This innovative technique, rTMS, delivers targeted magnetic pulses noninvasively to circuits deep within the brain, effectively altering neuronal activity. While traditional cessation methods, including pharmacological aids and behavioral therapies, have achieved limited long-term success, this approach considers the biological substrate of addiction—a dynamic imbalance between craving-driven and control-related brain systems. The study, recently published in the Journal of Psychiatric Research, explored how stimulating discrete regions associated with decision-making and reward processing can influence smoking behavior.

The core hypothesis rests on two key brain regions. First is the dorsolateral prefrontal cortex (DLPFC), a prefrontal area heavily involved in executive functions such as impulse control, decision-making, and moderating inappropriate behaviors. The other focal point is the medial orbitofrontal cortex (mOFC), central to processing rewards and craving sensations. By leveraging rTMS to either reinforce the DLPFC or suppress the mOFC, researchers aimed to understand which neural manipulation more effectively diminishes cigarette consumption.

In a rigorously designed clinical trial, adult smokers actively seeking to quit were randomized into three groups: one received high-frequency rTMS targeting the DLPFC with the goal of augmenting self-regulatory control; a second group underwent rTMS aimed at downregulating activity in the mOFC to directly tamp down craving signals; and a control group was given a sham treatment to serve as a placebo baseline. Sessions were administered over a three-week period, with each participant receiving 15 rTMS treatments. Functional brain imaging ensured stimulation precision, embodying a true precision medicine paradigm personalized to individual neuroanatomy.

The results were compelling. Participants who underwent DLPFC-focused stimulation demonstrated a profound reduction in cigarette consumption, quitting on average more than 11 cigarettes daily – a statistically and clinically significant outcome when compared to both sham and mOFC-targeted groups. Moreover, these subjects reported lower craving intensity and exhibited decreased carbon monoxide biomarkers, objectively verifying their reduced intake. Perhaps most excitingly, these benefits persisted at least one month post-intervention, suggesting durable neuroplastic changes within executive control circuitry that outlasted the active treatment phase.

Neuroimaging elucidated the underlying mechanisms of this success. Enhanced activity in the prefrontal cortex was accompanied by suppressed engagement of reward-related brain areas including the orbitofrontal cortex, highlighting a top-down modulatory effect where re-energizing control networks yields a secondary dampening of craving signals. Notably, the extent of these neural shifts directly correlated with the degree of reduction in smoking behavior, reinforcing the causal implication of brain circuit modulation in achieving cessation.

Conversely, efforts to reduce cigarette use via direct inhibition of the mOFC, aimed at suppressing craving, did not yield comparable behavioral or biological improvements. This finding underscores a vital insight: addiction is not solely a function of excessive craving activation but also a failure in the brain’s capacity to exert inhibitory control. Enhancing self-regulatory mechanisms surpasses attempts to blunt craving in reversing smoking habits.

The implications of this research are far-reaching, particularly for populations where traditional cessation interventions have failed. Many smokers experience intolerable side effects with pharmacotherapies or relapse despite repeated quit attempts. For cancer patients and others facing acute health risks exacerbated by smoking, novel tools that intervene at the neural circuit level hold transformational potential. The Hollings Cancer Center’s existing Tobacco Treatment Program, which integrates counseling and medication, could be complemented by rTMS to target addiction’s neurological roots more precisely and effectively.

This study signals a new era where personalized neuromodulation becomes an integral part of addiction medicine. Harnessing the brain’s plasticity, it redefines cessation as an achievable neurological realignment rather than mere behavioral modification. Although constrained by a modest sample size, these findings justify larger-scale clinical trials now underway to confirm therapeutic efficacy and optimal treatment regimens tailored to individual neural profiles.

Ultimately, the strategy emerging from this research champions restoring balance within the brain’s competing systems. Rather than suppressing cravings directly, empowering the brain’s natural control systems to override the lure of nicotine establishes a more sustainable path to quitting. It is a shift from defensive to proactive intervention—the brain is taught to say no.

In an age when smoking remains a leading preventable cause of death worldwide, these advancements breathe fresh hope into the cessation landscape. Repetitive transcranial magnetic stimulation targeting the dorsolateral prefrontal cortex may soon join the arsenal of evidence-based strategies that help millions break free from the grip of nicotine dependence, offering a science-driven, neurocentric approach that aligns with the modern understanding of addiction as a brain disease.

Subject of Research: People
Article Title: DLPFC rTMS is more effective than sham or orbitofrontal stimulation for smoking cessation and alters frontal brain activity: A double-blind, sham-controlled randomized clinical trial
News Publication Date: 4-Mar-2026
Web References: http://dx.doi.org/10.1016/j.jpsychires.2026.02.053
Image Credits: Medical University of South Carolina
Keywords: Brain stimulation, Transcranial magnetic stimulation, Brain, Dorsolateral prefrontal cortex

Focused ultrasound has intrigued neuroscientists and engineers alike for over a decade due to its ability to target brain regions with remarkable spatial precision. Unlike traditional electrical stimulation methods, ultrasound waves can penetrate deep brain structures noninvasively. Nonetheless, the detailed effects of these waves on human cortical activity remained elusive, largely because prior studies encountered two significant obstacles. First, the ultrasound device emits a faint beeping noise that inadvertently activates auditory pathways, confounding results. Second, functional MRI scans used in earlier experiments often generated misleading signals that complicated interpretations about direct neural activation.

