Search Results (468)

Background/Objectives: This study aimed to examine the changes in brain metabolites and water molecule diffusion using chemical exchange saturation transfer (CEST) imaging and diffusion-weighted imaging (DWI) after 15 Gy of X-ray irradiation in a rat model of glioma. Methods: The glioma-derived cell line, C6, was implanted into the striatum of the right brain of 7-week-old male Wistar rats. CEST imaging and DWI were performed on days 8, 10, and 17 after implantation using a 7T-magnetic resonance imaging. X-ray irradiation (15 Gy) was performed on day 9. Magnetization transfer ratio (MTR) and apparent diffusion coefficient (ADC) values were calculated for CEST and DWI, respectively. Results: On day 17, the MTR values at 1.2 ppm, 1.5 ppm, 1.8 ppm, 2.1 ppm, and 2.4 ppm in the irradiated group decreased significantly compared with those of the control group. The standard deviation for the ADC values on a pixel-by-pixel basis increased from day 8 to day 17 (0.6 ± 0.06 → 0.8 ± 0.17 (×10⁻³ mm²/s)) in the control group, whereas it remained nearly unchanged (0.6 ± 0.06 → 0.8 ± 0.11 (×10⁻³ mm²/s)) in the irradiated group. Conclusions: This study revealed the effects of 15 Gy X-ray irradiation in a rat model of glioma using CEST imaging and DWI. Full article

The application of artificial intelligence through the brain–computer interface (BCI) is proving to be one of the great advances in neuroscience today. The development of surface electrodes over the cortex and very fine electrodes that can be stereotactically implanted in the brain have moved the science forward to the extent that paralyzed people can play chess and blind people can read letters. However, the introduction of foreign bodies into deeper parts of the central nervous system results in foreign body reaction, scarring, apoptosis, and decreased signaling. Implanted electrodes activate microglia, causing the release of inflammatory factors, the recruitment of systemic inflammatory cells to the site of injury, and ultimately glial scarring and the encapsulation of the electrode. Recordings historically fail between 6 months and 1 year; the longest BCI in use has been 7 years. This article proposes a biomolecular strategy provided by angiogenic cell precursors (ACPs) and nerve cell precursors (NCPs), administered intrathecally. This combination of cells is anticipated to sustain and promote learning across the BCI. Together, through the downstream activation of neurotrophic factors, they may exert a salutary immunomodulatory suppression of inflammation, anti-apoptosis, homeostasis, angiogenesis, differentiation, synaptogenesis, neuritogenesis, and learning-associated plasticity. Full article

Background/Objectives: Deep brain stimulation (DBS) is an effective surgical treatment for Parkinson’s Disease (PD) and other movement disorders. Despite its benefits, DBS explantation occurs in 5.6% of cases, with costs exceeding USD 22,000 per implant. Traditional statistical methods have struggled to identify reliable risk factors for explantation. We hypothesized that supervised machine learning would more effectively capture complex interactions among perioperative factors, enabling the identification of novel risk factors. Methods: The Medical Informatics Operating Room Vitals and Events Repository was queried for patients with DBS, adequate clinical data, and at least two years of follow-up (n = 38). Fisher’s exact test assessed demographic and medical history variables. Data were analyzed using Anaconda Version 2.3.1. with pandas, numpy, sklearn, sklearn-extra, matplotlin. pyplot, and seaborn. Recursive feature elimination with cross-validation (RFECV) optimized factor selection was used. A multivariate logistic regression model was trained and evaluated using precision, recall, F1-score, and area under the curve (AUC). Results: Fisher’s exact test identified chronic pain (p = 0.0108) and tobacco use (p = 0.0026) as risk factors. RFECV selected 24 optimal features. The logistic regression model demonstrated strong performance (precision: 0.89, recall: 0.86, F1-score: 0.86, AUC: 1.0). Significant risk factors included tobacco use (OR: 3.64; CI: 3.60–3.68), primary PD (OR: 2.01; CI: 1.99–2.02), ASA score (OR: 1.91; CI: 1.90–1.92), chronic pain (OR: 1.82; CI: 1.80–1.85), and diabetes (OR: 1.63; CI: 1.62–1.65). Conclusions: Our study suggests that supervised machine learning can identify risk factors for early DBS explantation. Larger studies are needed to validate our findings. Full article

