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Background and Objectives: The surgical resection of insular gliomas is associated with a high rate of postoperative morbidity as they grow close to descending motor fibers and lenticulostriate arteries. It is believed that intraoperative perforator infarctions are the determining factor for patients' postoperative outcome, while the majority of patients with intraoperative ischemic events do not develop postoperative motor deficits. This study aims to evaluate whether navigated transcranial magnetic stimulation (nTMS) and nTMS-based fiber tracking could be valuable for the preoperative assessment of patients with insular gliomas., Methods: Thirty-two patients with insular gliomas were presurgically examined by nTMS. The resting motor threshold and cortical representation areas of legs, hands, and face were identified on both hemispheres. Motor evoked potential positive stimulation points were then used as a region of interest for diffusion tensor imaging tractographies. Somatotopic fiber tracking was performed enabling analyses of the spatial relation between tumor and cortico-spinal tract (CST) as well as the extraction of fiber tract integrity, measured by fractional anisotropy and the apparent diffusion coefficient., Results: The performance of nTMS mappings of the motor cortex and reconstruction of descending motor fibers for legs, hands, and facial functioning was successful in all patients. Higher preoperative resting motor threshold ratios and a distance between tumor and CST of <3 mm were associated with a permanent deterioration in motor function (P = .029 and P = .007). Shorter distances between CST and tumorous tissue were correlated with lowered peritumoral fractional anisotropy values, suggesting alterations in fiber tract integrity. Lower interhemispheric peritumoral fractional anisotropy ratios showed an association with new postoperative motor deficits (P = .017)., Conclusion: nTMS-based diffusion tensor imaging tractography enables somatotopic tract visualization and provides a valuable tool for preoperative planning, intraoperative orientation, and individual risk stratification. Thus, it may be beneficial to increase safety in insular glioma resection surgery., (Copyright © Congress of Neurological Surgeons 2024. All rights reserved.)

Background: Subjective reports can reveal relevant information regarding the nature of the impairment of brain tumor patients, unveiling potential gaps in current assessment practices. The co-occurrence of language and memory impairments has been previously reported, albeit scarcely. The aim of this study is therefore to understand the co-occurrence of subjective language and memory complaints in the preoperative state of brain tumor patients and its impact on Quality of Life (QoL)., Methods: 31 brain tumor patients (12 LGG, 19 HGG) underwent a semi-structured interview to assess subjective complaints of language deficits, co-occurrences between language and memory dysfunction, and changes in QoL. Group and subgroup analyses were conducted to provide general and tumor grade specific data., Results: 48.4% of patients mentioned co-occurrence of language and memory impairments in reading, writing, and conversation. The HGG group reported co-occurrences in all three of these (reading: 31.6%; writing: 21.1%; conversation: 26.3%), while the LGG only described co-occurrences in reading (25%) and conversation (8.3%), although these were not statistically significant. All patients with co-occurring language and memory deficits reported these to be linked to reduced QoL (48.4%). In patients with an HGG, this number was slightly higher (52.6%) than in patients with an LGG (41.7%)., Conclusion: Language impairments co-occur with memory dysfunction as perceived in patients' daily life. Patients see these impairments as affecting their quality of life. Further attention to dedicated language and memory tasks seems necessary., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Rybka, Jonkers, Burzlaff, Rosenstock, Vajkoczy, Picht, Faust and Rofes.)

Background: One of the challenges in surgery of tumors in motor eloquent areas is the individual risk assessment for postoperative motor disorder. Previously a regression model was developed that permits estimation of the risk prior to surgery based on topographical and neurophysiological data derived from investigation with nTMS (navigated Transcranial Magnetic Stimulation). This study aims to analyze the impact of including additional neurophysiological TMS parameters into the established risk stratification model for motor outcome after brain tumor surgery., Methods: Biometric and clinical data of 170 patients with glioma in motor eloquent areas were collected prospectively. In addition, the following nTMS parameters were collected bihemispherically prior to surgery: resting motor threshold (RMT), recruitment curve (RC), cortical silent period (CSP) and a nTMS based fibertracking to measure the tumor tract distance (TTD). Motor function was quantified by Medical Research Council Scale (MRCS) preoperatively, seven days and three months postoperatively. Association between nTMS parameters and postoperative motor outcome was investigated in bivariate and multivariable analyses., Results: The bivariate analysis confirmed the association of RMT ratio with the postoperative motor outcome after seven days with higher rates of worsening in patients with RMT ratio > 1.1 compared to patients with RMT ratio ≤ 1.1 (31.6% vs. 15.1%, p = 0.009). Similarly, an association between a pathological CSP ratio and a higher risk of new postoperative motor deficits after seven days was observed (35.3% vs. 16.7% worsening, p = 0.025). A pathological RC Ratio was associated postoperative deterioration of motor function after three months (42.9% vs. 16.2% worsening, p = 0.004). In multiple regression analysis, none of these associations were statistically robust., Conclusions: The current results suggest that the RC ratio, CSP ratio and RMT ratio individually are sensitive markers associated with the motor outcome 7 days and 3 months after tumor resection in a presumed motor eloquent location. They can therefore supply valuable information during preoperative risk-benefit-balancing. However, underlying neurophysiological mechanisms might be too similar to make the parameters meaningful in a combined model., (© 2024. The Author(s).)

