Background/Objectives: Gut microbiota (GM) dysbiosis has been implicated in multiple sclerosis (MS) pathogenesis, influencing inflammation and neurodegeneration, but findings remain inconsistent due to environmental and methodological variability. This study aimed to identify possible microbial biomarkers of MS status and disease severity by profiling gut microbiota and short-chain fatty acid (SCFA) patterns in people with relapsing-remitting MS (pwRRMS), using household-matched healthy controls (HC) to minimize environmental variability. Methods: Twenty-four pwRRMS and their respective household-matched healthy controls (HC) were enrolled, with dietary and lifestyle habits monitored. GM composition was assessed by 16S rRNA gene sequencing, and fecal SCFAs were quantified using gas chromatography-mass spectrometry. PwRRMS were stratified by Expanded Disability Status Scale (EDSS) and Multiple Sclerosis Severity Score (MSSS). Results: β-diversity did not differ between groups. However, α-diversity was significantly reduced in pwRRMS, particularly in those with greater disability. Reduced diversity was associated with lower abundance of butyrate-producing genera (Roseburia, Faecalibacterium, Coprococcus) and enrichment of Oscillibacter and UBA1819, alongside a downward trend in fecal butyrate and propionate levels. Conclusions: RRMS and greater disease severity are associated with gut microbial alterations characterized by reduced SCFA-producing bacteria. Despite limitations including small sample size and sex imbalance, the household-matched design strengthens internal validity. Our findings highlight the potential of targeting the gut microbiota, an accessible compartment within the gut-brain axis, for MS management.

BACKGROUND AND AIMS:Obsessive-Compulsive Personality Disorder (OCPD) is marked by a pervasive preoccupation with orderliness, perfectionism, and control, often overlapping with Obsessive-Compulsive Disorder (OCD) in terms of rigid and repetitive behaviors. While OCD behaviors are ego-dystonic and confined to specific areas of life, OCPD behaviors are ego-syntonic and affect overall functioning. Although the relationship between OCD and OCPD has been object of investigation, the impact of OCPD comorbidity on OCD remains underexplored. This study examines potential clinical differences between OCD patients with and without comorbid OCPD, with a specific focus on duration of untreated illness (DUI). METHODS:A sample of 300 patients diagnosed with OCD was consecutively recruited from a OCD Tertiary Clinic. Patients with OCD were divided into two groups: those with OCD-only and those with comorbid OCPD. Sociodemographic and clinical variables were collected and compared between groups. An additional age- and sex-matched sensitivity analysis was performed to further assess the robustness of the main findings. RESULTS:Out of the 300 patients with OCD, 18.6% (n = 56) were also diagnosed with OCPD. The age at first pharmacological treatment was significantly higher in the OCD with OCPD group compared to the OCD-only group (32.16 ± 17.06 years vs. 27.48 ± 11.17 years; p < .05). The DUI was significantly longer in the OCD with OCPD group (9.2 ± 12.4 years vs. 6.10 ± 8.06 years; p < .05). These findings remained significant after controlling for potential confounding by age and sex through a 1:1 matched sensitivity analysis. CONCLUSION:Almost one out of five patients with OCD has comorbid OCPD. The ego-syntonic nature of OCPD beliefs may contribute to treatment delays, underscoring the importance of early identification of this specific comorbidity in OCD patients to improve treatment outcomes.

Sun exposure may influence MS susceptibility, but evidence in pediatric-onset MS (PedMS) is limited. We examined whether reduced early-childhood outdoor time (a proxy for lower sun exposure) is associated with PedMS risk. In the Italian multicenter PEDIGREE Study, environmental data were collected using the PEQ-IT questionnaire. We enrolled individuals < 18 years with PedMS and disease duration ≤ 5 years and controls without CNS inflammatory disorders. Outdoor time was reported by season and age (0–1, 1–2, 3–5 years); reduced activity was defined as < 60 min/week. We included 114 PedMS cases and 121 controls. Cases were 77.2