Background/Objectives: Congenital cytomegalovirus (cCMV) infection is the most common non-genetic cause of sensorineural hearing loss (SNHL) in children. In cases of severe-to-profound SNHL, cochlear implantation (CI) is a widely used intervention, but outcomes remain variable due to possible neurodevelopmental comorbidities. This study aimed to evaluate the long-term auditory and language outcomes in children with cCMV after CI and to explore clinical and radiological predictors of post-CI performance. Methods: Fifty-three children with cCMV and bilateral severe-to-profound SNHL who underwent CI at five tertiary referral centers in Italy were included in the study. Auditory and language outcomes were assessed pre- and post-implantation using the Categories of Auditory Performance II (CAP-II) scale, the Nottingham 3-Level Classification, and the Bates Language Development Scale. Brain MRI abnormalities were classified according to the Alarcón classification. Correlations were explored between outcome scores and symptomatic status at birth, MRI findings, and neurodevelopmental comorbidities. Results: At birth, 40 children (75.5%) were symptomatic and 13 (24.5%) asymptomatic. Neurodevelopmental comorbidities were present in 19 children (35.8%). MRI was normal in 15 (28.3%), mildly abnormal in 26 (49%), and moderately to severely abnormal in 12 (22.6%). Auditory and language outcomes improved significantly post-CI (p < 0.001), though the outcomes varied widely. Twenty-five children (47%) reached CAP level ≥ 6, and thirteen (23%) reached Bates Level 6. Symptomatic status at birth correlated weakly with worse CAP (ρ = −0.291, p = 0.038) and Bates (ρ = −0.310, p = 0.028) scores. Higher Alarcón scores were significantly associated with neurodevelopmental comorbidities, though not directly with post-CI auditory and language outcomes. Finally, the presence of neurodevelopmental disabilities was generally associated with lower results, even if without statistical significance. Conclusions: CI provides substantial auditory and language benefit in children with cCMV, even in cases of severe neurodevelopmental comorbidities. MRI and developmental assessments, as well as perinatal history for clinical signs and symptoms, are helpful in guiding expectations and personalizing post-implantation support. Full article

Neurotrophins, such as brain-derived neurotrophic factor (BDNF) and neurosteroids, including allopregnanolone (ALLO), play critical roles in modulating neuronal activity in the brain. Levels of these compounds dynamically fluctuate in response to physiological and environmental conditions, particularly stress, suggesting complex regulatory interactions. This study aimed to explore the effects of acute stress and ALLO (individually and combined) on hippocampal expression of BDNF, its TrkB receptor, and other neurotrophins in sheep, a translational large animal model. Adult, luteal-phase sheep (n = 24), implanted with a guide cannula into the third brain ventricle, were divided into four experimental groups: (i) 3 days of Ringer–Locke solution (RL) infusion as the control; (ii) 3 days of RL infusion with 4 h acute stress on day three; (iii) 3 days of ALLO infusion (4 × 15 µg/60 µL/30 min) with 4 h acute stress on day three; and (iv) 3 days of ALLO infusion alone (n = 6 per group). Both acute stress and ALLO alone significantly reduced BDNF concentration and BDNF transcript abundance in the hippocampal CA1 and CA3 fields compared to the control group. The combined application of both stress and ALLO resulted in decreased levels of these parameters, except for BDNF concentration in the CA3 region. Additionally, TrkB mRNA expression in both hippocampal fields was significantly reduced in all treatment groups. Changes in mRNA levels for other neurotrophins, including nerve growth factor (NGF) and neurotrophin 3 (NT3) and 4 (NT4), varied under experimental conditions. While an inhibitory effect was predominant, NGF expression in the CA1 region remained unaffected by stress or ALLO. Interestingly, stress alone induced a significant increase in NT4 mRNA expression in the CA3 field compared to the control. In conclusion, the study demonstrated that a 4 h acute stress exposure inhibited the synthesis of BDNF, TrkB, and several other neurotrophins in the sheep hippocampus. Furthermore, ALLO, whose increased levels are highly correlated with the initial stress response, may serve as a mediator of this stress effect, temporarily preventing over-stimulation of hippocampal BDNF release and signaling. Full article

