Frontiers in Neuroscience

BackgroundMotor threshold (MT) estimation is fundamental to transcranial magnetic stimulation (TMS), guiding individualized stimulation intensity in research and therapy. Conventional methods such as the 5-out-of-10 rule require many stimuli, while adaptive approaches like Parameter Estimation by Sequential Testing (PEST) improve efficiency but can exhibit poor convergence under certain conditions. ObjectiveThis study introduces the Bayesian Uncertainty Dynamic Algorithm for Parameter Estimatio...

A critical challenge in endocrine neurosurgery is intraoperative discrimination between normal pituitary tissue and pituitary neuroendocrine tumors (PitNETs). Suggesting the universal persistence of near-infrared autofluorescence (NIRAF) in endocrine organs and inspired by routine clinical use of NIRAF for parathyroid gland identification, we discovered that pituitary NIRAF can be employed for label-free transsphenoidal surgery guidance. Ex vivo confocal spectral imaging of 33 specimens identifi...

In this randomized, double-blind, controlled trial of 8 weeks of repetitive transcranial magnetic stimulation (rTMS) for chronic pain, we compared the classic primary motor cortex (M1) rTMS with a novel target-selection strategy based on pre-therapy cortical connectivity. Guided by principles of homeostatic plasticity, we tested whether stimulating the cortical site with the lowest pre-therapy global connectivity would be more effective than two active comparators: stimulating the site with the ...

Multiple sclerosis (MS) is a chronic neurodegenerative disease characterised by progressive neurological disability and heterogeneous symptom trajectories. Current clinical monitoring methods, including magnetic resonance imaging (MRI) and episodic neurological assessments, provide limited insight into subtle disease progression and functional changes. Digital health technologies integrating multimodal biosignals and behavioural assessments may enable continuous monitoring and personalised rehab...

Resting-state electroencephalography (EEG) has been proposed as a scalable source of biomarkers for chronic pain, but its clinical potential remains uncertain. To systematically evaluate this potential, we benchmarked nine modeling strategies, spanning conventional machine learning with handcrafted features to state-of-the-art deep learning. Across 72 configurations of signal representations and model architectures, we trained models to predict self-reported pain intensity, using chronological a...

Oscillatory coupling between respiration, heart rate, and cortical function is fundamental to physiological regulation yet remains poorly characterized in humans. Diminished respiratory heart rate variability (RespHRV)--the rhythmic heart rate modulation accompanying respiration--has emerged as a transdiagnostic biomarker of mental and physical health, reduced in anxiety, depression, cardiovascular disease, and aging (Beauchaine & Thayer, 2015; Menuet & Gourine et al., 2025). However, the cortic...

Actigraphy is a popular behavioral sleep assessment tool in research and clinical practice. Hierarchical hand-scoring approaches remain the standard for actigraphy rest interval estimation, but can be impractical for large cohort studies and suffer from reproducibility problems. We developed a semi-automated pipeline (actiSleep) to set rest intervals consistent with best-practice hand-scoring algorithms incorporating event marker, diary, light, and activity data. To evaluate actiSleep performanc...

Nocturnal glucose regulation is modulated by autonomic and circadian mechanisms, yet their dynamic interplay in apparently healthy, free-living populations remains poorly studied. Here, we assessed 227,860 nights of concurrent sleep data from Ultrahuman AIR ring and M1 continuous glucose monitoring (CGM) system across 5849 adults globally to examine nocturnal cardio-metabolic coupling. We found that higher sleep consistency was inversely associated with glucose variability, and vice versa. Unsup...

Background and Purpose: Magnetic resonance imaging (MRI) for radiation therapy treatment planning is currently being used in many anatomical sites to better visualize soft tissue landmarks, a technique known as an MRI simulation. A core component of modern MRI simulation configurations are the use of external laser positioning systems (ELPS) to help set up the patient. Though necessary for accurate and reproducible patient setup, the ELPS, if left on during imaging, may interfere negatively with...

Protocadherin-12 (PCDH12), a cell-adhesion protein belonging to the non-clustered protocadherin family, plays a crucial role in the establishment and regulation of neuronal connections and communication. Bi-allelic loss-of-function (LoF) variants in the PCDH12 gene have been associated with several neurodevelopmental disorders (NDDs) such as diencephalic-mesencephalic junction dysplasia (DMJD) syndrome, cerebral palsy, and cerebellar ataxia, often accompanied by ocular abnormalities. However, ge...

