SET Domain Containing 1A (SETD1A) is a histone H3K4 methyltransferase implicated in neurodevelopmental disorders. Pathogenic variants in this gene are associated with schizophrenia, intellectual disability, and epilepsy. Here, whole-exome sequencing and Sanger sequencing were performed on a 4-year-old Chinese girl with early-onset epilepsy and her unaffected parents. A novel de novo heterozygous variant in SETD1A (NM_014712.3: c.1067C > T/p.Ser356Phe) was identified in a patient presenting with focal-to-bilateral tonic–clonic seizures, beginning at 3 months of age. Neuroimaging revealed a normal brain MRI, and comprehensive neuropsychological assessment indicated preserved cognitive function. The variant was absent in 200 local controls and classified as likely pathogenic per ACMG criteria. This study may expand the mutation and phenotypic spectrum of SETD1A-related disorders, establishing the relationship between SETD1A variants and isolated early-onset epilepsy without accompanying severe neurodevelopmental deficits, highlighting the value of genetic testing in infants with unexplained epilepsy.
Altered brain entropy and functional connectivity patterns in peritoneal dialysis patients
ObjectiveTo explore abnormal changes in brain entropy (BEN) and resting-state functional connectivity (RSFC) in peritoneal dialysis (PD) patients and their associations with cognitive impairment (CI).MethodsFifty-three PD patients and 49 age-, gender-, and education-matched healthy controls (HCs) were enrolled. Resting-state functional magnetic resonance imaging (rs-fMRI) was performed to calculate BEN and RSFC. Neuropsychological assessments and clinical indicator collection were conducted. PD patients were divided into mild cognitive impairment (MCI) and non-cognitive impairment (NCI) groups using Montreal Cognitive Assessment (MoCA) scores. Correlation analyses were performed between BEN/RSFC values and neuropsychological/clinical indicators.ResultsPD patients exhibited significantly poorer performance in multiple cognitive scales than HCs (all p < 0.001). Compared with HCs, PD patients had decreased BEN in the right middle occipital gyrus and left caudate nucleus, and increased BEN in the left middle temporal gyrus and right fusiform gyrus. Reduced RSFC was found between the right middle occipital gyrus and the right fusiform gyrus, right middle frontal gyrus, and right precuneus in PD patients. BEN and RSFC values were correlated with emotional scale scores, cognitive scale subscores, and clinical indicators (e.g., glycosylated hemoglobin, transferrin saturation).ConclusionPatients with end-stage kidney disease undergoing peritoneal dialysis present abnormal brain entropy and functional connectivity patterns. These alterations are associated with systemic metabolic disorders, long-term dialysis treatment, and cognitive/emotional impairment.
An end-to-end pipeline for automated fetal brain segmentation and biometry from 3D SSFP MRI
Fetal magnetic resonance imaging (MRI) plays an essential role for the evaluation of fetal abnormalities, offering improved visualization of developing brain structures and superior soft tissue contrast in comparison to other imaging modalities. Accurate and reproducible assessment of fetal brain biometry is critical for diagnosing neurodevelopmental abnormalities. However, these measurements typically rely on manual segmentation, which is time-consuming, labor-intensive, prone to error and dependent on the interpreting radiologist’s expertise and experience. Recent advancements have enabled automated analysis primarily on Half-Fourier Acquisition Single-shot Turbo spin-Echo (HASTE) sequences, yet these acquisitions are susceptible to inter-slice misalignment and often require time-consuming super-resolution reconstruction. In contrast, 3D Steady-State Free Precession (SSFP) imaging offers smaller slice thickness, improving through-plane resolution, along with reduced motion sensitivity and whole-body coverage in a single scan. In this study, we present an end-to-end deep learning pipeline for automated segmentation and biometry of the fetal brain from whole-body SSFP MRI. The dataset includes manual annotations of the fetal head, brain parenchyma and extraaxial cerebrospinal fluid (CSF). The framework employs nnU-Net for robust head localization and multi-structure segmentation, along with principal component analysis (PCA)-based reorientation and head circumference estimation. A Tri-Attention U-Net architecture was evaluated as a standalone model and within the nnU-Net framework. The final pipeline consists of a Tri-Attention nnU-Net for head localization and nnU-Net for multi-structure segmentation. The pipeline achieved mean Dice similarity coefficients (DSC) of 94.48, 93.58 and 82.75% for the head, brain parenchyma and extraaxial CSF, respectively. These findings demonstrate the feasibility of accurate, fully automated fetal brain biometry from SSFP MRI with potential to reduce inter-observer variability, streamline clinical workflows and enhance clinical decision-making through fast and reproducible quantitative assessment.