Objective: The aim of this study is to present the initiation of robotic-guided (RG) spine surgery into routine clinical care at a single center with the use of intraoperative CT (iCT) automatic registration-based navigation. The workflow included iCT with automatic registration, fusion with preoperative imaging, verification of preplanned screw trajectories, RG introduction of K-wires, and the insertion of pedicle screws (PSs), followed by a control iCT scan. Methods: All patients who underwent RG implantation of pedicle screws using the Cirq^® robotic arm (BrainLab, Munich, Germany) in the thoracolumbar spine at our department were included in the study. The accuracy of the pedicles screws was assessed using the Gertzbein–Robbins scale (GRS). Results: In total, 108 patients (60 female, mean age 68.7 ± 11.4 years) in 109 surgeries underwent RG PS placement. Indications included degenerative spinal disorders (n = 30 patients), spondylodiscitis (n = 24), tumor (n = 33), and fracture (n = 22), with a mean follow-up period of 7.7 ± 9 months. Thirty-seven cases (33.9%) were performed percutaneously, and all others were performed openly. Thirty-three operations were performed on the thoracic spine, forty-four on the lumbar and lumbosacral spine, thirty on the thoracolumbar, one on the cervicothoracic spine, and one on the thoracolumbosacral spine. The screws were inserted using a fluoroscopic (first 12 operations) or navigated technique (latter operations). The mean operation time was 228.8 ± 106 min, and the mean robotic time was 31.5 ± 18.4 min. The mean time per K-wire was 5.35 ± 3.98 min. The operation time was lower in the percutaneous group, while the robot time did not differ between the two groups. Robot time and the time per K-wire improved over time. Out of 688 screws, 592 were GRS A screws (86.1%), 54 B (7.8%), 22 C (3.2%), 12 D (1.7%), and 8 E (1.2%). Seven screws were revised intraoperatively, and after revision, all were GRS A. E screws were either revised or removed. In the case of D screws, screws located at the end of the construct were revised, while so-called in-out-in screws in the middle of the construct were not revised. Conclusions: Brainlab’s Cirq^® Robotic Alignment Module feature enables placement of pedicle screws in the thoracolumbar spine with high accuracy. A learning curve is shown through improvements in robotic time and time per K-wire. Full article

This study investigated the effects of lemon verbena extract (LVE) on sleep regulation using both a pentobarbital-induced sleep model and an EEG-based sleep assessment model in mice. To elucidate its potential mechanisms, mice were randomly assigned to five groups: control, positive control (diazepam, 2 mg/kg b.w.), and three LVE-treated groups receiving 40, 80, or 160 mg/kg b.w. via oral administration. In the pentobarbital-induced sleep model, mice underwent a two-week oral administration of LVE, followed by intraperitoneal pentobarbital injections. The results demonstrated that LVE significantly shortened sleep latency and prolonged sleep duration compared to the control group. Notably, adenosine A1 receptor expression, both at the mRNA and protein levels, was markedly upregulated in the brains of LVE-treated mice. Furthermore, LVE’s administration led to a significant increase in the mRNA expression of gamma-aminobutyric acid type A (GABA_A) receptor subunits (α2 and β2) in brain tissue. In the electroencephalography (EEG)/electromyogram (EMG)-based sleep model, mice underwent surgical implantation of EEG and EMG electrodes, followed by one week of LVE administration. Quantitative EEG analysis revealed that LVE treatment reduced wakefulness while significantly enhancing REM and NREM sleep’s duration, indicating its potential sleep-promoting effects. These findings suggest that LVE may serve as a promising natural sleep aid, improving both the quality and duration of sleep through the modulation of adenosine and GABAergic signaling pathways. Full article

