Transcutaneous auricular vagus nerve stimulation: mechanisms, applications, and research progress

This review systematically examines the mechanisms of action, optimization of stimulation parameters and targets, and the research progress in the application of taVNS for neurological disorders and systemic conditions. Rather than merely cataloging existing findings, this review critically synthesizes recent advances with a focused emphasis on two core aspects: (1) the mechanistic convergence and divergence among neuroimaging, autonomic, and molecular pathways underlying taVNS effects; and (2) the methodological challenges and biomarker-driven strategies for optimizing stimulation parameters and personalizing treatment. By prioritizing these key directions over exhaustive enumeration of clinical applications, this review aims to provide a conceptually structured framework that distinguishes genuine progress from descriptive accumulation. Moreover, compared with previously published reviews on similar topics, the present work offers a distinctive contribution by integrating multi-modal mechanistic evidence into a testable model of taVNS action and critically evaluating the translational gap between parametric optimization in research settings and standardized clinical implementation. Furthermore, it provides an outlook on future research directions and technological developments, aiming to offer a comprehensive theoretical framework to inform both clinical translation and foundational research in this rapidly evolving field.

Contemporary pharmacological strategies for acute peripheral facial palsy: a narrative review with clinical decision considerations

Acute peripheral facial palsy (APFP) sometimes known as Bell’s palsy is a common neurological condition and is marked by the acute onset of lower motor weakness on one side of the face. Whereas spontaneous recovery is widespread, there is a significant rate of incomplete recovery, synkinesis, or enduring functional and psychosocial disability of patients. The past decades witnessed the improvement of the diagnostic and therapeutic plans, particularly the pharmacological and adjunctive ones, due to the developments in pathophysiological and clinical trials and the creation of guidelines. This narrative review summarizes the existing evidence on the classification, diagnosis, and treatment of APFP, particularly corticosteroid disease treatment, antiviral medication, combination therapy, adjunct, and rehabilitative therapies, and the future of precision medicine. Randomised controlled trials and high-quality systematic reviews have shown evidence in support of the early initiation of systemic corticosteroids within 72 h of symptom onset as the foundation of treatment practice, improving the likelihood of achieving full facial nerve recovery and less morbidity in the long run. Conversely, antiviral monotherapy has not demonstrated significant clinical benefit with combination therapy with antivirals potentially presenting some benefit to older patients and with severe cases of paralysis. New data highlight the significance of risk stratification, electrophysiological testing, and focal rehabilitation to maximize the results and reduce the sequelae. The developments in artificial intelligence, the work on biomarkers and adaptive clinical trial designs will likely enable more personalized prognostication and treatment choice. In general, a shift towards precision risk-based approaches to the management of acute peripheral facial palsy is also being considered and emerging diagnostic strategies, promotion of the use of corticosteroids as early as possible and focused adjunctive operations that are tailored to a child are becoming the key to improving functional outcomes in the long term.

Bridging the gap from mechanism to clinic: a translational perspective on taVNS for gastrointestinal disorders

In recent years, multiple clinical and translational studies have investigated the application and mechanisms of transcutaneous auricular vagus nerve stimulation (taVNS) in gastrointestinal disorders (GIDs), with consideration given to pathophysiology, stimulation parameters, and patient-specific factors. In this review, we systematically synthesize recent evidence from clinical trials and preclinical models published in leading gastroenterology and neurology journals. Our focus is on taVNS-mediated modulation of the brain–gut axis, particularly its role in improving autonomic balance, reducing visceral sensitivity, and attenuating inflammatory responses, with the aim of enhancing therapeutic outcomes in functional and inflammatory GIDs. There is a need to optimize stimulation protocols through mechanistic insights and to promote the use of this non-invasive, well-tolerated neuromodulation approach. These advances are essential for expanding taVNS accessibility in clinical practice, especially for patients with refractory symptoms, comorbid psychological conditions, and in settings where conventional treatments are limited or contraindicated. Personalized taVNS strategies and biomarker-guided dosing represent emerging trends in neuromodulation therapy. However, standardized protocols and predictive models have yet to be established for widespread clinical implementation.

EEG Biomarkers for ADHD Stimulant Treatment

Conditions: ADHD

Interventions: Drug: methylphenidate HCl; Drug: Mixed amphetamine salts extended release

Sponsors: Boston Children’s Hospital; Seattle Children’s Hospital; Tris Pharma, Inc.