Local field potentials for target localization in centromedian deep brain stimulation for epilepsy
ObjectiveTo evaluate whether local field potential (LFP) spectral profiles can serve as a candidate “spectral fingerprint” for physiological confirmation of centromedian-parafascicular (CM–Pf) targeting during thalamic deep brain stimulation (DBS) for drug resistant epilepsy (DRE).MethodsThis is a retrospective study of 10 patients (20 leads) who underwent CM-DBS implantation for DRE at a single tertiary center. Postoperative CT and preoperative MRI were co-registered, normalized to the Montreal Neurological Institute (MNI) space, and reconstructed using Lead-DBS software to anatomically localize contacts. BrainSense™ Survey recordings were obtained at least 3 weeks post-implant during routine programming. LFP frequency content was analyzed, and prominent peaks were identified and classified into canonical frequency bands (theta, alpha, beta). These spectral profiles were then mapped to MRI-based anatomical localizations, and statistical tests were applied to assess associations between peak patterns, contact localizations and thalamic subregions.ResultsContacts were distributed as follows: 50 in the CM, 16 in the Parafascicular (Pf), 15 in the Centrolateral, 8 in the Mediodorsal, and 7 in the Ventrolateral (VL) nuclei. Of the 10 representative spectral localizations confined to the CM/CM-Pf region, 8 (80%) displayed a distinct dual-peak spectral profile with peaks in the theta/low alpha (5.5–9 Hz) and high beta (20–30 Hz) bands (mean frequencies: 7.63 Hz and 21.02 Hz, Fisher’s exact test, p < 0.001). Single-peak profiles showed no significant association with specific nuclei (p = 0.871). Contacts overlapping other thalamic nuclei more frequently exhibited narrow 10–15 Hz peaks (p = 0.005) or triple-peak profiles (p = 0.02), suggesting mixed structural contributions.ConclusionA dual- band candidate spectral pattern consisting of theta/low alpha and high beta peaks was associated with the CM-Pf region in this cohort. This finding provides early evidence supporting the feasibility of incorporating passive LFP recordings as a physiologic marker of target engagement. Future work to prospectively compare bipolar survey-based localization with monopolar recording strategies could enable development of a state-based, physiologically informed spectral atlas to refine CM-Pf targeting in thalamic neuromodulation for DRE.
Freezing of gait and the effects of vibrotactile cueing in Parkinson’s disease–a study protocol of a cross-sectional multimodal brain imaging approach in virtual walking scenarios
BackgroundFreezing of gait (FOG) is one of the most debilitating motor symptoms in Parkinson’s disease (PD), affecting a substantial proportion of people with PD. Numerous hypothetical mechanisms exist, attempting to explain FOG. Current evidence originated from stationary measures in lying positions, limiting the understanding of neurophysiological changes elicited by FOG episodes during regular locomotion. Neurophysiological aspects of FOG, especially in response to vibrotactile cueing, have been explored only by a few studies. To address this gap, the current study aims to investigate FOG episodes in people with PD and the impact of vibrotactile cueing while walking through virtual environments on a self-paced treadmill.MethodsThirty people with Parkinson’s Disease and FOG will be recruited. They will undergo screening and familiarization before performing different walking tests in virtual reality using the Gait Real-time Analysis Interactive Lab (GRAIL). Participants will perform two experimental blocks, each consisting of four walking trials of approximately 10 min. A break of 10 to 30 min will be provided between blocks. Walking with or without vibrotactile cueing will be performed in alternation. During walking, electrocortical (EEG), hemodynamic (fNIRS), kinematic data (3D motion capture), and kinetic data (force plates) will be recorded. Data will be analyzed to investigate spatiotemporal and frequency characteristics of electrocortical and hemodynamic brain activity related to FOG and the impact of vibrotactile cueing on neural signatures and gait improvements in FOG.DiscussionCombining neurophysiological measurements of EEG and fNIRS paired with kinematics and kinetics will provide insights into the cortical and behavioral changes associated with FOG and vibrotactile cueing, to derive results that can be used for the design of intervention strategies for treating PD.Study protocol registrationhttps://drks.de/search/de/trial/DRKS00034584, identifier DRKS00034584.
