Neuroelectronics Research Flanders

Nonconvulsive epileptic activity is common after acute brain injury and contributes to neuronal injury and poor outcomes. Although intracranial electroencephalography (iEEG) improves detection compared with surface EEG (suEEG), it currently relies on focal recordings of epileptic dynamics. We prospectively evaluated multielectrode iEEG strategies designed to achieve large-scale cortical and deep brain coverage in critically ill patients. In a prospective cohort of adults with acute brain injury requiring invasive neuromonitoring, we implemented four depth electrode-based iEEG techniques: three electrocorticographic approaches (open subdural, burr hole subdural, and foramen ovale) and one stereotactic (transcortical) approach. The primary objective was to establish and quantify the extent and durability of cortical recordings. Additional assessments included safety, feasibility, and management impact. Electrode localization was performed in MNI305 space, and recording longevity was assessed using Kaplan-Meier and Cox proportional hazards models. Thirty patients with severe brain injury underwent implantation of 64 electrodes (772 contacts), yielding 361 total iEEG recording days across heterogeneous etiologies and surgical settings. Multielectrode implantation enabled distributed sampling spanning multilobar frontoparietotemporal cortical clusters. Overall, 72% of electrodes sampled cortical convexity alone, whereas 28% incorporated deep targets, including mesial temporal and orbitofrontal regions. Recording durability differed by implantation strategy (log-rank p = .0002), with a mean combined iEEG-suEEG monitoring duration of 14.5 days per patient. Implantation was successful in >95% of electrodes, monitoring started within 24 h postoperatively in 88%, and the per-electrode risk of a causally related adverse event was 3.1%, without hemorrhagic complications. iEEG influenced treatment initiation or escalation in 32% of monitored patients. Multielectrode iEEG strategies enable durable, large-scale cortical sampling in acute brain injury while remaining feasible and safe in the intensive care unit. By shifting from focal to distributed spatial sampling, these approaches provide a conceptual framework for improving detection of epileptic activity in critically ill patients.

AimsThe optimal duration of antibiotic therapy in joint infection remains controversial, particularly as native joint septic arthritis and periprosthetic joint infection (PJI) differ substantially in pathophysiology, surgical management, and prognosis. While short antibiotic courses have been advocated for native joints after adequate drainage, prolonged therapy is often recommended for PJIs due to biofilm-related infection. This systematic review and meta-analysis of randomized controlled trials (RCTs) aimed to compare short- with long-course antibiotic strategies in both native and prosthetic joint infections.MethodsFollowing PRISMA guidelines, a systematic search was performed across PubMed, Embase, Web of Science, and the Cochrane Library. Only RCTs were included. Studies were assessed for inclusion using predefined population, intervention, comparison, outcomes, and study (PICOS) criteria. Meta-analyses were conducted using MedCalc, and treatment failures were analyzed using odds ratios (ORs) with 95% CIs.ResultsA total of 12 RCTs involving 1,414 patients (native 577; periprosthetic 837) were included, with six eligible for meta-analysis. For PJIs, long-course therapy (≥ 12 weeks) significantly reduced treatment failure compared with short courses (OR 2.04, 95% CI 1.18 to 3.54; p = 0.011), while complication and mortality rates were similar. In contrast, for native joints, short-course therapy (≤ four weeks) achieved comparable infection control with prolonged regimens (OR 1.347; p = 0.565) when combined with adequate surgical drainage, particularly in paediatric populations. Surgical strategy (e.g. debridement, antibiotics, and implant retention vs one- or two-stage exchange) influenced outcomes more than antibiotic duration alone.ConclusionOptimal antibiotic duration should be individualized based on joint type and surgical approach. Short courses are effective for native septic arthritis with proper drainage, whereas PJIs generally require extended therapy due to biofilm-related complexity. We propose the Age-Joint-Immunity-Surgery-Sensitivity (AJISS) score as a decision-making tool to guide treatment duration, warranting prospective validation.Cite this article: Bone Jt Open 2026;7(3):394–406.

