Zhanxiang Wang

Motor learning transforms variable actions into reliable skilled behavior, but how premotor cortex supports this transformation remains unclear. We longitudinally recorded bilateral local field potentials and single-unit activity from the rat rostral forelimb area while animals acquired a single-pellet retrieval task. Here, we show that improved skill was accompanied by reduced, rather than increased, task-related premotor recruitment. Despite this attenuation, firing remained dominated by suppression around pellet retrieval, and stronger pre-retrieval suppression was associated with greater odds of successful performance. Population neural state analysis further showed that successful actions were most strongly coupled to sustained pre-retrieval engagement early in learning, whereas later success occurred with less population-level engagement. These findings reveal premotor cortical constraint as a population-level process that is progressively refined as motor learning transforms variable actions into reliable skilled behavior.

Background: Mpox, caused by monkeypox virus (MPXV), has emerged as a growing global health concern, yet effective targeted antiviral therapies remain limited. Thymidylate kinase (TMK), an essential enzyme required for viral DNA replication, represents a potential therapeutic target. Methods: We established a structure-based drug repurposing workflow integrating multi-pocket virtual screening and molecular dynamics (MD) simulations. A curated library of FDA-approved compounds was screened across five predicted TMK binding pockets, followed by consensus ranking based on cross-pocket recurrence and docking scores. Top candidates were further evaluated using multiple independent MD simulations to assess binding stability and conformational dynamics. Results: Phylogenetic and structural analyses indicated that MPXV TMK is highly conserved among orthopoxviruses while structurally distinct from the human homolog. Virtual screening identified several prioritized candidates, among which capmatinib (DB11791), nebivolol (DB04861), and tucatinib (DB11652) consistently ranked highly across multiple pockets. MD simulations showed that all systems approached relatively stable conformational regimes after the initial phase of the simulations. Notably, DB11791 exhibited lower ligand RMSD and more stable pocket retention across independent simulations. Free energy landscape analysis further suggested that DB11791 adopted a more confined low-energy conformational state compared to other candidates. Conclusion: These findings suggest that DB11791 may represent a promising TMK-targeting candidate. More broadly, the combined multi-pocket consensus screening and dynamic evaluation strategy provides a computational framework for antiviral drug repurposing. Further experimental validation is required to confirm the antiviral activity of these candidates.

Background: Transcranial magnetic stimulation (TMS), as a non-invasive neurostimulation technique, modulates neural activity by applying electromagnetic fields to specific areas of the brain. It is clinically used for several approved indications, including major depressive disorder, obsessive‑compulsive disorder, and migraine with aura, and is under active investigation for other neurological and psychiatric conditions. Accurate stimulation targeting is crucial for the effectiveness of TMS. Existing targeting methods, such as generic brain localization caps and the international 10–20 electroencephalogram (EEG) system, generally provide only rough localization, leading to significant targeting errors. In recent years, significant progress has been made in the application of mixed reality (MR) technology in medicine, particularly in surgical navigation, offering new ideas and possibilities for developing a simple, low-cost, and efficient TMS navigation system. Objective: This study proposes, for the first time, a portable MR navigation system for non-invasive neural modulation target localization. The aim is to evaluate its localization accuracy and operational efficiency in TMS through preclinical validation. This system seeks to provide a simple and high-precision localization solution for other non-invasive technologies, with the goal of improving localization accuracy and simplifying the operational workflow in clinical applications. Methods: The system is based on Microsoft HoloLens 2 and features three specifically designed interaction tools. Five different types of simulation head models were selected, and ten target points were set on each head model. CT scanning was used to obtain imaging data for each head model. Three researchers used the system to perform target localization and repeated the verification process by adjusting the head model posture (from standing to lying) to assess localization accuracy and efficiency. Results: The validation conducted by the three researchers showed the following results: In the standing position of the simulated head model, the measurement errors were 2.4 (IQR: 1.4–2.7) mm, 2.3 (IQR: 1.7–2.7) mm, and 2.6 (IQR: 1.9–3.0) mm, respectively. In the lying position of the simulated head model, the measurement errors were 1.9 (IQR: 1.6–2.4) mm, 2.0 (IQR: 1.4–3.0) mm, and 2.5 (IQR: 1.9–2.9) mm, respectively. There was a significant difference between researchers ( p < 0.05), but no significant difference within the same researcher ( p > 0.05). Conclusion: The TMS-Guide, based on mixed reality technology, is a portable and simple navigation solution that provides higher localization accuracy than traditional manual targeting. It shows promising potential for broader applications in non-invasive neural modulation and brain-computer interface fields.

Background: Preoperative risk communication is essential for shared decision-making (SDM) in neurosurgery; however, conveying complex neuroanatomy and surgical risks using traditional verbal explanations can limit understanding and contribute to dissatisfaction and medicolegal disputes. Augmented reality (AR) may provide patient-specific, interactive 3D visualization to support these conversations. Objective: This study evaluates whether AR-assisted preoperative risk communication improves objective understanding and other SDM-related outcomes, compared with communication supported by a conventional physical anatomical model within a standardized SEGUE-informed protocol. Methods: A prospective, single-center, randomized controlled trial was conducted with 62 neurosurgery communication recipients (patients when capable; otherwise, a legally authorized representative [LAR]). Patients were stratified by planned surgical approach (frontal, parietal, and occipital) and, within each stratum, were randomized into an experimental AR group and a control physical-model group. The primary outcome was postsession objective understanding, assessed by a multiple-choice knowledge questionnaire. Secondary outcomes were subjective understanding, communication satisfaction, pre-to-post anxiety changes, communication duration, and neurosurgeons’ communication skills from video recordings. Results: Of the 67 individuals screened, 62 communication recipients were enrolled and completed all assessments (patients, n=30; LARs, n=32; AR, n=32; and control, n=30). Objective understanding was higher with AR than with the physical model in the prespecified pooled comparison (P=.01). Communication satisfaction was also higher with AR (P<.001). There were no clear between-group differences in subjective understanding (P=.41), anxiety changes (ΔState-Trait Anxiety Inventory [ΔSTAI] Y-1, P=.37; ΔSTAI Y-2, P=.84), in-session face-to-face communication duration (excluding any presession AR technical preparation time; P=.73), or SEGUE scores (P=.60). Exploratory stratified analyses suggested larger comprehension gains with AR in the parietal and occipital approach strata. Conclusions: In a standardized preoperative SDM conversation, an integrated visualization-support package combining AR, patient-specific modeling, and interactivity improved neurosurgical decision makers’ objective understanding and satisfaction without prolonging in-session, face-to-face communication duration. Larger multicenter trials with longer-term outcomes are warranted to confirm effectiveness and to evaluate implementation and cost considerations. Trial Registration: ISRCTN Registry ISRCTN11483487; http://www.isrctn.com/ISRCTN11483487