Autistic- and attention-deficit/hyperactivity disorder-like traits: differential associations with burnout, depression and anxiety, and empathy among Japanese junior residents
IntroductionBurnout, depression, and anxiety are major concerns among physicians because they affect individual well-being, patient care, and healthcare systems. Neurodevelopmental traits, including autistic-like traits (ALTs) and attention-deficit/hyperactivity disorder (ADHD)-like traits (ADHLTs), may increase vulnerability to psychological distress. However, little is known about how these traits relate to burnout, depression and anxiety, and empathy among junior residents.MethodsIn this cross-sectional study, 148 junior residents from two teaching hospitals in Japan completed validated measures of ALTs (21-item Japanese version of the Autism-Spectrum Quotient), ADHLTs (Adult ADHD Self-Report Scale Screener), burnout (Maslach Burnout Inventory), depression and anxiety (Hospital Anxiety and Depression Scale), physician–patient empathy (Jefferson Scale of Physician Empathy), and psychological flexibility and inflexibility processes (Valuing Questionnaire, Cognitive Fusion Questionnaire-7, and Work-related Acceptance and Action Questionnaire). Associations were examined using multivariable logistic and linear regression analyses. Exploratory statistical mediation analyses using structural equation modeling examined indirect associations through psychological flexibility and inflexibility processes.ResultsThe prevalence of ALTs and ADHLTs was 23.6% for each trait. ALTs were associated with lower personal accomplishment, a burnout dimension; higher depression and anxiety; and lower physician–patient empathy. ADHLTs were associated with greater emotional exhaustion, another burnout dimension. In exploratory statistical mediation analyses, progress toward values, a core process of psychological flexibility, showed a significant indirect association between ALTs and personal accomplishment, and the direct association was attenuated and no longer statistically significant after including the process variables. Significant indirect associations through progress toward values were also observed for the associations of ALT with depression and anxiety and empathy. Cognitive fusion, a core process of psychological inflexibility, showed a significant indirect association between ADHLTs and emotional exhaustion. Overall, neurodevelopmental traits were associated with distinct patterns of psychological functioning, suggesting variability in both vulnerability and adaptive processes.DiscussionNeurodevelopmental traits such as ALTs and ADHLTs were significantly associated with burnout dimensions, depression and anxiety, and physician–patient empathy among junior residents. Psychological flexibility and inflexibility processes, particularly progress toward values and cognitive fusion, may be relevant to these associations. Process-based support strategies may warrant further investigation for residents with elevated neurodevelopmental traits.Clinical trial registrationhttps://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R00005, identifier UMIN000046897.