IntroductionThe eligibility of anti-amyloid disease-modifying therapies (DMTs) and their integration into clinical practice in some institutions requires a specific range of Mini-Mental State Examination (MMSE) scores. Reliance on this pencil-and-paper psychometric instrument imposes operational burdens and risks perpetuating health disparities due to the tests known educational and cultural biases. This study evaluates the efficacy of the Digital Clock and Recall (DCR) - a rapid, FDA-listed dig...

BackgroundLarge middle cerebral artery (MCA) infarctions can result in life-threatening cerebral edema. Quantitative brain atrophy may improve risk stratification for severe edema. We examined whether quantitative brain atrophy is associated with severe midline shift after large ischemic stroke and whether incorporating atrophy improves prediction beyond established clinical and radiographic predictors. MethodsThis was a retrospective observational cohort study of patients with [≥][1/2] MCA ...

We describe the design of the first non-pharmacological prevention trials of Parkinsons Disease worldwide: the randomised controlled Slow-SPEED trials. The three trials examine the feasibility and preliminary efficacy of a gamified, remotely administered exercise intervention vs. active control program over 18-36 months in the Netherlands (n=110), United Kingdom (n=110) and United States (n=600). Each trial focuses on a complementary prodromal subgroup: isolated/idiopathic REM sleep behavioural...

Background and objectives STXBP1-related disorder (STXBP1-RD), caused by pathogenic variants in the STXBP1 gene, is a rare neurodevelopmental condition, characterized by early-onset seizures, developmental delay, intellectual disability (ID), and prominent motor dysfunction. Despite the high prevalence of motor symptoms, systematic gait characterization remains limited. We therefore aimed to quantitively assess gait in individuals with STXBP1-RD. Methods In this cross-sectional study, we include...

ObjectiveTo compare early cerebrospinal fluid (CSF) cytokine profiles in intracerebral hemorrhage (ICH) versus subarachnoid hemorrhage (SAH), with a focus on angiography-negative SAH (anSAH). MethodsWe conducted a retrospective observational cohort study of adults with spontaneous hemorrhagic stroke (ICH or SAH). For cytokine analyses, we included patients with external ventricular drains (EVDs) and analyzed the first CSF sample obtained within 72 hours of symptom onset. Cytokines were measured...

PurposeTo investigate the effects of morning and evening narrowband blue light exposure on axial length, and to examine the short-term effect of morning blue light combined with myopic defocus on axial length. MethodsFor objective 1, 18 individuals underwent 60 minutes of narrowband blue light exposure (460nm) in the morning (9:00-11:00AM) and evening (5:00-7:00PM) of the same day. The axial length values were normalized to the average of the morning and evening axial length values. For objecti...

Background: Platform trials are an efficient trial design which enable testing of multiple interventions simultaneously. They could advance knowledge of treatments for intracerebral haemorrhage (ICH). We aimed to investigate the views of clinicians involved in stroke research on recruitment to a future platform trial for ICH. Methods: Between April and July 2025, we conducted a UK-wide online survey of clinicians actively involved in stroke research using convenience sampling through professiona...

Importance: Dementia is common in Parkinson's disease (PD), causing greater disability than other symptoms, but varies in timing. Although visual deficits are linked with PD dementia, how these interact with genetic factors to predict PD dementia has not been characterised. Objective: To investigate whether visual deficits and genetic factors predict PD dementia. Design: Large prospective longitudinal case-control study, mean follow-up 32.7 (SD=12.3) months. Setting: Cases were recruited between...

Health behaviors such as physical activity and sleep affect mental health, but the effect of each health behavior varies substantially across individuals, limiting the usefulness of generic behavioral recommendations. We collected one year of continuous wearable and ecological momentary assessment data from 3,139 participants in the Intern Health Study (2018-2023), and examined individual-level associations between wearable-derived features and mood across the internship year. The behaviors asso...

Background Whole-genome sequencing (WGS) has improved the diagnosis of rare genetic disorders, yet interpretation of non-coding variants that affect splicing remains challenging. In silico predictions alone are insufficient, and short-read RNA sequencing may fail to capture complex or low-abundance splicing events. Targeted amplicon-based long-read RNA sequencing (Amp-LRS) offers a cost-effective approach for functional validation of candidate splice-altering variants. Methods We applied Amp-LRS...