Digital twins enable simulation, comprehensive analysis and predictions, as virtual representations of physical systems. They are also finding increasing interest and application in the healthcare sector, with a particular focus on digital twins of the brain. We discuss how digital twins in neuroscience enable the modeling of brain functions and pathology as they offer an in-silico approach to studying the brain and illustrating the complex relationships between brain network dynamics and related functions. To showcase the capabilities of digital twinning in neuroscience we demonstrate how the impact of brain tumors on the brain's physical structures and functioning can be modeled in relation to the philosophical concept of plasticity. Against this technically derived backdrop, which assumes that the brain's nonlinear behavior toward improvement and repair can be modeled and predicted based on MRI data, we further explore the philosophical insights of Catherine Malabou. Malabou emphasizes the brain's dual capacity for adaptive and destructive plasticity. We will discuss in how far Malabou's ideas provide a more holistic theoretical framework for understanding how digital twins can model the brain's response to injury and pathology, embracing Malabou's concept of both adaptive and destructive plasticity which provides a framework to address such yet incomputable aspects of neuroscience and the sometimes seemingly unfavorable dynamics of neuroplasticity helping to bridge the gap between theoretical research and clinical practice., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Fekonja, Schenk, Schröder, Tomasello, Tomšič and Picht.)

Navigated Transcranial Magnetic Stimulation (nTMS) is commonly used to causally identify cortical regions involved in language processing. Combining tractography with nTMS has been shown to increase induced error rates by targeting stimulation of cortical terminations of white matter fibers. According to functional Magnetic Resonance Imaging (fMRI) data, bilateral cortical areas connected by the arcuate fasciculus (AF) have been implicated in the processing of transitive compared to unergative verbs. To test this connection between transitivity and bilateral perisylvian regions, we administered a tractography-based inhibitory nTMS protocol during action naming of finite transitive (The man reads) and unergative (The man sails) verbs. After tracking the left and right AF, we stimulated the cortical terminations of the tract in frontal, parietal and temporal regions in 20 neurologically healthy native speakers of German. Results revealed that nTMS induced more errors during transitive compared to unergative verb naming when stimulating the left (vs right) AF terminations. This effect was specific to the left temporal terminations of the AF, whereas no differences between the two verb types were identified when stimulating inferior parietal and frontal AF terminations. Induced errors for transitive verbs over left temporal terminations mostly manifested as access errors (i.e., hesitations). Given the inhibitory nature of our nTMS protocol, these results suggest that temporal regions of the left hemisphere play a crucial role in argument structure processing. Our findings align with previous data on the role of left posterior temporal regions in language processing and by providing further evidence from a language production experiment using tractography-based inhibitory nTMS., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The field of medicine is quickly evolving and becoming increasingly more multidisciplinary and technologically demanding. Medical education, however, does not yet adequately reflect these developments and new challenges, which calls for a reform in the way aspiring medical professionals are taught and prepared for the workplace. The present article presents an attempt to address this shortcoming in the form of a newly conceptualized course for medical students with a focus on the current demands and trends in modern neurosurgery. Competency-based education is introduced as a conceptual framework comprising academic and operational competence as well as life-world becoming. This framework provides a sound educational foundation for future medical professionals, equipping them with the knowledge as well as skills needed to successfully navigate the medical field in the current day and age. Three competencies are identified that are central to day-to-day medical practice, namely digitalization, multidisciplinarity, and the impact of recent developments on the changing patient-practitioner relationship. These competencies are relevant for all medical disciplines, but are demonstrated here in a neurosurgical context and visualized using a real patient's case study. Students follow this sample patient's way through each step of the neurosurgical workflow, from planning to performing the procedure, and can see for themselves the importance and application of the aforementioned competencies based on this real-world example. Courses such as the one presented here may prepare medical students more adequately for their future work by combining theoretical and practical skills and critical reflection, thereby providing holistic and practical insights as well as a conceptual framework for their future careers., Competing Interests: The authors declare no relevant financial or non-financial conflicts of interest with respect to the authorship and/or publication of this article., (© 2024 Picht et al.)