OBJECTIVE:Apathy is a common symptom across neurodegenerative diseases with origins still debated. "Vascular apathy hypothesis" by Van der Mast suggests vascular pathologies precede apathy. Other evidence points to dysfunction in dopamine pathways, driving apathy by impairing goal-directed behaviour. The impact of apathy on cognitive decline and autonomy, particularly with coexisting depression, remains unclear. This cross-sectional study aimed to (1) characterize apathy in vascular dementia, Parkinson's disease (PD), and Mild Cognitive Impairment-Alzheimer Disease (MCI-AD) regarding incidence, severity, and cognitive specificity; (2) differentiate effects of apathy and depression on cognitive impairment and daily autonomy (Activities of Daily Living [ADL]). METHOD:Fifty-three patients underwent neuropsychological testing and completed the Geriatric Depression Scale, Starkstein's Apathy Scale, and ADL questionnaire at a clinical neuropsychology outpatient setting in Milan. RESULTS:56% patients had cardiovascular pathologies, 20% had PD, and 22% had MCI-AD. Neither prevalence nor severity of apathy or depression differed significantly across diseases. Hierarchical regression showed apathy predicted language initiative controlling for depression (R2 = 0.249; F(2) = 4.144; p = .028), and inversely correlated with working memory, language and frontal functioning, while depression predicted autonomy controlling for apathy (R2 = 0.234; F (2) = 3.821; p = .036). CONCLUSIONS:Apathy is prevalent across different neurodegenerative diseases and exacerbates specific cognitive impairments. Distinguishing vascular apathy from other forms remains challenging.

Multiple sclerosis (MS) is a chronic inflammatory and neurodegenerative disease. Quantifying neuronal damage is a critical step for patient care. Neurofilament light chain (sNfL) and glial fibrillary acidic protein (sGFAP) are the most promising serum biomarkers reflecting neuronal damage and astroglial activation, respectively. This study analyzed sNfL and sGFAP in 177 MS patients and 71 healthy controls (HCs) using SIMOA technology, classifying patients as responders (Rs) or non-responders (NRs) based on "No Evidence of Disease Activity 3" (NEDA-3) status during two years of treatment. Longitudinal analyses were performed for Dimethyl fumarate (DMF) and Ocrelizumab (OCRE) treatment. Biomarker-age correlation analysis in HCs confirmed correlation between both NfL and GFAP, with age and cut-off values specific for age decades being calculated. Both biomarkers were higher in MS patients compared to HCs. sNfL showed a significant increase in NR patients overall. In contrast, sGFAP was elevated in the low-to-moderate-efficacy treatment agents (LETAs) NR group and also in the DMF NR subgroup, suggesting that it monitors persistent astrogliosis. Longitudinal analysis showed that both biomarkers decreased during DMF treatment after one year. During OCRE treatment, sNfL rapidly reduced to HC levels within one year, while sGFAP decreased only after two years. This highlights that OCRE acts differently on the pathological processes linked to the two biomarkers.