Not yet recruiting

Without getting under your skin: non-invasive stimulation activates the vagus nerve

Cervical non-invasive vagus nerve stimulation (nVNS) has emerged as a practical neuromodulation approach with FDA-cleared indications in primary headache disorders, yet skepticism persists over whether transcutaneous stimulation can reliably engage vagal fibers or whether observed benefits reflect nonspecific cervical activation. Here, we synthesize converging anatomical, biophysical, physiological, and clinical evidence demonstrating that nVNS does, in fact, activate vagal pathways without surgical implantation. We first review cervical vagus anatomy and the biophysical basis for target engagement, including ultrasound-measured nerve depth and multi-scale computational models showing that clinically relevant stimulation can recruit predominantly large myelinated vagal fibers. We then integrate mechanistic evidence across complementary modalities: functional imaging consistently modulates canonical vagal projection sites (including brainstem nuclei), electrophysiology demonstrates peripheral vagal recruitment and centrally transmitted evoked responses, immune studies reveal reproducible suppression of pro-inflammatory cytokines consistent with cholinergic anti-inflammatory reflex engagement, and autonomic biomarkers show shifts toward increased parasympathetic tone. Finally, we contextualize these mechanistic findings with sham-controlled randomized trials in cluster headache and migraine, where nVNS repeatedly outperforms sham for acute and preventive outcomes with a favorable safety profile. Together, these independent lines of evidence form a coherent mechanistic fingerprint that is difficult to reconcile with placebo or superficial muscle stimulation accounts. We conclude that nVNS provides a credible, scalable means of accessing vagal neurophysiology and represents a clinically validated, paradigm-shifting advance in bioelectronic medicine.

Longitudinal changes in MMN and P3 during emotional processing in adolescents who engage in NSSI: a 12-week follow-up study

BackgroundAdolescents with nonsuicidal self-injury (NSSI) often show deficits in negative emotion regulation. Within the dual-process framework of implicit and explicit emotion regulation, these deficits may reflect an automatic bias toward negative information and insufficient later-stage controlled regulation. Whether routine clinical intervention modifies both early automatic detection and later controlled evaluation of negative emotional information remains unclear.MethodsIn a longitudinal sample of 32 adolescents with NSSI, we examined changes in mismatch negativity (MMN) and P3 components elicited during an emotional oddball task before and after a 12-week clinical intervention. At baseline and Week 12, participants completed clinical assessments and a two-choice visual emotional oddball task containing neutral standards and negative, positive, and neutral deviants while EEG was recorded. MMN (Fz, 240–300 ms) and P3 (Pz, 450–650 ms) amplitudes were derived from deviant-minus-standard difference waves, indexing pre-attentive deviance detection and controlled evaluation, respectively.ResultsThe intervention selectively modulated neurocognitive processing of negative deviants. Self-injury ideation days (p = .036) and NSSI episode frequency (p = .007) both significantly decreased. MMN absolute amplitude to negative stimuli decreased significantly (p = .047), suggesting attenuated automatic salience detection, whereas P3 amplitude to negative stimuli increased significantly (p = .027), indicating enhanced controlled evaluation. Responses to positive and neutral conditions and behavioural performance remained stable. No baseline ERP–clinical correlations emerged; post-intervention, NSSI ideation days correlated with positive P3 (r = 0.380, p = .032), and episode frequency with neutral P3 (r = 0.461, p = .008).ConclusionsA 12-week intervention may attenuate automatic negative bias while enhancing controlled evaluative processing in adolescents with NSSI, consistent with the implicit–explicit framework. MMN and P3 may serve as candidate biomarkers and temporally sensitive tools for tracking intervention response when behavioural performance is stable.
<![CDATA[Phase 2 depression trial shows ALTO-203 boosts attention, EEG theta-beta ratio and alertness, pointing to biomarker-guided dosing and precision psychiatry.]]>

AI Model Predicts Alzheimer’s Progression from a Single MRI Scan

Researchers at the University of California, San Francisco (UCSF) have developed an artificial intelligence model capable of predicting cognitive impairment and Alzheimer’s disease progression using only a single baseline MRI scan and basic demographic information. The approach, published in Nature Aging, could help make early Alzheimer’s assessment faster, more accessible, and less dependent on costly specialized testing.

Alzheimer’s diagnosis remains complex and resource-intensive

Alzheimer’s disease accounts for approximately 60% to 70% of dementia cases worldwide. Although structural brain changes and cognitive decline are hallmarks of the disease, accurately forecasting who will develop progressive impairment remains difficult.

Current diagnostic workflows often rely on multiple complementary techniques, including PET imaging, cerebrospinal fluid or blood biomarkers, genetic testing, and comprehensive neuropsychological assessments. While effective, these approaches can be expensive, time-consuming, and inaccessible in many healthcare settings.