Background/Objectives: Advancements in neuronavigation and intraoperative imaging have made gross-total resection of deep-seated lesions more feasible. However, in eloquently located regions, brain shift can lead to unintentional damage of functionally critical tissue during the approach. This study analyzes the feasibility and outcomes of a stereotactically guided microsurgical approach supported by intraoperative CT (iCT) for such lesions. Methods: Patients with deep-seated, eloquently located lesions treated between 03/2017 and 04/2023 at the Department of Neurosurgery, Ludwig-Maximilians-University (LMU) Munich, Germany, were included. Frame-based, image-guided stereotaxy was used for trajectory planning and catheter placement, verified by iCT. Microsurgical resection was conducted along the catheter trajectory using 2 mm conical blade retractors and continuous neurophysiological monitoring. Postoperative MRI assessed the extent of resection. Neurological outcomes were evaluated postoperatively, at 6 weeks, and at long-term follow-up in 12/2023. Results: A total of 12 patients were treated using the stereotactically guided microsurgical approach described in this study. In all cases, the implanted catheter precisely matched the preoperative trajectory, as confirmed by fused iCT data. Median durations were 23 min for stereotaxy and 3 h 7 min for microsurgery. Complete resection was achieved in all cases. One patient experienced transient hemiparesis and aphasia, both of which were fully resolved. All other patients showed neurological improvement or remained seizure-free at long-term follow-up. Conclusions: In selected cases, a stereotactically guided microsurgical approach with iCT enabled intraoperative localization of the target with high spatial accuracy and without immediate procedure-related complications in this limited cohort. Our findings support the feasibility of the technique; however, conclusions regarding clinical efficacy or broader applicability are limited by the small sample size and non-comparative study design. Full article

Epilepsy is a neurological disorder characterized by recurrent, unprovoked seizures, affecting millions worldwide. While anti-seizure medications serve as first-line treatment, approximately one-third of patients develop drug-resistant epilepsy (DRE), necessitating alternative interventions. Deep brain stimulation (DBS) has emerged as a promising therapy for DRE, particularly for patients who are ineligible for resective surgery. DBS involves stereotactic implantation of electrodes into target brain regions, such as the anterior nucleus of the thalamus (ANT), centromedian nucleus (CMT), and hippocampus (HC), to modulate aberrant neural activity and to reduce seizure frequency. Anesthesia plays a critical role in DBS implantation, influencing both patient safety and procedural success. The choice of anesthetic technique must balance patient comfort with the preservation of neurophysiological signals used for intraoperative electrode localization. A well-chosen anesthetic strategy can enhance the efficacy of electrode placement by minimizing patient movement and preserving critical neurophysiological signals for real-time monitoring. This precise targeting enhances safety via a reduction in perioperative risks and an improvement in long-term seizure control. Anesthetic considerations in epilepsy patients differ from those in movement disorders due to variations in their nuclei targets during DBS. Despite the increasing use of DBS for epilepsy following its FDA approval in 2018, research on anesthetic effects specific to this population remains limited. This narrative review, therefore, examines anesthetic approaches, pharmacological implications, potential complications, and evolving methods for DBS implantation in epilepsy patients, highlighting new insights and unique considerations in this population. Understanding these factors is essential for optimizing surgical outcomes and improving the safety and efficacy of DBS in epilepsy treatment. Full article