Treating addiction with an addictive drug: the ketamine paradox revisited
BackgroundSubstance use disorders (SUDs) and treatment-resistant depression (TRD) remain a major global health challenge, marked by high relapse rates and limited long-term effectiveness of existing treatments. Ketamine, a glutamatergic modulator with rapid neuroplastic effects, has emerged as a novel intervention for TRD and is increasingly investigated as an adjunctive treatment for addiction, yet concerns about its abuse liability persist.ObjectiveThis review critically evaluates ketamine’s therapeutic potential for SUDs while examining its neurobiological mechanisms, clinical efficacy, and risk of misuse within a unified risk–benefit framework.MethodsA structured narrative review conducted in accordance with the SANRA framework using the PubMed, Scopus, PsycINFO, and Web of Science databases, covering literature published until March 2026. Eligible studies included clinical trials, experimental studies, and mechanistic investigations relevant to ketamine use in addiction and depression. Evidence was synthesized thematically across the domains of efficacy, mechanisms, and safety.ResultsAcross alcohol and cocaine use disorders, ketamine combined with psychotherapy has demonstrated promising reductions in craving and increases in abstinent days in small-to moderate-sized Phase 2 trials. However, findings remain difficult to generalize due to considerable variability in dosing strategies, comparator conditions, and follow-up periods. Effects on relapse prevention have been more inconsistent and less reliably positive. Mechanistically, ketamine promotes synaptic plasticity via NMDA receptor antagonism and downstream glutamatergic signaling, potentially disrupting maladaptive reward-related memories and reversing maladaptive neurocircuitry involved in both depression and addiction. While acute adverse effects are generally transient under clinical supervision, ketamine carries a well-established risk of misuse, particularly in unsupervised or high-dose settings.ConclusionsKetamine represents a promising but still experimental intervention for both refractory depression and selected SUDs. Its clinical use depends on careful patient selection, structured delivery, and integration with psychotherapy. Although ketamine may redefine treatment paradigms for TRD and addiction, larger-scale trials and long-term safety data are essential to define its role within psychiatric and addiction treatment frameworks.
Loneliness, rumination, and adolescent psychological crisis in China: a pilot moderated mediation study
BackgroundAdolescent psychological crisis—encompassing depressive disorder, anxiety disorder, and suicidal ideation—is a major public health challenge. One in five adolescents experiences a clinically significant mental health condition globally. Loneliness is a well-documented, modifiable risk factor for these outcomes. However, the exact cognitive-emotional pathways linking loneliness to acute psychological crisis remain unclear. This is particularly true in China, where rapid social change and intense academic pressure increasingly strain adolescent mental health. We do not yet fully understand how protective resources might buffer these specific pathways.Objectives and methodsThis pilot study tests a moderated mediation model based on the Evolutionary Theory of Loneliness and the stress-vulnerability framework. We investigate ruminative thinking as a cognitive-emotional mediator between loneliness and psychological crisis. We also test whether perceived social support and psychological resilience moderate distinct stages of this pathway. Based on a pilot sample of N = 312 Chinese adolescents (ages 12–18), we use structural equation modelling (SEM), confirmatory factor analysis (CFA), and Hayes’ PROCESS Macro (Model 14) with 5, 000 bootstrap replications. Two-wave longitudinal data (n = 187, 8-week interval) were available for the depression outcome only; the anxiety and suicidal-ideation pathways were examined cross-sectionally.ResultsLoneliness is significantly associated with depressive symptoms (β = 0.43, p < 0.001), anxiety (β = 0.38, p < 0.001), and suicidal ideation (β = 0.27, p < 0.001). Ruminative thinking accounts for 40–46% of the total indirect association across all three outcomes. Social support buffers the transmission from loneliness to rumination (b = −0.16, p = 0.002, ΔR2 = 0.023), while resilience buffers the transmission from rumination to crisis (b = −0.19, p < 0.001, ΔR2 = 0.031).ConclusionsThese preliminary, exploratory findings are consistent with the possibility that ruminative thinking partially accounts for the cross-sectional association between loneliness and adolescent psychological crisis in China, and with social support and resilience attenuating this association at potentially distinct stages. Because the pilot is underpowered for the moderated mediation model and the available longitudinal evidence covers depression only, the moderation and stage-specificity results should be read as hypothesis-generating rather than confirmatory. A planned full-scale study (N ≥ 1, 200) will test these mechanisms further. We also outline initial practical implications for school-based interventions.