Objective: This prospective study assesses the acceptance and usefulness of augmented 360° virtual reality (VR) videos for early student education and preparation in the field of neurosurgery., Methods: Thirty-five third-year medical students participated. Augmented 360° VR videos depicting three neurosurgical procedures (lumbar discectomy, brain metastasis resection, clipping of an aneurysm) were presented during elective seminars. Multiple questionnaires were employed to evaluate conceptual and technical aspects of the videos. The analysis utilized ordinal logistic regression to identify crucial factors contributing to the learning experience of the videos., Results: The videos were consistently rated as good to very good in quality, providing detailed demonstrations of intraoperative anatomy and surgical workflow. Students found the videos highly useful for their learning and preparation for surgical placements, and they strongly supported the establishment of a VR lounge for additional self-directed learning. Notably, 81% reported an increased interest in neurosurgery, and 47% acknowledged the potential influence of the videos on their future choice of specialization. Factors associated with a positive impact on students' interest and learning experience included high technical quality and comprehensive explanations of the surgical steps., Conclusions: This study demonstrated the high acceptance of augmented 360° VR videos as a valuable tool for early student education in neurosurgery. While hands-on training remains indispensable, these videos promote conceptual knowledge, ignite interest in neurosurgery, and provide a much-needed orientation within the operating room. The incorporation of detailed explanations throughout the surgeries with augmentation using superimposed elements, offers distinct advantages over simply observing live surgeries., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objective: Surgical resection of motor eloquent tumors poses the risk of causing postoperative motor deficits which leads to reduced quality of life in these patients. Currently, rehabilitative procedures are limited with physical therapy being the main treatment option. This study investigated the efficacy of repetitive navigated transcranial magnetic stimulation (rTMS) for treatment of motor deficits after supratentorial tumor resection., Methods: This randomized, double-blind, sham-controlled trial (DRKS00010043) recruited patients with a postoperatively worsened upper extremity motor function immediately postoperatively. They were randomly assigned to receive rTMS (1Hz, 110% RMT, 15 minutes, 7 days) or sham stimulation to the motor cortex contralateral to the injury followed by physical therapy. Motor and neurological function as well as quality of life were assessed directly after the intervention, one month and three months postoperatively., Results: Thirty patients were recruited for this study. There was no significant difference between both groups in the primary outcome, the Fugl Meyer score three months postoperatively [Group difference (95%-CI): 5.05 (-16.0; 26.1); p=0.631]. Patients in the rTMS group presented with better hand motor function one month postoperatively. Additionally, a subgroup of patients with motor eloquent ischemia showed lower NIHSS scores at all timepoints., Conclusions: Low-frequency rTMS facilitated the recovery process in stimulated hand muscles, but with limited generalization to other functional deficits. Long-term motor deficits were not impacted by rTMS. Given the reduced life expectancy in these patients a shortened recovery duration of deficits can still be of high significance., Clinical Trial Registration: https://drks.de/DRKS00010043., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Engelhardt, Schneider, Reuther, Grittner, Vajkoczy, Picht and Rosenstock.)

Objective: Language dominance in the developing brain can vary widely across anatomical and pathological conditions as well as age groups. Repetitive navigated transcranial magnetic stimulation (rnTMS) has been applied to calculate the hemispheric dominance ratio (HDR) in adults. In this study, the authors aimed to assess the feasibility of using rnTMS to identify language lateralization in a pediatric neurosurgical cohort and to correlate the preoperative rnTMS findings with the postoperative language outcome., Methods: A consecutive prospectively collected cohort of 19 children with language-associated lesions underwent bihemispheric rnTMS mapping prior to surgery (100 stimulation sites on each hemisphere). In addition to feasibility and adverse effects, the HDR (ratio of the left hemisphere to right hemisphere error rate) was calculated. The anatomical surgical site and postoperative language outcome at 3 months after surgery were assessed according to clinical documentation., Results: Repetitive nTMS mapping was feasible in all 19 children (mean age 12.5 years, range 4-17 years; 16 left-sided lesions) without any relevant adverse events. Thirteen children (68%) showed left hemispheric dominance (HDR > 1.1), and 2 children (11%) showed right hemispheric dominance (HDR < 0.9). In 4 children (21%), the bihemispheric error rates were nearly the same (HDR ≥ 0.9 and ≤ 1.1). Sixteen children underwent surgery (14 tumor/lesion resections and 2 hemispherotomies) and 3 patients continued conservative therapy. After surgery, 4 patients (25%) showed an improvement in language function, 10 (63%) presented with stable language function, and 2 (12.5%) experienced deterioration in language function. Of the 6 patients with right hemispheric language involvement, 4 (80%) had glial tumors, 1 (20%) had focal cortical dysplasia, and 1 (20%) experienced hypoxic brain injury. Children with right hemispheric language involvement (HDR ≤ 1.1) did not show any language deterioration postoperatively., Conclusions: Bihemispheric rnTMS language mapping as a noninvasive mapping technique to assess lateralization of language function in the pediatric neurosurgical population is safe and feasible. Why relevant right hemispheric language function (HDR ≤ 1.1) was associated with postoperative unaltered language function needs to be validated in future studies. Bihemispheric rnTMS language mapping strengthens risk-benefit considerations prior to pediatric tumor/epilepsy surgery in language-associated areas.