To circumvent these limitations, the research group employed concurrent whole-brain electroencephalography (EEG) during resting-state conditions in 27 human participants. This approach allowed real-time monitoring of brainwave patterns with millisecond-level temporal resolution. They systematically compared three stimulation paradigms: low-intensity transcranial focused ultrasound (tFUS) alone, a mild form of electrical brain stimulation called transcranial direct current stimulation (tDCS), and an innovative hybrid technique that integrates both modalities, termed transcranial electro-acoustic stimulation (tEAS). Their rigorous experimental design was crucial to disentangle the distinct contributions of ultrasound and electrical inputs.

Intriguingly, the results demonstrated that neither tFUS nor tDCS in isolation generated robust or localized brain responses in the targeted cortical areas. However, the simultaneous application of these two forms of stimulation induced significant and highly specific cortical activation. This synergistic effect provides compelling evidence that focused ultrasound alone subtly primes neuronal excitability without directly causing firing, but when paired with electrical stimulation, the combined inputs surpass the activation threshold of neurons.

Professor Bin He, lead author and renowned biomedical engineering expert at Carnegie Mellon University, highlighted the importance of this discovery: “By combining ultrasound with electrical stimulation, we could for the first time clearly observe the influence of focused ultrasound on human cortical activity. This dual-stimulation strategy helps clarify why earlier studies reported conflicting outcomes, as ultrasound’s effects are more modulatory than stimulatory.”

The research team bolstered their empirical findings with a companion computational model, which elucidates the neural mechanisms underlying their observations. According to the model, ultrasound weakly modulates neuronal membrane potentials, effectively “priming” the neurons. Concurrent mild electrical currents then push these primed neurons beyond their activation threshold, triggering full action potentials. This additive effect explains the necessity of combining modalities to attain pronounced cortical responses and accounts for the inconsistencies in previous ultrasound-only studies.

This novel understanding redefines the role of focused ultrasound from a direct stimulator to a gentle modulator of brain excitability. The newly developed transcranial electro-acoustic stimulation technique leverages the spatial precision of ultrasound while harnessing the enhanced efficacy of concurrent electrical stimulation, opening new avenues for targeted neuromodulation therapies.

The implications of this research extend far beyond basic neuroscience. The noninvasive nature and safety profile of tEAS make it an attractive candidate for clinical applications, particularly for neurological disorders that require precise and controlled interventions. Conditions such as chronic pain syndromes and epilepsy, which have shown responsiveness to various brain stimulation techniques, could benefit significantly from this refined approach.

Looking ahead, Professor He and his collaborators plan to integrate transcranial focused ultrasound with advanced brain-computer interface (BCI) technologies. This integration seeks to enhance human-machine interaction by providing precise and controllable neural modulation, thereby improving the responsiveness and adaptability of BCIs. The team also aims to explore the therapeutic utility of tEAS in clinical populations, tailoring interventions that maximize specificity and minimize side effects.

Another striking aspect of this work is the methodological innovation that eliminates auditory confounds inherent in ultrasound stimulation. By carefully isolating the brain’s electrical responses via EEG, the study sets a new standard for future investigations in the field. This refined experimental framework enables researchers to disentangle genuine neural effects from sensory artefacts, ensuring more reliable and reproducible outcomes.

The multidisciplinary approach, combining engineering, computational modeling, and human neurophysiology, underscores the importance of collaborative efforts in advancing brain science. The convergence of these fields has created a powerful platform for addressing long-standing challenges in noninvasive brain stimulation and unlocking new therapeutic possibilities.

As tEAS technology evolves, it promises to enrich our understanding of brain function and plasticity, facilitating interventions that are both gentle and precise. This bears profound implications not only for treating neurological diseases but also for enhancing cognitive performance and mental well-being in healthy individuals.

In conclusion, Carnegie Mellon University’s breakthrough research represents a significant leap forward in noninvasive neuromodulation. By demonstrating the synergistic effects of concurrent transcranial focused ultrasound and electrical stimulation, the team has charted a new course for brain stimulation science, transforming ultrasound from a controversial tool into a sophisticated means of targeted cortical activation. This advance opens the door to a wide spectrum of clinical and technological applications that could redefine neurological healthcare in the years to come.

Subject of Research: Noninvasive brain stimulation using transcranial focused ultrasound combined with electrical stimulation to induce targeted cortical activation.