MRI scans are among the most widely available clinical imaging tools for neurological assessment, but MRI data alone has historically struggled to capture the complexity and heterogeneity of Alzheimer’s disease progression when used in conventional AI frameworks.

To address this challenge, the UCSF team designed a multitask deep learning framework that combines domain-specific imaging knowledge with advanced machine learning methods to predict cognitive outcomes directly from structural MRI scans.

AI framework predicts cognition without invasive testing

Unlike many earlier Alzheimer’s prediction models, the new system does not require longitudinal imaging data, baseline cognitive testing, PET scans, or molecular biomarker analysis.

The researchers instead focused on extracting clinically meaningful information from a single baseline MRI scan. The framework was trained to perform several related tasks simultaneously, including tissue segmentation, Alzheimer’s diagnosis prediction, and estimation of both present and future cognitive performance.

A key innovation of the study was the development of a specialized image model that segments brain tissue into gray matter, white matter, and cerebrospinal fluid before generating cognitive predictions. According to the authors, this task-specific segmentation step allowed the model to learn biologically relevant spatial brain features more effectively than standard transfer-learning approaches.

Senior study author Ashish Raj, PhD, professor of radiology and biomedical imaging at UCSF, said the goal was to create a system that could be realistically implemented in routine clinical environments.

“Unlike previous approaches, our model does not require baseline cognitive assessment, specialized image pipelines, expensive PET scans, genetic analysis, or fluid proteomics, making it a fast, accurate, and easily implementable tool for most clinical settings,” Raj said in a statement.

Large imaging datasets improved robustness and generalizability

To train and validate the framework, the researchers used imaging and clinical data from the Alzheimer’s Disease Neuroimaging Initiative (ADNI), including MRI scans, demographic information, diagnoses, and cognitive assessments.

The team also incorporated MRI data from the Human Connectome Project Young Adult cohort, which contains scans from healthy younger adults with minimal age-related brain atrophy. According to the authors, exposing the model to healthy brain anatomy improved its ability to distinguish pathological neurodegeneration from normal aging.

An external validation cohort from the Dallas Lifespan Brain Study was additionally used to test the generalizability of the framework across independent datasets.

The researchers reported that the multitask framework outperformed existing AI methods, including standard transfer-learning approaches, in predicting clinically relevant outcomes. The model generated accurate predictions for Alzheimer’s diagnosis, tissue segmentation, current cognitive function, and future cognitive decline using only baseline MRI data.

The study also reported improvements in computational efficiency and processing speed compared with more complex MRI morphometry pipelines commonly used in neuroimaging research.

First author Daren Ma, MSc, a machine learning specialist in the Raj Lab at UCSF, said the framework could help clinicians identify at-risk patients earlier and streamline referrals for advanced neurological evaluation.

“We reported meaningful gains in speed and performance over other pipelines, which could prove valuable in developing a quick clinical prediction of cognitive impairment prior to referring the patient to a more advanced imaging lab and/or a full neuroradiology report,” Ma said.

Potential implications beyond Alzheimer’s disease

The researchers believe the framework could eventually be adapted for other neurodegenerative disorders characterized by structural brain changes and progressive cognitive decline.

Potential future applications include Parkinson’s disease, amyotrophic lateral sclerosis (ALS), and Huntington’s disease. The ability to estimate cognitive impairment using minimal baseline data may also prove useful in community healthcare settings where access to specialist neuropsychological testing is limited.

In addition, the model may have implications for clinical trial design. Identifying likely disease progressors early could help reduce trial size requirements and improve patient selection for studies evaluating disease-modifying therapies.

“The ability to correctly predict progressors from non-progressors using only baseline data can dramatically reduce sample sizes and cost,” Raj said.

The authors emphasized, however, that further validation will be necessary before the model can be broadly implemented in routine clinical practice. Future iterations of the framework may incorporate additional clinical measurements where available, including longitudinal MRI imaging, PET scans, genetics, and blood or cerebrospinal fluid biomarkers.

The study highlights the growing role of AI-driven imaging analysis in neurology and suggests that clinically accessible tools such as MRI may eventually support earlier and more scalable prediction of Alzheimer’s disease progression.

The post AI Model Predicts Alzheimer’s Progression from a Single MRI Scan appeared first on Inside Precision Medicine.

<![CDATA[Computational phenotyping reveals prodromal psychosis clues, connects biomarkers to symptoms, and shows why stress and cannabis reduction matters.]]>