Introduction: Surgery on the brainstem level is associated with a high-risk of postoperative morbidity. Recently, we have introduced the combination of navigated transcranial magnetic stimulation (nTMS) and diffusion tensor imaging (DTI) tractography to define functionally relevant motor fibers tracts on the brainstem level to support operative planning and risk stratification in brainstem cavernomas., Research Question: Evaluate this method and assess it's clinical impact for the surgery of brainstem gliomas., Material and Methods: Patients with brainstem gliomas were examined preoperatively with motor nTMS and DTI tractography. A fractional anisotropy (FA) value of 75% of the individual FA threshold (FAT) was used to track descending corticospinal (CST) and -bulbar tracts (CBT). The distance between the tumor and the somatotopic tracts (hand, leg, face) was measured and diffusion parameters were correlated to the patients' outcome., Results: 12 patients were enrolled in this study, of which 6 underwent surgical resection, 5 received a stereotactic biopsy and 1 patient received conservative treatment. In all patients nTMS mapping and somatotopic tractography were performed successfully. Low FA values correlated with clinical symptoms revealing tract alteration by the tumor (p = 0.049). A tumor-tract distance (TTD) above 2 mm was the critical limit to achieve a safe complete tumor resection., Discussion and Conclusion: nTMS based DTI tractography combined with local diffusion analysis is a valuable tool for preoperative visualization and functional assessment of relevant motor fiber tracts, improving planning of safe entry corridors and perioperative risk stratification in brainstem gliomas tumors. This technique allows for customized treatment strategy to maximize patients' safety., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. T. Picht has served as a speaker for Nexstim Oy but is not a contracted consultant., (© 2024 The Authors.)

Importance: The prognosis of overall survival (OS) in patients with glioblastoma (GBM) may depend on the underlying structural connectivity of the brain., Objective: To examine the association between white matter tracts affected by GBM and patients' OS by means of a new tract density index (TDI)., Design, Setting, and Participants: This prognostic study in patients with a histopathologic diagnosis of GBM examined a discovery cohort of 112 patients who underwent surgery between February 1, 2015, and November 30, 2020 (follow-up to May 31, 2023), in Italy and 70 patients in a replicative cohort (n = 70) who underwent surgery between September 1, 2012, and November 30, 2015 (follow-up to May 31, 2023), in Germany. Statistical analyses were performed from June 1, 2021, to May 31, 2023. Thirteen and 12 patients were excluded from the discovery and the replicative sets, respectively, because of magnetic resonance imaging artifacts., Exposure: The density of white matter tracts encompassing GBM., Main Outcomes and Measures: Correlation, linear regression, Cox proportional hazards regression, Kaplan-Meier, and prediction analysis were used to assess the association between the TDI and OS. Results were compared with common prognostic factors of GBM, including age, performance status, O6-methylguanine-DNA methyltransferase methylation, and extent of surgery., Results: In the discovery cohort (n = 99; mean [SD] age, 62.2 [11.5] years; 29 female [29.3%]; 70 male [70.7%]), the TDI was significantly correlated with OS (r = -0.34; P < .001). This association was more stable compared with other prognostic factors. The TDI showed a significant regression pattern (Cox: hazard ratio, 0.28 [95% CI, 0.02-0.55; P = .04]; linear: t = -2.366; P = .02). and a significant Kaplan-Meier stratification of patients as having lower or higher OS based on the TDI (log-rank test = 4.52; P = .03). Results were confirmed in the replicative cohort (n = 58; mean [SD] age, 58.5 [11.1] years, 14 female [24.1%]; 44 male [75.9%]). High (24-month cutoff) and low (18-month cutoff) OS was predicted based on the TDI computed in the discovery cohort (accuracy = 87%)., Conclusions and Relevance: In this study, GBMs encompassing regions with low white matter tract density were associated with longer OS. These findings indicate that the TDI is a reliable presurgical outcome predictor that may be considered in clinical trials and clinical practice. These findings support a framework in which the outcome of GBM depends on the patient's brain organization.

Background: The extent of resection of glioma is one of the most important predictors of the survival duration of patients after surgery. The presence of eloquent areas within or near a tumor often limits resection, as resection of these areas would result in functional loss and reduced quality of life. The aim of this randomized, triple-blind, sham-controlled study is to investigate the capability of repetitive navigated transcranial magnetic stimulation (rnTMS) over the primary motor cortex to facilitate the functional reorganization of the motor network., Methods: One hundred forty-eight patients with tumors in movement-relevant areas will be included in this randomized, sham-controlled, bicentric, triple-blind clinical trial. Patients considered at high risk for postoperative motor deficits according to an initial nTMS assessment will receive inhibitory rnTMS at 1 Hz for 30 min followed by a short motor training of 10 min. Stimulation will be applied to the fiber endings of the corticospinal tract closest to the tumor based on individualized tractography. Stimulation will be performed twice daily for each 30 min for 5-28 days depending on the individually available time between study inclusion and surgery. The intervention is controlled by a sham stimulation group (1:1 randomization), where a plastic adapter will be placed on the coil. We expect a comparable or better motor status 3 months postoperatively as measured by the British Medical Research Council (BMRC) score for the affected upper extremity (non-inferiority) and a higher rate of gross total resections (superiority) in the rnTMS compared to the sham group., Discussion: The generated reorganization of the brain's areas for motor function should allow a more extensive and safer removal of the tumor while preserving neurological and motor function. This would improve both survival and quality of life of our patients., Trial Registration: DRKS.de DRKS00017232 . Registered on 28 January 2020., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: The supplementary motor area (SMA) is important for motor and language function. Damage to the SMA may harm these functions, yet tools for a preoperative assessment of the area are still sparse., Objective: The aim of this study was to validate a mapping protocol using repetitive navigated transcranial magnetic stimulation (rnTMS) and extend this protocol for both hemispheres and lower extremities., Methods: To this purpose, the SMA of both hemispheres were mapped based on a finger tapping task for 30 healthy subjects (35.97 ± 15.11, range 21-67 years; 14 females) using rnTMS at 20 Hz (120% resting motor threshold (RMT)) while controlling for primary motor cortex activation. Points with induced errors were marked on the corresponding MRI. Next, on the identified SMA hotspot a bimanual finger tapping task and the Nine-Hole Peg Test (NHPT) were performed. Further, the lower extremity was mapped at 20 Hz (140%RMT) using a toe tapping task., Results: Mean finger tapping scores decreased significantly during stimulation (25.70taps) compared to baseline (30.48; p  < 0.01). Bimanual finger tapping led to a significant increase in taps during stimulation (28.43taps) compared to unimanual tapping ( p  < 0.01). Compared to baseline, completion time for the NHPT increased significantly during stimulation (baseline: 13.6 s, stimulation: 16.4 s; p  < 0.01). No differences between hemispheres were observed., Conclusion: The current study validated and extended a rnTMS based protocol for the mapping of the SMA regarding motor function of upper and lower extremity. This protocol could be beneficial to better understand functional SMA organisation and improve preoperative planning in patients with SMA lesions., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Kern, Kempter, Picht and Engelhardt.)