Peripheral facial nerve palsy (FNP) leads to motor impairment and psychosocial distress, often requiring prolonged rehabilitation. Emotional Training (ET) is a physiotherapy-based approach intrinsically compatible with technology-assisted and remote rehabilitation models. However, its clinical effects across different FNP etiologies and management pathways remain underexplored. To investigate the motorfunctional and psychological effects of ET in patients with peripheral FNP, comparing individuals who had iatrogenic, neoplastic or traumatic damage and underwent triple innervation surgery with patients affected by idiopathic FNP treated conservatively, while exploring implications for digitally supported rehabilitation. In this prospective, exploratory, observational pilot study, 14 patients with unilateral peripheral FNP were allocated into two cohorts based on etiology and prior clinical management, i.e., SURGICAL (n = 7; iatrogenic, neoplastic or traumatic FNP, triple innervation surgery) and NON-SURGICAL (n = 7; Bell’s palsy, conservative therapy). All participants underwent a standardized ET protocol over 20 weeks. Motor performance was assessed using the Sunnybrook Facial Grading System (SFGS), functional disability with the Facial Disability Index (FDI), and anxiety with the Beck Anxiety Inventory (BAI), at baseline (T0) and post-treatment (T1). Non-parametric and Bayesian analyses were conducted to evaluate between/within-group differences. Fourteen patients [SURGICAL: n = 7, age (mean ± SD) = 50.57 ± 18.17, 3F; NON-SURGICAL: n = 7; age (mean ± SD) = 51 ± 11.61, 3F)] completed the intervention with no dropouts. In between-group comparison, NON-SURGICAL group significantly increased the Synkinesis Score in SFGS (p = 0.019, BF₁₀ = 1.903), whereas SURGICAL group increased the FDI – Physical Function subscale (p = 0.002, BF₁₀ = 5.033) and in the FDI – Social/Well-being Function subscale (p = 0.004, BF₁₀ = 3.743) score. In within-group comparison SURGICAL group significantly improved the Resting Symmetry Score in SFGS (p = 0.032, BF₁₀ = 9.262), BAI (p = 0.022, BF₁₀ = 66.338), Symmetry of Voluntary Movement Score in SFGS (p = 0.022, BF₁₀ = 23.300), Composite SFGS Score (p = 0.016, BF₁₀ = 24.859), FDI – Physical Function subscale (p = 0.021, BF₁₀ = 24.550) and FDI – Social/Well-being Function subscale (p = 0.034, BF₁₀ = 10.664); similarly, NON-SURGICAL group improved the Symmetry of Voluntary Movement Score in SFGS (p = 0.034, BF₁₀ = 6.261) and Composite SFGS Score (p = 0.034, BF₁₀ = 6.288). However, for NON-SURGICAL group, a significant increase in the Synkinesis Score in SFGS (p = 0.034, BF₁₀ = 4.964) was also disclosed. ET appears to be a clinically relevant PT approach for peripheral FNP, with etiology-specific response patterns that likely reflect differences in underlying neuroplastic mechanisms. ET is suited for hybrid and telerehabilitation models, supporting its integration into digitally enabled rehabilitation pathways. However, these preliminary findings require confirmation in larger, controlled studies. not applicable.

BACKGROUND:The amyloid-β peptide 42 (Aβ42) forms fibrillar aggregates that are a hallmark of Alzheimer's disease. While recent therapeutic strategies targeting Aβ42 fibrils and oligomers have shown promise, safer and more effective interventions are still needed. Noninvasive brain stimulation (NIBS) techniques such as repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) have emerged as potential complementary approaches, yet the molecular mechanisms by which electric fields influence amyloid aggregation remain poorly understood. METHODS:We performed atomistic molecular dynamics simulations to investigate the response of Aβ42 fibrils to static electric fields of increasing strength. Simulations were based on an ex vivo fibril structure with reconstructed N-terminal regions, and different structural restraint conditions were used to disentangle surface and core effects. RESULTS:Electric fields perturb the disordered N-terminal 'fuzzy coat', altering its conformational dynamics and weakening its interactions with the fibril core, thereby modifying the fibril surface properties. Simulations with unrestrained fibril ends further reveal increased fluctuations in core residues, indicating field-induced destabilization that may hinder elongation. CONCLUSIONS:These findings provide molecular-level insight into how static electric fields can modulate amyloid fibril formation and propagation, offering a possible mechanistic basis for the effects of tDCS and related brain stimulation techniques.

Transcranial direct current stimulation (tDCS) on the prefrontal and posterior parietal cortex can enhance mental rotation (MR) performance, whereas little is known about cerebellar tDCS (ctDCS). This study aimed to evaluate effects of ctDCS on a MR task. Fifty-five healthy subjects were randomly assigned to active-ctDCS (1.5 mA; 20 min; n = 28) or sham-ctDCS (n = 27). Participants performed a MR task before (T0) and after (T1) stimulation. In each trial, two shapes appeared on a computer screen, one randomly rotated by 0, 45, 90, or 135 degrees. Subjects pressed the A or L key to indicate whether the shapes were identical or mirrored. A linear mixed model was run on the reaction times (RTs) recorded in each trial. Percent change in RTs (