Background/Objectives: Intracranial macroelectrode implantation is a pivotal clinical tool in the evaluation of drug-resistant epilepsy, allowing further insights into the localization of the epileptogenic zone and the delineation of eloquent cortical regions through cortical stimulation. Additionally, it provides an avenue to study brain functions by analyzing cerebral responses during neuropsychological paradigms. By combining macroelectrodes with microelectrodes, which allow recording the activity of individual neurons or smaller neural clusters, recordings could provide deeper insights into neuronal microcircuits and the brain’s transitions in epilepsy and contribute to a better understanding of neuropsychological functions. In this study, one or two hybrid macro-micro electrodes were implanted in the anterior-inferior insular region in patients with refractory epilepsy. We report our experience and share some preliminary results; we also provide some recommendations regarding the implantation procedure for hybrid electrodes in the insular cortex. Methods: Stereoelectroencephalography was performed in 13 patients, with one or two hybrid macro-microelectrodes positioned in the insular region in each patient. Research neuropsychological paradigms could not be implemented in two patients for clinical reasons. In total, 23 hybrid macro-microelectrodes with eight microcontacts each were implanted, of which 20 were recorded. Spiking activity was detected and assessed using WaveClus3. Results: No spiking neural activity was detected in the microcontacts of the first seven patients. After iterative refinement during this process, successful recordings were obtained from 13 microcontacts in the anterior-inferior insula in the last four patients (13/64, 20.3%). Hybrid electrode implantation was uneventful with no complications. Obstacles included the absence of spiking activity signals, unsuccessful microwire dispersion, and the interference of environmental electrical noise in recordings. Conclusions: Human microelectrode recording presents a complex array of challenges; however, it holds the potential to facilitate a more comprehensive understanding of individual neuronal attributes and their specific stimulus responses. Full article

Objectives: This study aimed to develop a semi-automated registration method for aligning preoperative non-contrast T2-weighted MRI with postoperative high-resolution cone-beam CT (DynaCT) in patients undergoing directional deep brain stimulation (dDBS) surgery targeting the subthalamic nucleus (STN). The aim was to facilitate image-guided programming of DBS devices and postoperative verification of the alignment of segmented contacts. Materials and Methods: A dataset of ten patients undergoing bilateral dDBS implantation was retrospectively collected, including DynaCT (acquired postoperatively) and non-contrast T2-weighted MRI (obtained preoperatively). A semi-automated registration method was used, employing manual initialization due to dissimilar anatomical information between DynaCT and T2-weighted MRI. Image visualization, initial alignment using a centered transformation initializer, and single-resolution image registration involving the Simple Insight Toolkit (SimpleITK) library were performed. Manual landmark-based alignment based on anatomical landmarks and evaluation metrics such as Target Registration Error (TRE) assessed alignment accuracy. Results: The registration method successfully aligned all images. Quantitative evaluation revealed an average of the mean TRE of 1.48 mm across all subjects, indicating satisfactory alignment quality. Multiplanar reformations (MPRs) based on electrode-oriented normal vectors visualized segmented contacts for accurate electrode placement. Conclusions: The developed method demonstrated successful registration between preoperative non-contrast T2-weighted MRI and postoperative DynaCT, despite dissimilar anatomical information. This approach facilitates accurate alignment crucial for DBS programming and postoperative verification, potentially reducing the programming time of the DBS. The study underscores the importance of image quality, manual initialization and semi-automated registration methods for successful multimodal image registration in dDBS procedures targeting the STN. Full article

Lung cancer brain metastasis (LCBM) is a major contributor to cancer-related mortality, with a median survival of 8–16 months following diagnosis, despite advances in therapeutic strategies. The development of clinically relevant animal models is crucial for understanding the metastatic cascade and assessing therapies that can penetrate the blood–brain barrier (BBB). This review critically evaluates five primary LCBM modeling approaches—orthotopic implantation, intracardiac injection, stereotactic intracranial injection, carotid artery injection, and tail vein injection—focusing on their clinical applicability. We systematically compare their ability to replicate human metastatic pathophysiology and highlight emerging technologies for personalized therapy screening. Additionally, we analyze breakthrough strategies in central nervous system (CNS)-targeted drug delivery, including microparticle targeted delivery systems designed to enhance brain accumulation. By incorporating advances in single-cell omics and AI-driven metastasis prediction, this work provides a roadmap for the next generation of LCBM models, aimed at bridging preclinical and clinical research. Full article