White matter impairments caused by gliomas can lead to functional disorders. In this study, we predicted aphasia in patients with gliomas infiltrating the language network using machine learning methods. We included 78 patients with left-hemispheric perisylvian gliomas. Aphasia was graded preoperatively using the Aachen aphasia test (AAT). Subsequently, we created bundle segmentations based on automatically generated tract orientation mappings using TractSeg. To prepare the input for the support vector machine (SVM), we first preselected aphasia-related fiber bundles based on the associations between relative tract volumes and AAT subtests. In addition, diffusion magnetic resonance imaging (dMRI)-based metrics [axial diffusivity (AD), apparent diffusion coefficient (ADC), fractional anisotropy (FA), and radial diffusivity (RD)] were extracted within the fiber bundles' masks with their mean, standard deviation, kurtosis, and skewness values. Our model consisted of random forest-based feature selection followed by an SVM. The best model performance achieved 81% accuracy (specificity = 85%, sensitivity = 73%, and AUC = 85%) using dMRI-based features, demographics, tumor WHO grade, tumor location, and relative tract volumes. The most effective features resulted from the arcuate fasciculus (AF), middle longitudinal fasciculus (MLF), and inferior fronto-occipital fasciculus (IFOF). The most effective dMRI-based metrics were FA, ADC, and AD. We achieved a prediction of aphasia using dMRI-based features and demonstrated that AF, IFOF, and MLF were the most important fiber bundles for predicting aphasia in this cohort., (© 2023 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)

Background: Damage to the supplementary motor area (SMA) can lead to impairments of motor and language function. A detailed preoperative mapping of functional boarders of the SMA could therefore aid preoperative diagnostics in these patients., Objective: The aim of this study was the development of a repetitive nTMS protocol for non-invasive functional mapping of the SMA while assuring effects are caused by SMA rather than M1 activation., Methods: The SMA in the dominant hemisphere of 12 healthy subjects (28.2 ± 7.7 years, 6 females) was mapped using repetitive nTMS at 20 Hz (120% RMT), while subjects performed a finger tapping task. Reductions in finger taps were classified in three error categories (≤15% = no errors, 15-30% = mild, >30% significant). The location and category of induced errors was marked in each subject's individual MRI. Effects of SMA stimulation were then directly compared to effects of M1 stimulation in four different tasks (finger tapping, writing, line tracing, targeting circles)., Results: Mapping of the SMA was possible for all subjects, yet effect sizes varied. Stimulation of the SMA led to a significant reduction of finger taps compared to baseline (BL: 45taps, SMA: 35.5taps; p  < 0.01). Line tracing, writing and targeting of circles was less accurate during SMA compared to M1 stimulation., Conclusion: Mapping of the SMA using repetitive nTMS is feasible. While errors induced in the SMA are not entirely independent of M1, disruption of the SMA induces functionally distinct errors. These error maps can aid preoperative diagnostics in patients with SMA related lesions., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Engelhardt, Kern, Karhu and Picht.)

People with tumours in specific brain sites might face difficulties in tasks with different linguistic material. Previous lesion-symptom mapping studies (VLSM) demonstrated that people with tumours in posterior temporal regions have more severe linguistic impairments. However, to the best of our knowledge, preoperative performance and lesion location on tasks with different linguistic stimuli have not been examined. In the present study, we performed VLSM on 52 people with left gliomas to examine whether tumour distribution differs depending on the tasks of the Aachen Aphasia Test. The VLSM analysis revealed that single-word production (e.g. object naming) was associated with the inferior parietal lobe and that compound and sentence production were additionally associated with posterior temporal gyri. Word repetition was affected in people with tumours in inferior parietal areas, whereas sentence repetition was the only task to be associated with frontal regions. Subcortically, word and sentence production were found to be affected in people with tumours reaching the arcuate fasciculus, and compound production was primarily associated with tumours affecting the inferior longitudinal and inferior fronto-occipital fasciculus. Our work shows that tasks with linguistic stimuli other than single-word naming (e.g. compound and sentence production) relate to additional cortical and subcortical brain areas. At a clinical level, we show that tasks that target the same processes (e.g. repetition) can have different neural correlates depending on the linguistic stimuli used. Also, we highlight the importance of left temporoparietal areas., (© 2023 The Authors. Journal of Neuropsychology published by John Wiley & Sons Ltd on behalf of The British Psychological Society.)