Background: Chronic pain syndromes such as fibromyalgia have been associated with worsening health-related quality of life and increased incidence of comorbid psychiatric disorders, underscoring the need for targeted interventions. Transcutaneous spinal direct-current stimulation (tsDCS) and exercise therapy (ET) have been identified as promising non-pharmacological tools due to their capacity to inhibit pain transmission. However, empirical evidence regarding a combined efficacy remains limited. The aim of this work was, therefore, to test the effects of a multimodal treatment protocol on pain and psychological symptoms. Methods: Forty-five patients with fibromyalgia were recruited and randomly assigned to the tsDCS, ET, or combined tsDCS + ET group for a three-week period. Participants were assessed at baseline, one week after the start of treatment, at the end of the treatment (T2), and at 3-month follow-up (T3) using the Visual Analogue Scale (VAS), Brief Pain Inventory (BPI), Short-Form Health Survey (SF-12), and Hospital Anxiety and Depression Scale (HADS). Results: Analysis of variance applied to linear mixed-effect models showed significant group-by-time interaction effects on both HADS domains (anxiety: p = 0.004; depression: p = 0.028). Post hoc pairwise comparisons highlighted that tsDCS + ET decreased subjects’ anxiety at both T2 (p = 0.002) and T3 (p < 0.001) compared to baseline. Yet, significant comparisons were not found for depression. No significant interactions were detected on VAS, BPI, and SF-12 scores. Conclusions: Although between-group differences were not observed, the integration of neuromodulation with physical activity resulted in a significant improvement in patients’ anxiety-related symptoms severity, suggesting a potential added benefit.

Introduction: Multiple Sclerosis (MS) is frequently associated with a range of neurological, cognitive and psychological issues, presenting significant challenges to patients' Quality of Life (QoL). Among non-invasive neuromodulation techniques, transcutaneous spinal Direct Current Stimulation (tsDCS) is emerging as a potential approach for symptom management in neurological conditions. However, the effects of tsDCS on MS remain poorly explored. Thus, this preliminary study aimed to evaluate the effects of tsDCS on MS symptomatology, focusing on cognitive and psychological variables. Methods: Six patients with MS were recruited for a randomized, sham-controlled, double-blind crossover study, and received anodal tsDCS or sham stimulation in two separate sessions at least one month apart. Assessment outcomes included cognitive and attentional-executive functions, depressive symptoms, and several QoL components. The tests were administered at baseline (T0), immediately after treatment (T1), one week (T2) and one month (T3) post-treatment. Results: Although protocol-by-time interactions did not reach statistical significance across all measures, protocol-independent improvements over time were observed in various QoL subscales, including Physical Functioning, Role Limitations due to Physical Health, Vitality, Health Distress, and Overall QoL. Conclusions: Our findings indicate that tsDCS is a feasible and well-tolerated intervention in patients with MS, with possible implications for QoL. Given the small sample size and the exploratory nature of this study, further research is needed to clarify whether tsDCS may represent a potentially beneficial non-invasive neuromodulation approach for improving well-being in patients with MS across both physical and mental dimensions.

Air pollution is linked to an increased risk of multiple sclerosis (MS) in adults. To investigate the link between air pollutant exposure and pediatric MS (pedMS) in an Italian cohort. PEDIGREE (Pediatric Italian Genetic and Environment Exposure) is a multicenter case–control study investigating genetic and environmental factors in MS before the age of 18. Information on environmental and perinatal exposures was collected through the PEQ-IT questionnaire. Air pollution data during the first, second, and third years prior to MS onset (PM2.5, PM10, O3, NO2, SO2, and CO levels) were obtained from the European Monitoring and Evaluation Program database. Data were available for 113 pedMS cases and 117 controls. We found statistically significant associations between pedMS and higher exposure to ozone (O3) in the first (OR = 1.11; 95

