In a groundbreaking study poised to reshape our understanding of neurodevelopmental disorders, researchers have uncovered critical brain markers that connect the delicate balance of neural excitation and inhibition with sensory processing from infancy. The findings, emerging from highly detailed longitudinal studies predominantly featuring children at elevated risk for autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD), offer promising avenues for early identification and intervention strategies.
This ambitious investigation, spearheaded by Carter Leno, V., Begum-Ali, J., Goodwin, A., and colleagues, meticulously tracked cortical activity in infants over time, unraveling the intricate relationship between excitation/inhibition (E/I) balance and how early sensory experiences shape neurodevelopmental trajectories. Published in the esteemed journal Translational Psychiatry in 2025, this research delves deep into the neurophysiological frameworks that might underlie the sensory responsivity abnormalities observed in ASD and ADHD.
The human brain relies on a fine-tuned equilibrium between excitatory and inhibitory neurotransmission to process sensory inputs effectively. Excitatory signals, primarily mediated by glutamatergic neurons, promote neural firing, while inhibitory processes, mostly governed by GABAergic neurons, regulate and dampen this activity. Disruptions in this balance often manifest as atypical sensory sensitivities, ranging from hyperreactivity to hypo-responsiveness, both hallmark features of autism and attention deficits. The study offers compelling evidence that these E/I imbalances are not just concurrent phenomena but can be detected very early in life, potentially setting the stage for later neurodevelopmental challenges.
By applying advanced neuroimaging techniques and electrophysiological assessments to infant cohorts enriched for ASD and ADHD risk, the team identified distinct cortical markers indicative of E/I dysregulation. These biomarkers were robustly correlated with sensory responsivity measures, charting a developmental trajectory that illuminates how early brain function predisposes to the behavioral phenotypes seen later in childhood. This represents a significant advancement beyond previous cross-sectional snapshots, moving the field toward dynamic, mechanistically grounded models of neurodevelopment.
Intricate patterns emerged demonstrating that infants who went on to develop heightened sensory responsiveness or atypical attention had specific neural signatures detectable well before clinical symptoms appeared. These neural signatures characterized altered oscillatory activity and disrupted synaptic modulation within sensory-related cortical regions. This nuanced insight bolsters the hypothesis that sensory processing atypicalities emerge from fundamental neurobiological alterations rather than merely reflecting downstream behavioral adaptations.
The research team also explored how these cortical markers related longitudinally to both sensory behavior and broader clinical outcomes. This connection underscores how early neural excitatory/inhibitory deficits potentially cascade into complex neurocognitive profiles seen in ASD and ADHD. Importantly, the findings highlight the potential for developing non-invasive neurophysiological measures to serve as early biomarkers, enabling clinicians to identify at-risk infants during critical windows for intervention.
Technological innovations were central to this breakthrough. The utilization of high-density electroencephalography (EEG) in a longitudinal framework provided unprecedented temporal and spatial resolution, capturing the dynamic shifts in cortical excitability that may represent the earliest neural footprints of autism and ADHD. Such methodological rigor allows researchers to parse apart the nuances of neurochemical imbalance, distinguishing between excitation-driven hyperactivity and inhibition-related suppression mechanisms with remarkable precision.
Critical too was the study’s emphasis on sensory responsivity—a domain historically underappreciated in neurodevelopmental diagnostics. Traditionally overshadowed by core social and attention symptoms, sensory processing abnormalities are now recognized as fundamental to the lived experience of individuals with ASD and ADHD. This research firmly integrates sensory markers with underlying neural mechanisms, advocating for sensory processing to be considered a central target for therapeutic strategies.
Moreover, the study provides a richer understanding of how genetic and environmental factors may converge on the E/I balance, influencing early brain circuit maturation. Longitudinal data allowed the research team to monitor how different levels of sensory exposure and caregiver interaction modulated cortical excitatory and inhibitory functions, emphasizing a complex interplay between biology and experience.
With the unveiling of these cortical excitation/inhibition markers, the future of pediatric neurodevelopmental assessment appears poised for transformation. By shifting focus to the earliest brain-based signatures, clinicians may move beyond symptom-based diagnoses toward predictive frameworks grounded in neurophysiology. This could revolutionize timing and tailoring of interventions, potentially alleviating or even preventing the exacerbation of sensory-related dysfunction.
The findings also provoke further questions about the plasticity of the E/I balance during infancy. Could targeted sensory interventions recalibrate E/I equilibrium, normalizing neural circuitry before maladaptive patterns consolidate? Such translational implications foster a hopeful direction for autism and ADHD treatment research, emphasizing early brain health as a pivotal factor.
Internationally, the study resonates with ongoing efforts to define objective biomarkers for neurodevelopmental disorders—fields that have historically grappled with subjective assessments and diagnostic heterogeneity. This work’s contribution strengthens the neurobiological scaffolding, offering a clear, measurable index of neural function that correlates with sensory processing traits from infancy onwards.
Neuroscientists and clinicians alike are likely to find these revelations impactful, prompting renewed focus on early-life cortical dynamics. By bridging gaps between fundamental neuroscience, developmental psychology, and clinical practice, the study charts a course toward integrated models of neurodevelopmental disorder etiology.
Furthermore, this research invites expanded studies across diverse populations and with varied environmental contexts to validate and extend these findings. Understanding how universal or context-specific these E/I cortical markers are will refine their utility in precision medicine approaches, tailoring care to individual neurodevelopmental profiles.
In summary, this seminal work not only advances science’s grasp of early brain mechanisms linked to ASD and ADHD but also lays an essential foundation for innovating early screening and intervention strategies. Through unveiling how cortical excitation/inhibition balance governs sensory responsivity during infancy, it opens a new frontier in understanding and ultimately mitigating some of the most challenging aspects of these complex disorders.
As neuroscience continues to unravel the enigmatic interplay of excitation and inhibition shaping the developing brain, the potential to transform lives through timely, mechanism-driven interventions grows ever brighter. The research by Carter Leno and colleagues exemplifies this promise, heralding a pivotal leap toward deciphering the roots of neurodevelopmental diversity.
Subject of Research:
Non-invasive cortical markers of excitation/inhibition balance and their association with sensory responsivity in infants, with implications for autism spectrum disorder and attention deficit hyperactivity disorder.
Article Title:
Cortical markers of excitation/inhibition balance are associated with sensory responsivity from infancy in longitudinal cohorts enriched for autism and ADHD.
Article References:
Carter Leno, V., Begum-Ali, J., Goodwin, A. et al. (2025). Cortical markers of excitation/inhibition balance are associated with sensory responsivity from infancy in longitudinal cohorts enriched for autism and ADHD. Transl Psychiatry. https://doi.org/10.1038/s41398-025-03791-9
Image Credits: AI Generated