The review provides a comprehensive update (previous report: Chen R, Cros D, Curra A, Di Lazzaro V, Lefaucheur JP, Magistris MR, et al. The clinical diagnostic utility of transcranial magnetic stimulation: report of an IFCN committee. Clin Neurophysiol 2008;119(3):504-32) on clinical diagnostic utility of transcranial magnetic stimulation (TMS) in neurological diseases. Most TMS measures rely on stimulation of motor cortex and recording of motor evoked potentials. Paired-pulse TMS techniques, incorporating conventional amplitude-based and threshold tracking, have established clinical utility in neurodegenerative, movement, episodic (epilepsy, migraines), chronic pain and functional diseases. Cortical hyperexcitability has emerged as a diagnostic aid in amyotrophic lateral sclerosis. Single-pulse TMS measures are of utility in stroke, and myelopathy even in the absence of radiological changes. Short-latency afferent inhibition, related to central cholinergic transmission, is reduced in Alzheimer's disease. The triple stimulation technique (TST) may enhance diagnostic utility of conventional TMS measures to detect upper motor neuron involvement. The recording of motor evoked potentials can be used to perform functional mapping of the motor cortex or in preoperative assessment of eloquent brain regions before surgical resection of brain tumors. TMS exhibits utility in assessing lumbosacral/cervical nerve root function, especially in demyelinating neuropathies, and may be of utility in localizing the site of facial nerve palsies. TMS measures also have high sensitivity in detecting subclinical corticospinal lesions in multiple sclerosis. Abnormalities in central motor conduction time or TST correlate with motor impairment and disability in MS. Cerebellar stimulation may detect lesions in the cerebellum or cerebello-dentato-thalamo-motor cortical pathways. Combining TMS with electroencephalography, provides a novel method to measure parameters altered in neurological disorders, including cortical excitability, effective connectivity, and response complexity., (Copyright © 2023 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

Transcranial magnetic stimulation (TMS) has provided relevant evidence regarding the neural correlates of language. The aim of the present study is to summarize and assess previous findings regarding linguistic levels (i.e., semantic and morpho-syntactic) and brain structures utilized during verb and sentence processing. To do that, we systematically reviewed TMS research on verb and sentence processing in healthy speakers, and meta-analyzed TMS-induced effects according to the region of stimulation and experimental manipulation. Findings from 45 articles show that approximately half of the reviewed work focuses on the embodiment of action verbs. The majority of studies (60%) target only one cortical region in relation to a specific linguistic process. Frontal areas are most frequently stimulated in connection to morphosyntactic processes and action verb semantics, and temporoparietal regions in relation to integration of sentential meaning and thematic role assignment. A meta-analysis of 72 effect sizes of the reviewed papers indicates that TMS has a small overall effect size, but effect sizes for anterior compared to posterior regions do not differ for semantic or morphosyntactic contrasts. Our findings stress the need to increase the number of targeted areas, while using the same linguistic contrasts in order to disentangle the contributions of different cortical regions to distinct linguistic processes., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Informed consent of the patient prior to surgical procedures is obligatory. A good and informative communication improves patients' understanding and confidence, thus may strengthen the patient-doctor relationship. The aim of our study was to investigate the usefulness of additional stereoscopic visualization of patient-specific imaging during informed consent conversation., Methods: Patients scheduled for a brain tumor surgery were screened for this study prospectively. The primary exclusion criteria were cognitive or visual impairments. The participants were randomized into two groups. The first group underwent a conventional surgical informed consent performed by a neurosurgeon including a demonstration of the individual MRI on a 2D computer screen. The second group received an additional stereoscopic visualization of the same imaging to explain the pathology more in-depth. The patients were then asked to fill in a questionnaire after each part. This questionnaire was designed to assess the potential information gained from the patients with details on the anatomical location of the tumor as well as the surgical procedure and possible complications. Patients' subjective impression about the informed consent was assessed using a 5-point Likert scale., Results: A total of 27 patients were included in this study. After additional stereoscopic visualization, no significant increase in patient understanding was found for either objective criteria or subjective assessment. Participants' anxiety was not increased by stereoscopic visualization. Overall, patients perceived stereoscopic imaging as helpful from a subjective perspective. Confidence in the department was high in both groups., Conclusion: Stereoscopic visualization of MRI images within informed consent conversation did not improve the objective understanding of the patients in our series. Although no objective anatomical knowledge gain was noted in this series, patients felt that the addition of stereoscopic visualization improved their overall understanding. It therefore potentially increases patient confidence in treatment decisions., (© 2023. The Author(s).)