Brain-inspired models in artificial intelligence (AI) originated from foundational insights in neuroscience. In recent years, this relationship has been moving toward a mutually reinforcing feedback loop. Currently, AI is significantly contributing to advancing our understanding of neuroscience. In particular, when combined with wireless optogenetics, AI enables experiments without physical constraints. Furthermore, AI-driven real-time analysis facilitates closed-loop control, allowing experimental setups across a diverse range of scenarios. And a deeper understanding of these neural networks may, in turn, contribute to future advances in AI. This work demonstrates the synergy between AI and miniaturized neural technology, particularly through wireless optogenetic systems designed for closed-loop neural control. We highlight how AI is now revolutionizing neuroscience experiments from decoding complex neural signals and quantifying behavior, to enabling closed-loop interventions and high-throughput phenotyping in freely moving subjects. Notably, AI-integrated wireless implants can monitor and modulate biological processes with unprecedented precision. We then recount how neuroscience insights derived from AI-integrated neuroscience experiments can potentially inspire the next generation of machine intelligence. Insights gained from these technologies loop back to inspire more efficient and robust AI systems. We discuss future directions in this positive feedback loop between AI and neuroscience, arguing that the coevolution of the two fields, grounded in technologies like wireless optogenetics and guided by reciprocal insight, will accelerate progress in both, while raising new challenges and opportunities for interdisciplinary collaboration. Full article

Background: Glucagon-like peptide-2 (GLP-2) is a gut hormone secreted in response to nutrient intake and regulates lipid metabolism in the gut. The present study aims to elucidate the underlying mechanism of GLP-2 in stimulating gut lipid secretion in the fasted state by testing whether GLP-2 signals through the brain’s GLP-2 receptor and melanocortin 4 receptor (MC4R). Methods: Sprague-Dawley rats were implanted with a mesenteric lymph duct cannula for measuring gut lipid secretion and an intracerebroventricular cannula for infusion of a GLP-2R antagonist (GLP-2(11-33)), an MC4R antagonist (SHU9119), or saline as a control. The rat received a lipid infusion into the small intestine and a peritoneal injection of GLP-2 five hours later. Results: Brain administration of a GLP-2R antagonist or an MC4R antagonist attenuated the stimulatory effects of peripheral GLP-2 on lymph triglyceride output. These effects were associated with differential changes in the expression of key genes in jejunal endothelial cells, smooth muscle cells, and neuronal cells. Conclusions: These results support the involvement of central GLP-2R and MC4R in a neural pathway for GLP-2 to mobilize lipids stored in the gut during the post-absorptive state. Full article

An implantable multi-ion image sensor equipped with magnesium ion (Mg²⁺)-and calcium ion (Ca²⁺)-sensitive membranes was fabricated for the selective measurement of extracellular Mg²⁺ in the brain, and the sensor performance was evaluated. This sensor complements the low selectivity of the Mg²⁺-sensitive membrane for Ca²⁺ by depositing a Ca²⁺-sensitive membrane in addition to the Mg²⁺-sensitive membrane on a CMOS (Complementary Metal Oxide Semiconductor)-based potentiometric sensor array with 5.65 × 4.39 µm² pitch, enabling selective measurement of Mg²⁺ and Ca²⁺. Characterization of the sensor confirmed a Ca²⁺ sensitivity of 26.5 mV/dec and Mg²⁺ sensitivity of 19 mV/dec. Based on validation experiments with varying concentrations of Mg²⁺ and Ca²⁺, selective Ca²⁺ and Mg²⁺ measurements were successfully achieved. Furthermore, real-time imaging of Mg²⁺ and Ca²⁺ and quantification of their concentration changes were performed. The developed sensor may be successfully applied for extracellular multi-ion imaging of Mg²⁺ and Ca²⁺ in the living brain. Full article