BACKGROUND:Multiple sclerosis (MS) treatment response varies significantly, hindering effective management and necessitating better predictive biomarkers. Pharmacogenomics offers a promising avenue to identify genetic markers that, combined with clinico-demographic predictors, could enhance personalized therapeutic decisions. OBJECTIVES:This multi-center study investigated genetic determinants of response to interferon-beta (IFN-β) and glatiramer acetate (GA) in European ancestry patients with relapsing-remitting MS (RRMS). METHODS:After harmonization and quality control, we tested over 6 million genetic variants. We used negative binomial regression, meta-analysis, and gene-set enrichment to link variants, genes, and biological pathways to treatment response. RESULTS:In 679 GA and 1614 IFN-β patients, the top GA variant was rs2053696A in MAP3 K1 (p = 3.97*10-9), involved in key signaling pathways. Another significant GA signal was in WWOX. For IFN-β, no genome-wide significant variants were found, but suggestive signals emerged near ZMIZ1, ZCCHC7, and other genes linked to immune function and interferon signaling. Gene-set analysis revealed IL-17 regulation for GA and ion channel pathways for IFN-β. CONCLUSION:This study identified novel genetic variants for GA response, implicating genes in crucial pathways. For IFN-β, suggestive signals point to immune and interferon-related genes. These findings enhance our understanding of genetic influences on RRMS treatment response, while highlighting pharmacogenomic research challenges.

Introduction:Precise identification of motor states in Parkinson's disease (PD) is critical for adaptive deep brain stimulation (aDBS) therapies. Recent developments in implantable neurostimulators now support continuous neural recordings, enabling long-term monitoring of PD-related neural dynamics under real-world conditions. However, the real potential of such deep brain continuous recordings in chronic home-based conditions has not been explored yet. In this work, we introduce a multimodal classification framework that integrates subthalamic nucleus local field potentials (STN-LFPs), wearable sensors, and patient-reported diaries to distinguish between three key motor states: ON, OFF, and SLEEP. Methods:The framework was initially validated on data collected from three patients over an average of 30 days (totaling 2,136 h of LFP recordings), and then applied to a larger dataset from thirteen patients recorded over an average of 14 days (totaling 4,440 h of LFP recordings). Feature extraction was performed in the time, frequency and time-frequency domains, after applying principal component analysis (PCA) to decrease dimensionality, which preserved 95% of the variance of the data and reduced computational complexity. Results:The multilayer perceptron (MLP) classifier using time-frequency domain features achieved the highest F1-score among the models tested. For the three validation patients, the MLP reached F1-scores of 81.1% with wearable sensor data and 94.3% with diary-derived data. When evaluated across all thirteen patients, it maintained a strong F1-score of 93.1% using diary time-frequency features. Discussion:These results demonstrate that chronic LFP recordings available 24/7 from implantable aDBS devices enable robust motor state classification, thus supporting the personalization and optimization of aDBS systems for real-life use.

OBJECTIVES:Chronic pain significantly impacts quality of life. Headache and fibromyalgia are common chronic pain disorders, often linked to cognitive, emotional, and social impairments. This study examined the associations between pain, related symptoms, and psychosocial outcomes in individuals with chronic headache and fibromyalgia. METHODS:A cross-sectional online study was conducted on 42 participants: 21 with chronic headache and 21 with fibromyalgia. Data were collected on pain intensity and interference (Numeric Rating Scale, Brief Pain Inventory) and psychosocial variables (Pain Self-Efficacy Questionnaire, Pain Catastrophising Scale, 12-Item Short Form Survey). RESULTS:Headache participants reported moderate pain intensity (mean NRS=5.5, SD=2.3), with BPI intensity significantly correlated with general activity (r=0.621, p=0.003), mood (r=0.730, p=0.001), and self-efficacy (r=0.515, p=0.017). Specific symptoms such as motor (rs=0.682, p=0.001) and sensory deficits (rs=0.541, p=0.011) were strongly associated with PCS rumination. In the fibromyalgia group, pain intensity was higher (mean NRS=7.38, SD=2.2) and correlated with PCS total (r=0.606, p=0.004), helplessness (r=0.777, p<0.001), and interference with daily life (r=0.823, p<0.001). Mental health (SF-12 MCS) was negatively associated with pain in fibromyalgia but not in headache. CONCLUSIONS:While both conditions are linked to psychosocial impairment, fibromyalgia was associated with higher pain intensity and stronger correlations with psychological dysfunction, while chronic headache showed more selective associations, particularly involving perceived interference with mood and ruminative thinking.