Background: The medical technical innovations over the last decade have made operations in the highly sensitive regions of the brain much safer., Objective: Presentation of how far computer assistance and robotics have become incorporated into clinical neurosurgery., Material and Method: Evaluation of the scientific literature and analysis of the certification status of the corresponding medical devices., Results: The rapid development of computer technology and the switch to digital imaging has led to the widespread introduction of neurosurgical planning software and intraoperative neuronavigation. In the field of robotics, the penetration into clinical neurosurgery is currently still largely limited to the automatic setting of trajectories., Conclusion: The digitalization of imaging has fundamentally transformed neurosurgery. In the field of cranial neurosurgery, computer-assisted procedures can now be distinguished from noncomputer-assisted procedures only in a handful of cases. In the coming years important innovations for the clinical implementation can be expected in the field of robotics., (© 2023. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Background: Two statistical models have been established to evaluate characteristics associated with postoperative motor outcome in patients with glioma associated to the motor cortex (M1) or the corticospinal tract (CST). One model is based on a clinicoradiological prognostic sum score (PrS) while the other one relies on navigated transcranial magnetic stimulation (nTMS) and diffusion-tensor-imaging (DTI) tractography. The objective was to compare the models regarding their prognostic value for postoperative motor outcome and extent of resection (EOR) with the aim of developing a combined, improved model., Methods: We retrospectively analyzed a consecutive prospective cohort of patients who underwent resection for motor associated glioma between 2008 and 2020, and received a preoperative nTMS motor mapping with nTMS-based diffusion tensor imaging tractography. The primary outcomes were the EOR and the motor outcome (on the day of discharge and 3 months postoperatively according to the British Medical Research Council (BMRC) grading). For the nTMS model, the infiltration of M1, tumor-tract distance (TTD), resting motor threshold (RMT) and fractional anisotropy (FA) were assesed. For the PrS score (ranging from 1 to 8, lower scores indicating a higher risk), we assessed tumor margins, volume, presence of cysts, contrast agent enhancement, MRI index (grading white matter infiltration), preoperative seizures or sensorimotor deficits., Results: Two hundred and three patients with a median age of 50 years (range: 20-81 years) were analyzed of whom 145 patients (71.4%) received a GTR. The rate of transient new motor deficits was 24.1% and of permanent new motor deficits 18.8%. The nTMS model demonstrated a good discrimination ability for the short-term motor outcome at day 7 of discharge (AUC = 0.79, 95 %CI: 0.72-0.86) and the long-term motor outcome after 3 months (AUC = 0.79, 95 %CI: 0.71-0.87). The PrS score was not capable to predict the postoperative motor outcome in this cohort but was moderately associated with the EOR (AUC = 0.64; CI 0.55-0.72). An improved, combined model was calculated to predict the EOR more accurately (AUC = 0.74, 95 %CI: 0.65-0.83)., Conclusion: The nTMS model was superior to the clinicoradiological PrS model for potentially predicting the motor outcome. A combined, improved model was calculated to estimate the EOR. Thus, patient counseling and surgical planning in patients with motor-associated tumors should be performed using functional nTMS data combined with tractography., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Three-dimensional exoscopes have been designed to overcome certain insufficiencies of operative microscopes. We aimed to explore the clinical use in various spinal surgeries. We performed surgery on patients with different spine entities in a neurosurgical department according to the current standard operating procedures over a 4-week period of time. The microsurgical part has been performed with Aesculap AEOS 3D microscope. Three neurosurgeons with different degree of surgical expertise completed a questionnaire with 43 items based on intraoperative handling and feasibility after the procedures. We collected and analyzed data from seventeen patients (35% male/65% female) with a median age of 70 years [CI 47-86] and median BMI of 25.8 kg/m 2 [range 21-33]. We included a variety of spinal pathologies (10 degenerative, 4 tumor and 3 infectious cases) with different level of complexity. Regarding setup conflicts we observed issues with adjustment of the monitor position or while using additional equipment (e.g. fluoroscopy in fusion surgery) (p = 0.007/p = 0.001). However image resolution and sharpness as well as 3D-depth perception were completely satisfactory for all surgeons in all procedures. The utilization of the exoscopic arm was easy for 76.5% of the surgeons, and all of them declared a significant improvement of the surgical corridor. The 3D-exoscope implementation appears to achieve very satisfactory results in spinal procedures especially with minimally invasive approaches., (© 2022. The Author(s).)

Introduction: This study explores the feasibility of implementing a tractography-based navigated transcranial magnetic stimulation (nTMS) language mapping protocol targeting cortical terminations of the arcuate fasciculus (AF). We compared the results and distribution of errors from the new protocol to an established perisylvian nTMS protocol that stimulated without any specific targeting over the entire perisylvian cortex., Methods: Sixty right-handed patients with language-eloquent brain tumors were examined in this study with one half of the cohort receiving the tractographybased protocol and the other half receiving the perisylvian protocol. Probabilistic tractography using MRtrix3 was performed for patients in the tractography-based group to identify the AF's cortical endpoints. nTMS mappings were performed and resulting language errors were classified into five psycholinguistic groups., Results: Tractography and nTMS were successfully performed in all patients. The tractogram-based group showed a significantly higher median overall ER than the perisylvian group (3.8% vs. 2.9% p <.05). The median ER without hesitation errors in the tractogram-based group was also significantly higher than the perisylvian group (2.0% vs. 1.4%, p <.05). The ERs by error type showed no significant differences between protocols except in the no response ER, with a higher median ER in the tractogram-based group (0.4% vs. 0%, p <.05). Analysis of ERs based on the Corina cortical parcellation system showed especially high nTMS ERs over the posterior middle temporal gyrus (pMTG) in the perisylvian protocol and high ERs over the middle and ventral postcentral gyrus (vPoG), the opercular inferior frontal gyrus (opIFG) and the ventral precentral gyrus (vPrG) in the tractography-based protocol., Discussion: By considering the white matter anatomy and performing nTMS on the cortical endpoints of the AF, the efficacy of nTMS in disrupting patients' object naming abilities was increased. The newly introduced method showed proof of concept and resulted in AF-specific ERs and noninvasive cortical language maps, which could be applied to additional fiber bundles related to the language network in future nTMS studies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Reisch, Böttcher, Tuncer, Schneider, Vajkoczy, Picht and Fekonja.)

