

Image Credits: Diego Perez-Lopez, PLOS, CC-BY 4.0

Keywords: newborn, rhythm perception, melody, music cognition, electroencephalography, musical prediction, infant brain development, auditory neuroscience, prenatal music exposure, cognitive neuroscience, early development, neural surprise

Neurodevelopment is an intricate process orchestrated by a complex interplay of genetic and environmental factors, yet pinpointing the precise molecular contributors to disorders such as microcephaly, intellectual disability, and autism spectrum disorders has proven challenging. The researchers approached this challenge by introducing CRISPR-Cas9-mediated gene knockouts across the genome in pluripotent stem cells induced to differentiate into neurons. This high-throughput functional genomics platform enabled an unprecedented interrogation of gene function during critical windows of neuronal lineage commitment and maturation, thereby revealing which genes are indispensable at various stages of neural development.

What emerged from the screen was a long list of essential genes, spanning a wide array of biological processes. Intriguingly, the vast majority of these genes had not been previously linked to human NDDs, highlighting significant gaps in the current genetic landscape associated with brain developmental anomalies. The study further stratified these essential genes based on patterns of inheritance seen in NDDs. Dominant disease-associated genes were enriched in transcriptional regulators—genes that modulate the expression of numerous downstream targets central to neuronal fate decisions. In contrast, recessive NDD genes were predominantly implicated in metabolic pathways, underscoring the diverse biological routes that can culminate in neurodevelopmental pathology.

To experimentally validate the functional relevance of their screen, the authors generated mouse knockout models for eight candidate genes identified as essential in neural differentiation: Eml1, Dusp26, Dynlrb2, Mta3, Peds1, Sgms1, Slitrk4, and Vamp3. These mouse models displayed profound neuroanatomical abnormalities, including microcephaly—a condition characterized by reduced brain size—that served as a phenotypic hallmark for half the knockout lines. These in vivo phenotypes provided compelling evidence that disruption of these genes perturbs neural development at the organismal level, reinforcing the potential clinical relevance of these findings.

Among the standout discoveries was the identification of PEDS1, a critical enzyme involved in plasmalogen biosynthesis, a lipid pathway essential for membrane integrity and signaling in neurons. Loss-of-function mutations in PEDS1 have hitherto not been associated with neurodevelopmental disorders, yet this study uncovered a bi-allelic variant in individuals exhibiting classical features of NDDs, including microcephaly, global developmental delay, and congenital cataracts. This crucial link between PEDS1 mutations and human disease exemplifies the translational power of the CRISPR screening approach combined with patient genetic analyses.

Delving deeper into the role of PEDS1, the study analyzed its deficiency in the mouse model, revealing accelerated cell-cycle exit among neural progenitors, a phenomenon that prematurely halts proliferation. This accelerated exit compromises the pool of progenitor cells available for proper neuronal differentiation and migration, ultimately yielding profound defects in brain architecture. These findings underscore the importance of precise regulation of the cell cycle and lipid metabolism during brain development—a complex choreography disrupted in PEDS1 deficiency.

The role of plasmalogens, as dictated by PEDS1 activity, extends beyond structural functions to critical signaling pathways. Plasmalogens have been implicated in antioxidative defense, membrane fusion, and cell signaling cascades—all vital for neural progenitor viability and differentiation. The newfound involvement of PEDS1 extends the functional repertoire of lipid metabolism in neurodevelopment, suggesting that metabolic dysregulation may be an underappreciated driver of neurological disease.

This work also sheds light on the broader spectrum of molecular pathways essential for neurodevelopment. By categorizing genes according to their functional annotations, the study highlights distinct clusters of gene functions—transcriptional regulation, metabolic processing, cytoskeletal organization, and vesicular trafficking—that coalesce in coordinated networks to guide neuronal differentiation. Many of these networks remain unexplored in the context of human diseases, presenting a fertile ground for future research.

This integrative approach—merging CRISPR functional genomics, mouse genetics, and human patient data—sets a new benchmark for discovery in neurodevelopmental biology. Notably, the identification of PEDS1 as a disease gene emphasizes the necessity of investigating metabolic enzymes and lipid biosynthesis pathways, areas traditionally underrepresented in neurogenetic studies. Furthermore, the study’s demonstration that disruptions in these pathways lead to distinct anatomical and functional consequences opens new avenues for therapeutic targeting.

The implications of this study extend beyond academic curiosity; they hold promise for improving diagnostic frameworks and patient stratification in clinical genetics. Genetic screening panels for NDDs may soon incorporate these newly identified essential genes, including PEDS1, facilitating earlier diagnosis and potentially guiding interventions tailored to the specific molecular defect. Moreover, understanding the pathways underlying these defects paves the way for the development of novel therapies aimed at modulating cell cycle progression or lipid metabolism in affected individuals.

Considering the complexity of neurodevelopment, where numerous genes often converge on common cellular processes, the study’s findings reinforce the paradigm that both rare and common genetic variants contribute collectively to disease phenotypes. The broad spectrum of essential genes uncovered here also suggests that neurodevelopmental disorders may arise from diverse, yet interconnected mechanisms, reflecting the multifaceted nature of brain development.

Beyond neurogenetics, this research exemplifies the power of functional genomics combined with advanced animal models to illuminate gene function in vivo. The approach employed could be adapted to investigate other developmental processes and diseases, where delineating causative genes remains a critical scientific challenge. The methodology holds particular promise for identifying disease-related genes not apparent through conventional genetic association studies alone.

Critically, while the study reveals numerous candidate genes, it also points to the remaining gaps—the fact that many essential genes have yet to be linked to specific human phenotypes underscores the complexity of translating mouse model findings to clinical practice. Future studies will need to assess the penetrance and expressivity of variants in these genes across diverse populations, along with their interactive effects with environmental factors.

In sum, this research marks a significant leap forward in decoding the genetic architecture of neurodevelopmental disorders. Through the comprehensive interrogation of gene function during neuronal differentiation and corroborative animal studies, the authors have revealed new players and pathways essential for normal brain development. The identification of PEDS1, in particular, heralds a new class of metabolic genes implicated in NDDs, expanding the horizon for diagnosis and therapy.

As neurogenetics continues to evolve, the integration of genome-wide functional approaches with developmental biology and clinical genomics will be pivotal. This study exemplifies the transformative impact of such integration and sets the stage for a new era of precision medicine in neurodevelopmental disorders. The collective insights gleaned here not only enhance our molecular understanding but also ignite hope for affected individuals and families seeking answers and treatments in the face of neurodevelopmental challenges.

Subject of Research: Neurodevelopmental disorders; genetic pathways essential for neuronal differentiation; functional genomics using CRISPR knockout screens in mouse embryonic stem cells; role of PEDS1 in neurodevelopment.

Article Title: CRISPR knockout screens reveal genes and pathways essential for neuronal differentiation and implicate PEDS1 in neurodevelopment.

Article References:
Amelan, A., Collins, S.C., Damseh, N.S. et al. CRISPR knockout screens reveal genes and pathways essential for neuronal differentiation and implicate PEDS1 in neurodevelopment. Nat Neurosci (2026). https://doi.org/10.1038/s41593-025-02165-0

Image Credits: AI Generated

DOI: https://doi.org/10.1038/s41593-025-02165-0