BackgroundPeripheral facial nerve palsy is a debilitating condition that may necessitate surgical intervention. Although motor rehabilitation is considered essential, the most effective approach has not yet been determined. ObjectiveThis study aimed to evaluate the feasibility and effectiveness of emotional training, a novel telerehabilitation-based treatment, on motor, functional, and psychological outcomes in patients with unilateral facial palsy following triple innervation surgery. MethodsA prospective, assessor-blinded, 2-arm pilot cohort study was conducted at the rehabilitation unit at University Hospital San Paolo, Milan, Italy, from January to October 2024. Participants (N=16) received 1 treatment session every 2 weeks over 20 weeks, each lasting 45 minutes, according to standard clinical procedures in place at the rehabilitation unit. Participants were nonrandomly assigned to either an in-person group (n=8) or an online group (ie, telerehabilitation; n=8) based on their ability to attend in-person sessions. The primary outcomes assessed at baseline (T0) and after treatment (T1) included facial symmetry (Sunnybrook Facial Grading System; SFGS), facial disability (Facial Disability Index; FDI), and anxiety levels (Beck Anxiety Inventory). ResultsStatistical analysis revealed significant improvements at T1 for both groups in the FDI social and well-being function subscale, Beck Anxiety Inventory, SFGS resting symmetry score, SFGS symmetry of voluntary movement score, SFGS composite score, SFGS with bilateral masseter contraction symmetry of voluntary movement score, and SFGS with bilateral masseter contraction composite score (P<.001 for all). Only the FDI physical function subscale showed a differential improvement at T1 for the in-person group treatment (ANOVA for time × treatment: F1=14.356; P=.002; Holm-Bonferroni post hoc test: P<.001). Finally, a strong positive correlation was observed between the time elapsed from surgery to rehabilitation and SFGS composite score improvement at T1 (r=0.94; P=.005). ConclusionsThese results suggest that the online emotional training protocol is as feasible and effective as the in-person emotional training protocol in improving facial motor function, reducing anxiety, and enhancing facial expression spontaneity in patients who had undergone surgery for peripheral facial palsy. These findings support the validity of telerehabilitation approaches as a feasible, accessible, and sustainable alternative to conventional in-person therapy for facial nerve recovery.

Transcranial direct current stimulation (tDCS) has been proposed as a non-invasive neuromodulatory strategy to enhance motor performance and modulate inflammatory responses. However, its effects on strength capacity and physiological stress markers during complex resistance exercises in elite athletes remain underexplored. In this exploratory, randomized, sham-controlled pilot study, ten elite male weightlifters (n = 10; active tDCS = 5, sham = 5) received either a single 20-min session of anodal tDCS (2 mA) over the motor cortex or sham stimulation immediately before performing high-load back squats (85

BACKGROUND:Oropharyngeal dysphagia is a common and disabling consequence of stroke. Transcranial direct current stimulation (tDCS) has shown potential in promoting swallowing recovery, although evidence remains limited. OBJECTIVE:To determine whether bilateral anodal tDCS combined with intensive speech-language therapy (SLT) improves swallowing outcomes compared with sham stimulation in patients with post-stroke dysphagia. Exploratory analyses examined the influence of treatment phase, sex, lesion site, and baseline severity. METHODS:This multicenter, randomized, double-blind, sham-controlled trial enrolled patients with supratentorial or infratentorial ischemic stroke and oropharyngeal dysphagia. Participants received either bilateral anodal tDCS or sham stimulation (1.5 mA, 20 min/day, 5 days/week for 2 weeks) combined with intensive SLT over 6 weeks. Swallowing outcomes were assessed at baseline, 2 weeks, and 6 weeks using the Dysphagia Outcome and Severity Scale (DOSS, primary outcome), Penetration-Aspiration Scale (PAS), Mann Assessment of Swallowing Ability (MASA), and Swallowing Quality of Life questionnaire (SWAL-QoL). RESULTS:Forty-six patients (24 active, 22 sham) completed the protocol. Both groups showed significant improvement across all outcomes (p < 0.001), with no significant difference between active and sham stimulation. The DOSS was the most sensitive measure, showing sustained improvement over time. Exploratory analyses indicated greater MASA gains with active tDCS in infratentorial strokes (p = 0.04). Correlation analyses showed that greater baseline dysphagia severity was associated with larger functional gains. CONCLUSIONS:Intensive SLT was associated with meaningful recovery in post-stroke dysphagia, regardless of stimulation condition. Exploratory findings suggest that bilateral tDCS may confer additional benefit in selected lesion subgroups.