Real-world outcomes of intranasal esketamine and intravenous ketamine induction therapy for treatment-resistant depression in a community clinic: a retrospective cohort study
IntroductionIntravenous (IV) ketamine and intranasal esketamine are NMDA receptor antagonists used for treatment-resistant depression (TRD). Both have demonstrated efficacy in controlled trials, but observational evidence from real-world community settings is limited.MethodsWe conducted a single-center retrospective cohort study of adults aged 18 to 65 receiving induction therapy for TRD with intranasal esketamine or IV ketamine at a community psychiatric clinic from January 1 through December 31, 2025. Patients with prior exposure to either medication or to oral ketamine derivatives were excluded. The primary outcome was change in Patient Health Questionnaire-9 (PHQ-9) score from baseline to end of induction. Secondary outcomes included response (≥50% PHQ-9 reduction), remission (final PHQ-9 ≤4), clinically meaningful improvement (≥5 PHQ-9 reduction), induction completion, and adverse events. Within-group and per-protocol analyses were exploratory.ResultsSixty-three patients met inclusion criteria (esketamine n=37; IV ketamine n=26). Baseline PHQ-9 scores were similar (18.22±4.49 vs. 18.27±5.41; P = 0.967), as was mean change from baseline (-10.31±5.59 vs. -9.50±5.69; mean difference 0.81, 95% CI -2.12 to 3.75; P = 0.589). Response rates were 64.9% vs. 69.2% (RR 0.94, 95% CI 0.66 to 1.33; P = 0.790), remission 32.4% vs. 23.1% (RR 1.41, 95% CI 0.61 to 3.26; P = 0.573), and clinically meaningful improvement 83.8% vs 73.1% (RR 1.15, 95% CI 0.87 to 1.51; P = 0.353). Induction completion exceeded 90% in both groups; one patient per cohort discontinued from intolerable side effects, and no serious adverse events occurred. Within-group PHQ-9 reduction was large: 10.31±5.59 points (paired t[34]=10.91; P<0.001; Cohen’s d=1.84) for esketamine and 9.50±5.69 points (paired t[23]=8.18; P<0.001; Cohen’s d=1.67) for ketamine. Findings remained statistically significant and clinically large under a pre-specified baseline observation carried forward (BOCF) sensitivity analysis (Cohen’s d=1.65 and 1.45).ConclusionsInduction therapy with intranasal esketamine and intravenous ketamine was associated with robust antidepressant effects in a community outpatient setting, consistent with prior trial data. The modest sample size limits power to detect between-group differences and increases the risk of type II error; the absence of statistically significant between-group differences should therefore not be interpreted as evidence of equivalence. Protocol asymmetry between arms (esketamine: 12 sessions over 8 weeks; IV ketamine: 6 sessions over 3 weeks) further limits direct comparison of endpoint values between groups. Practical considerations including insurance coverage, cost, and administration logistics may help guide treatment selection. Longitudinal follow-up is planned to characterize treatment durability.
Autism service barriers for Latine children and their families: a participatory approach to adapting autism diagnostic care
IntroductionLatine children from families with limited English proficiency (LEP) experience barriers to timely autism diagnosis resulting in persistent health inequities. This participatory mixed-methods study examined these barriers and identified multi-level strategies to adapt diagnostic care models for Spanish-speaking Latine families.MethodsParticipants included twelve caregivers of thirteen autistic children with parent reported diagnosis of autism, twelve clinicians, and six care coordinators. All participants completed surveys and participated in qualitative interviews or focus groups.ResultsQuantitative findings revealed significant lag between caregiver’s first developmental concern and diagnosis, limited autism knowledge, and difficulty navigating care. Qualitative results highlighted systemic barriers, including clinician-patient language discordance, interpreter inaccuracies and quality variability, cultural stigma, and long waitlists. Clinicians reported challenges with communicating about autism with Spanish-speaking families and emphasized language and cultural differences as primary barriers. Caregivers described social isolation, mistrust of health systems, and emotional distress compounded by immigration-related stressors.DiscussionFindings underscore the need for structural adaptation of care approaches beyond translation services.