Elizabeth Casson Trust Research Grant_2022 (UK); Health Research Board (Ireland) & HSC Public Health Agency (Grant ESI-2021-001) through Evidence Synthesis/Cochrane Ireland REGISTRATION: Protocol DOI 10.1002/14651858.CD015371.

Alzheimer’s disease (AD) and frontotemporal dementia (FTD) are two major causes of dementia, with overlapping clinical and pathophysiological characteristics. We investigated whether resting-state EEG functional connectivity could distinguish AD, FTD, and healthy controls (HC) using a stacked ensemble learning approach. A publicly available dataset (openneuro.org/datasets/ds004504) was used to extract multiple connectivity metrics across frequency bands. Base classifiers were trained using the Fisher’s Geodesic Minimum Distance to Mean (FgMDM) approach with Euclidean or Riemannian distance metrics, and a meta-classifier was trained on their cross-validated predictions. Using leave-one-subject-out cross-validation, the stacked model achieved ROC-AUC values of 81.80% and 71.36% for distinguishing AD and FTD from HC, respectively. This was lower than the best single-base classifier performance, where several connectivity metrics achieved ROC-AUC values of 85% or higher for distinguishing AD and FTD. AD-FTD discrimination proved most challenging (ROC-AUC of 65.10%), suggesting overlapping network disruptions that limit separability. Classification performance was highest in the alpha band when distinguishing AD and FTD from HC, whereas the highest performance for distinguishing AD from FTD was observed in the delta band. Overall, these findings highlight the potential of EEG connectivity features for dementia classification and emphasize the importance of careful feature engineering and low-complexity models in the case of small-sample datasets.

Sensitive quantification of adeno-associated virus (AAV) neutralizing antibodies (NAbs) is essential for gene therapy success. Conventional cell-based transduction inhibition assays often encounter matrix-induced artifacts resulting from variable serum content across dilutions, which artificially inflate transduction baselines and mask partial neutralization. To address this challenge, we developed the constant serum concentration (CSC) assay, which maintains constant serum levels across dilutions to stabilize assay baselines and enhance NAb detection sensitivity. Using human sera across multiple AAV serotypes, we demonstrated that CSC reclassified up to 21.7% of samples classified as non-neutralizing by a conventional variable serum concentration (VSC) assay format. This improved sensitivity was validated using monoclonal antibody and multi-species serum test benchmarks and enhanced the reliability of seronegative control pool selection. Importantly, CSC detected persistent seropositivity in preclinical seroreversion models up to one year longer than a conventional VSC assay. Since even low-level neutralizing antibodies can significantly impact gene therapy efficacy, these findings have direct implications for optimizing AAV redosing strategies and refining patient stratification. By addressing fundamental limitations in NAb quantification while maintaining procedural simplicity, the CSC assay provides crucial insights into antibody persistence with translational relevance across species and clinical settings.

BackgroundThe hippocampus is one of the earliest brain regions affected in dementia‐related neurodegenerative diseases. While Alzheimer's disease (AD) has traditionally been regarded as the primary cause of hippocampal neuronal loss, other pathologies, such as limbic‐predominant age‐related TDP‐43 encephalopathy neuropathologic changes (LATE‐NC), also play a significant role. Age‐related lesions and the APOE ε4 allele, a major genetic risk factor for dementia, exhibit pathogenic synergy, further complicating the clinicopathological landscape.MethodWe analyzed 480 post‐mortem brains (ages 50–99) and used over 30,000 annotated neurons to train an algorithm for quantifying CA1 neuronal density across the cohort. Additional analyses included assessments of brain weight, cognitive status, and lesions such as Amyloid‐β (Aβ), phosphorylated tau, LATE‐NC, α‐synuclein, cerebral amyloid angiopathy (CAA), vascular lesions, Hirano bodies, and APOE genotyping.ResultsOur findings show that ADNC, LATE‐NC, amygdala‐predominant α‐synuclein, small vessel disease, and atherosclerosis contribute to CA1 neuronal degeneration, whereas Hirano bodies appear protective. Structural equation modeling highlighted a network of interconnected pathologies, with tau, LATE‐NC, and α‐synuclein emerging as primary drivers of hippocampal neuronal loss. Aβ deposits, capillary CAA, and LATE‐NC—but not phosphorylated tau—were directly influenced by APOE ε4.ConclusionHippocampal damage in age‐related dementias is multifactorial, extending beyond the contributions of Aβ and tau, with LATE‐NC playing a central role. APOE ε4 indirectly influences hippocampal degeneration by promoting Aβ‐related pathogenesis and triggering interactions among comorbid pathologies that drive neuronal loss.