Article Title: Transcranial focused ultrasound induces source localizable cortical activation in resting state humans when applied concurrently with transcranial electric stimulation

News Publication Date: 10-Mar-2026

Web References: DOI: 10.1038/s41467-026-69853-8

Keywords

Neuroscience, focused ultrasound, transcranial stimulation, EEG, brain modulation, neuromodulation, brain-computer interface, neuroengineering, epilepsy, chronic pain, noninvasive brain stimulation, computational modeling

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

Prenatal alcohol exposure constitutes a significant public health concern, impacting approximately 5% of children in the United States. These children frequently exhibit a constellation of ADHD-like symptoms including hyperactivity, impulsivity, and marked deficits in executive function domains such as sustained attention, working memory, and behavioral organization. Conventional pharmacological interventions, such as psychostimulant medications like methylphenidate, tend to have limited efficacy in this subset of patients and, in some cases, may exacerbate symptom severity or lead to intolerable side effects.

The clinical trial, spearheaded by Dr. Joseph O’Neill, an adjunct professor of child psychiatry at UCLA, aims to explore whether nightly application of TNS—a noninvasive brain stimulation technique—can serve as a feasible and effective home-based therapy. The TNS modality functions through electrode patches positioned on the forehead, which deliver gentle electrical impulses targeting the trigeminal nerve during sleep. Activation of this cranial nerve has been shown in prior studies to engage cortical and subcortical regions implicated in attentional control and cognitive regulation.

The U.S. Food and Drug Administration (FDA) preliminarily approved the use of external TNS devices for children aged seven to twelve diagnosed with ADHD in 2019, following clinical evidence demonstrating safety and symptomatic improvement. Nonetheless, the therapeutic potential of TNS in children with prenatal alcohol exposure remains uncharted territory, underscoring the novelty and significance of this investigative effort.

The upcoming two-year pilot trial will enroll 30 children between the ages of eight and twelve who have documented prenatal alcohol exposure and exhibit ADHD-related impairments. Participants’ families will receive the Monarch eTNS device from NeuroSigma, Inc., a Los Angeles-based biotechnology company specializing in neurostimulation technologies. Parents will be instructed to apply the device nightly for a consecutive four-week period, enabling continuous stimulation throughout their child’s sleep cycle.

A critical aspect of the research protocol involves comprehensive monitoring of executive function changes, sleep quality, and any negative or adverse effects potentially arising from the therapy. Both subjective assessments—including parental and child tolerability evaluations—and objective behavioral measures will contribute to a multidimensional appraisal of treatment outcomes and adherence feasibility within a naturalistic, at-home setting.

Should the pilot data reveal promising results regarding safety, tolerability, and preliminary efficacy, the research team plans to advance to a randomized crossover trial, expanding the participant pool and duration. This subsequent phase aims to rigorously validate the therapeutic benefits of TNS while controlling for placebo effects. The National Institute on Alcohol Abuse and Alcoholism (NIAAA) is committed to supporting this expansion with grant funding reaching up to $2.1 million over three years.

From a neurological perspective, trigeminal nerve stimulation capitalizes on an accessible peripheral nerve that transmits sensory information to brainstem nuclei interconnected with key attentional networks. By applying calibrated electrical pulses, TNS may facilitate neuroplastic changes and improve dysregulated neural circuits implicated in ADHD pathophysiology, particularly in children whose neurodevelopment has been compromised by fetal alcohol exposure.

While pharmacotherapy remains the mainstay in ADHD management, the search for alternative, non-pharmacological interventions is urgent, especially for children who experience adverse reactions or inadequate response to medications. The prospect of a safe, user-friendly, and non-addictive intervention that can be administered during sleep holds transformative potential for clinical practice and quality of life for affected families.

Dr. Mary O’Connor, professor emerita at the UCLA David Geffen School of Medicine and co-lead on the study, expressed enthusiasm about the potential impact this research could yield. She emphasized the urgent need for innovative treatments tailored to the unique neurocognitive profiles of children affected by prenatal alcohol exposure, who frequently face lifelong challenges and societal stigma.

The trial is currently recruiting participants, and families interested in enrollment are encouraged to reach out via direct email, phone contact, or through the study’s online screening platform. This recruitment effort underscores the collaborative engagement between researchers, clinicians, and families, all united by a common goal to enhance therapeutic options and ultimately foster better developmental trajectories.

In a broader context, this research exemplifies the fusion of neuroscience, medical device innovation, and child psychiatry, epitomizing how targeted neurostimulation can revolutionize the management of complex neurodevelopmental disorders. Should the MONARCH eTNS device prove successful, it may herald a new era where sleep-based neurotherapies complement or even substitute pharmacological treatments, offering personalized and accessible care.

As the scientific community closely follows this trailblazing study, the hope is that it will catalyze further investigation into the mechanisms underpinning ADHD and related cognitive impairments. Ultimately, the knowledge gained may inform the development of more refined neuromodulation strategies, paving the way for improved neurodevelopmental outcomes in vulnerable pediatric populations worldwide.

Subject of Research: People
Article Title: Not provided
News Publication Date: Not provided
Web References:

• FDA Clearance of TNS Device: https://www.fda.gov/news-events/press-announcements/fda-permits-marketing-first-medical-device-treatment-adhd
  References: Not provided
  Image Credits: Not provided

Keywords:
Attention deficit hyperactivity disorder, Children, Clinical trials, Sleep, Developmental disabilities, Cognitive control, Mental health, Wearable devices, Attention, Psychiatry, Electrodes, Scientific approaches, Clinical research, Research on children