A groundbreaking study from researchers at the University of Tokyo has revealed a promising new avenue for alleviating certain autistic traits through a noninvasive brain stimulation technique known as brain state-driven neural stimulation (BDNS). Distinguished by its ability to monitor and influence the brain’s dynamic states in real time, BDNS represents a significant advance in understanding and potentially treating autism spectrum disorder (ASD) at a neurobiological level. This innovative approach combines electroencephalography (EEG) with transcranial magnetic stimulation (TMS) to administer targeted neural stimulation only when the brain becomes "stuck" in specific states, thereby promoting neural flexibility and mitigating behavioral rigidity commonly observed in ASD.
Autism spectrum disorder is a neurodevelopmental condition characterized by challenges in social interaction, communication, and the presence of restrictive and repetitive behaviors. Over recent decades, the diagnosis of ASD has become more prevalent, attributed to both better detection methods and a growing recognition of the spectrum’s breadth. Despite extensive research, biological treatments that effectively address the core neural mechanisms behind ASD have remained elusive. This new research led by Professor Takamitsu Watanabe and his team aims to bridge this gap by targeting the dynamic properties of brain activity underlying autistic behaviors, offering a fresh perspective beyond symptom management.
Central to their hypothesis is the concept of neural rigidity, a phenomenon whereby the brain’s ability to transition fluidly between different states is compromised. In neurotypical individuals, spontaneous fluctuations in neural activity enable flexible cognitive processing and adaptability; however, individuals with ASD show a marked reduction in these transitions. This neural inflexibility is proposed as a potential root cause for the coexistence of social difficulties, cognitive rigidity, and altered perceptual experiences typical of autism. The researchers’ work illustrates that neural rigidity is not merely correlated with ASD traits but could be causative, thus providing a unified neurobiological explanation for the condition’s diverse manifestations.
The investigation involved over forty adult volunteers diagnosed with level 1 ASD, indicative of mild symptom severity. Over six months, the participants underwent a series of assessments combining brain imaging techniques and behavioral evaluations. A significant portion of the study focused on assessing baseline brain dynamics through functional MRI and EEG, establishing individual profiles of neural rigidity related to both social and nonsocial traits. Following computational modeling, the team applied BDNS, a technique designed to disrupt the brain’s stuck states by delivering carefully timed pulses of TMS.
BDNS’s novelty lies in its feedback-controlled design, which differentiates it from typical brain stimulation approaches that deliver signals non-selectively. By continuously monitoring brain activity, the system identifies moments when the brain is trapped in a rigid state and triggers a brief magnetic pulse to nudge it toward a more flexible state. This precision reduces unnecessary stimulation and enhances therapeutic specificity. The painless and noninvasive nature of the method makes it particularly attractive for clinical use, potentially overcoming the barriers associated with invasive interventions or pharmacological treatments with systemic side effects.
The results observed in the study were both encouraging and somewhat unexpected in their temporal dynamics. Behavioral improvements associated with cognitive flexibility emerged rapidly, sometimes within the first week of BDNS treatment. However, changes related to social interaction and perceptual processing developed more gradually, requiring six to seven weeks before exhibiting statistically significant improvements. These findings suggest a hierarchical or phased neuroplastic response, where different neural circuits and behavioral domains respond at varying rates to the same stimulation paradigm.
Despite the promising outcomes, the authors caution that the effects of BDNS appeared to diminish roughly two months after the cessation of treatment, highlighting the need for refining stimulation protocols to achieve sustained benefits. Future investigations will need to optimize treatment duration, frequency, and intensity while expanding participant demographics to include a broader age range and individuals exhibiting varying ASD severity. This next phase of research is critical to establish BDNS as a robust clinical modality and understand the mechanisms underlying the persistence or decay of its effects.
Beyond ASD, the versatility of BDNS opens the possibility for its application to other neuropsychiatric disorders characterized by abnormal brain-state dynamics. The research team is exploring its potential in conditions such as attention deficit hyperactivity disorder (ADHD) and obsessive-compulsive disorder (OCD), which involve either excessive or deficient neural flexibility. Early insights suggest that similarly tailored brain-state monitoring and stimulation may rebalance neural dynamics in these disorders, thus broadening the impact of this technology.
Methodologically, the integration of EEG monitoring with TMS is a pivotal advance, allowing for closed-loop stimulation. Closed-loop systems offer a level of precision unattainable by open-loop approaches, as they adapt treatment in real time according to an individual’s fluctuating neural landscape. This paradigm shift could represent the frontier for neuromodulation therapies, moving away from one-size-fits-all protocols toward individualized interventions grounded in neurophysiological biomarkers.
The implications of successfully reducing neural rigidity extend beyond immediate behavioral improvements. Enhancing neural flexibility may also increase an individual’s capacity for learning, adaptation, and engagement with their environment, potentially leading to broader quality-of-life benefits. Moreover, mechanistic understanding gained through this research could inspire new pharmacological agents or combined therapeutic strategies that synergize with BDNS to optimize neurological function.
In summary, this pioneering research underscores the value of targeting dynamic brain states rather than static regional abnormalities in neurodevelopmental disorders. The evidence positions neural rigidity as a central biological mechanism in autism and highlights BDNS as a revolutionary approach to mitigating its behavioral impacts. While further studies are necessary to translate these findings into widely accessible treatments, this work marks a seminal step toward reshaping the therapeutic landscape for ASD and related conditions.
As neurotechnology continues to evolve, interventions like BDNS epitomize the promise of merging neuroscience with engineering to create subtle, effective, and patient-tailored treatments. With continued support and investigation, such approaches could fundamentally alter how we understand and manage complex brain disorders, ultimately fostering greater neurodiversity and inclusion within society.
Subject of Research: People
Article Title: Non-invasive reduction of neural rigidity alters autistic behaviours in humans
News Publication Date: 6-Jun-2025
Web References: http://dx.doi.org/10.1038/s41593-025-01961-y
Image Credits: ©2025 T. Watanabe and H. Yamasue CC-BY-ND
Keywords: Autism Spectrum Disorder, Neural Rigidity, Brain State Dynamics, Transcranial Magnetic Stimulation, Electroencephalography, Brain State-Driven Neural Stimulation, Neuroplasticity, Noninvasive Therapy, Neurodevelopmental Disorders, Cognitive Flexibility, Closed-Loop Neuromodulation