Due to the growing use of high-dimensional data and methodological advances in medical research, reproducibility of research is increasingly dependent on the availability of reproducible code. However, code is rarely made available and too often only partly reproducible. Here, we aim to provide practical and easily implementable recommendations for medical researchers to improve the reproducibility of their code. We reviewed current coding practices in the population-based Rotterdam Study cohort. Based on this review, we formulated the following five recommendations to improve the reproducibility of code used in data analysis: (1) make reproducibility a priority and allocate time and resources; (2) implement systematic code review by peers, as it further strengthens reproducibility. We provide a code review checklist, which serves as a practical tool to facilitate structured code review; (3) write comprehensible code that is well-structured; (4) report decisions transparently, for instance by providing the annotated workflow code for data cleaning, formatting and sample selection; and (5) focus on accessibility of code and data and share both, when possible, via an open repository to foster accessibility. Ideally, this repository should be managed by the institution and should be accessible to everyone. Based on these five recommendations, medical researchers can take actionable steps to improve the reproducibility of their research. Importantly, these recommendations are thought to provide a practical starting point for enhancing reproducibility rather than mandatory guidelines.

Understanding the neural basis of social communication and vocal perception in primates is a key challenge in systems neuroscience. Vocalizations are fundamental for communication, and several cortical areas, known as "voice patches," have been identified as being sensitive to conspecific vocalizations in primates, vital for distinguishing species-specific calls. While the dorsal stream's role in complex auditory-motor functions and human speech processing is established, its specific contribution to processing species-specific vocalizations in non-human primates remains unclear. Using high-resolution fMRI (0.6 mm isotropic voxels), we investigated brain regions involved in processing vocalizations in awake rhesus monkeys exposed to coos, screams, and aggressive calls, among control sounds. Our analyses revealed a widespread network involved in vocalization processing, encompassing auditory-associated areas including the core and belt auditory cortices, as well as premotor, and somatosensory-related areas. Moreover, we found selective activation in the caudal part of the lateral sulcus (area Tpt) and the dorsal premotor cortex (area 6DR/F2) in response to vocalizations. Also, the population responses in these areas could discriminate between different vocalizations. Our results enhance our understanding of the neural basis of vocal communication in primates. Specifically, they highlight the involvement of a voice-related dorsal network in macaques, including Tpt and part of 6DR/F2, in processing the acoustic features of salient vocal stimuli, potentially linking them to motor representations. These findings provide insights into potential evolutionary precursors of auditory-motor pathways that support complex auditory communication systems in primates, including human speech.

Abstract Adeno-associated virus (AAV) gene therapy is often limited by pre-existing neutralizing antibodies (NAbs), yet current assays for NAb detection lack standardization and rarely quantify uncertainty, complicating cross-study comparisons. We present coreTIA (core Transduction Inhibition Assay), a modular experimental protocol combined with a statistically robust analysis pipeline that delivers precise, reproducible NAb titers with quantified uncertainty for every result. coreTIA’s statistical framework enables robust estimation of neutralization even when dilution series are incomplete, helping to reduce repeat testing and minimizing sample volume requirements. Evaluation and refinement of key assay parameters support consistent performance across AAV serotypes. By providing a protocol and analysis suite as an open resource, coreTIA facilitates more consistent and transparent NAb measurement, potentially aiding assay harmonization and regulatory assessment, addressing a key barrier to progress in gene therapy research and development.