Background and Objectives:As artificial intelligence (AI) rapidly becomes an integral tool in clinical neurology, future clinicians will need to master its application in patient care. While previous studies focused primarily on medical students' perspectives, our survey, addressed to Italian neurology residents, aims to assess their familiarity with AI tools and identify educational needs of learners close to clinical practice and care delivery. Methods:A cross-sectional, web-based survey designed by the University of Milan was distributed nationwide to neurology residents from May 22 through July 30, 2025. The questionnaire included items on demographics, self-assessed AI knowledge, exposure to AI training, clinical applications, perceived challenges, and attitudes toward the impact of AI on neurology practice. Descriptive statistics and association analyses were performed. Results:A total of 173 residents (12.7%) completed the survey, with 37% affiliated with research hospitals. Although AI is frequently used in practice, with 40.7% using AI tools at least on a weekly basis, only 30.7% rated their knowledge as "good" or higher. Paradoxically, most residents (79.2%) reported no curriculum-integrated AI education, which was instead significantly associated with geographical background (Χ2 = 45.36, p < 0.001), while nearly all respondents expressed interest in further AI training (93.1%). The most familiar application was generative AI for clinical decision support (64.2%), and neuroimaging was rated as the first AI integration area (mean priority 2.99). Main barriers to AI application included concerns about reliability (71.1%) and data privacy (43.9%). Regarding career perspectives, 41.6% of residents believed that AI will create new job opportunities, whereas most (89%) agreed that the AI revolution will not replace human professionals. Discussion:Despite the limited number of participants, our survey provides a representative snapshot of AI knowledge, use, and attitudes among neurology residents in Italy, a critical country in the digital health care transformation, contributing important evidence for international shared recommendations on AI educational needs to support future clinical practice. Although AI tools are widely used, most residents had only basic knowledge and limited formal training, prompting calls for more structured, learner-centered educational modules to be integrated into neurology curricula.

Background Transcranial ultrasound (tUS) represents a promising brain stimulation technique, yet its physiological effects using standard diagnostic protocols remain poorly characterized. This study examines the impact of conventional diagnostic ultrasound (dUS) on intracortical excitability. Methods Healthy subjects received 30 minutes of transcranial ultrasound (2.0 MHz) over the right motor cortex. Cortical excitation and inhibition were assessed bilaterally via paired-pulse TMS, quantifying resting motor threshold (RMT), short intracortical inhibition (SICI), intracortical facilitation (ICF) and long intracortical inhibition LICI before and after stimulation. The vasomotor reserve (through the breath-holding index) was also assessed. A computational model was developed to confirm the spatial selectivity of our protocol. Non-parametric and Bayesian analyses were used. Results Sixteen healthy adults (mean age 31.9 ± 11.0 years) were enrolled. dUS induced a significant reduction in SICI in the stimulated hemisphere (p = 0.016; Bayes Factor BF = 7.65), and a robust increase in LICI in the control hemisphere (p = 0.010; BF = 7.88). Between hemispheres, SICI was higher in the stimulated than in the control side (p = 0.046; BF = 3.90), while LICI was greater in the control hemisphere (p = 0.015; BF = 10.06). ICF, RMT and BHI showed no significant changes (all p > 0.05). Conclusions dUS elicits focal changes in cortical excitability, towards an overall excitatory effect, in the absence of detectable vascular changes. The observed changes also engage compensatory transcallosal mechanisms, likely involving GABA-B-mediated pathways within the contralateral hemisphere. These findings provide mechanistic evidence supporting further translational investigation.