Objective: Surgical resection of gliomas involving the supplementary motor area (SMA) frequently results in SMA syndrome, a symptom complex characterized by transient akinesia and mutism. Because the factors influencing patient functional outcomes after surgery remain elusive, the authors investigated network-based predictors in a multicentric cohort of glioma patients., Methods: The participants were 50 patients treated for glioma located in the SMA at one of the three centers participating in the study. Postoperative functional outcomes (motor deficits, mutism) and duration of symptoms were assessed during hospitalization. Long-term outcome was assessed 3 months after surgery. MRI-based lesion-symptom mapping was performed to estimate the severity of gray matter damage and white matter disconnection., Results: The median duration of acute symptoms was 3 days (range 1-42 days). Long-term deficits involving fine motor movements and speech were found at follow-up in 27 patients (54%). Disconnection of the central callosal fibers was associated with prolonged acute symptoms (p < 0.05). Postoperative mutism was significantly related to disconnection severity of the left frontopontine tract, frontal aslant tract, cingulum, and corticostriatal tract (p < 0.05). Disconnection of midposterior callosal fibers and lesion loads within the left medial Brodmann area 4 were associated with long-term motor deficits (p < 0.05)., Conclusions: This study provides evidence for the pathophysiology and predictive factors of postoperative SMA syndrome by demonstrating the relation of the disconnection of callosal fibers with prolonged symptom duration (central segment) and long-term motor deficits (midposterior segment). These data may be useful for presurgical risk assessment and adequate consultation for patients prior to undergoing resection of glioma located within the SMA region.

Objective: Training of residents is an essential but time-consuming and costly task in the surgical disciplines. During the coronavirus disease 2019 pandemic, surgical education became even more challenging because of the reduced caseload due to the increased shift to corona care. In this context, augmented 360° 3D virtual reality (VR) videos of surgical procedures enable effective off-site training through virtual participation in the surgery. The goal of this study was to establish and evaluate 360° 3D VR operative videos for neurosurgical training., Methods: Using a 360° camera, the authors recorded three standard neurosurgical procedures: a lumbar discectomy, brain metastasis resection, and clipping of an aneurysm. Combined with the stereoscopic view of the surgical microscope, 7- to 10-minute 360° 3D VR videos augmented with annotations, overlays, and commentary were created. These videos were then presented to the neurosurgical residents at the authors' institution using a head-mounted display. Before viewing the videos, the residents were asked to fill out a questionnaire indicating their VR experience and self-assessment of surgical skills regarding the specific procedure. After watching the videos, the residents completed another questionnaire to evaluate their quality and usefulness. The parameters were scaled with a 5-point Likert scale., Results: Twenty-two residents participated in this study. The mean years of experience of the participants in neurosurgery was 3.2 years, ranging from the 1st through the 7th year of training. Most participants (86.4%) had no or less than 15 minutes of VR experience. The overall quality of the videos was rated good to very good. Immersion, the feeling of being in the operating room, was high, and almost all participants (91%) stated that 360° VR videos provide a useful addition to the neurosurgical training. VR sickness was negligible in the cohort., Conclusions: In this study, the authors demonstrated the feasibility and high acceptance of augmented 360° 3D VR videos in neurosurgical training. Augmentation of 360° videos with complementary and interactive content has the potential to effectively support trainees in acquiring conceptual knowledge. Further studies are necessary to investigate the effectiveness of their use in improving surgical skills.

Along tract statistics enables white matter characterization using various diffusion MRI metrics. These diffusion models reveal detailed insights into white matter microstructural changes with development, pathology and function. Here, we aim at assessing the clinical utility of diffusion MRI metrics along the corticospinal tract, investigating whether motor glioma patients can be classified with respect to their motor status. We retrospectively included 116 brain tumour patients suffering from either left or right supratentorial, unilateral World Health Organization Grades II, III and IV gliomas with a mean age of 53.51 ± 16.32 years. Around 37% of patients presented with preoperative motor function deficits according to the Medical Research Council scale. At group level comparison, the highest non-overlapping diffusion MRI differences were detected in the superior portion of the tracts' profiles. Fractional anisotropy and fibre density decrease, apparent diffusion coefficient axial diffusivity and radial diffusivity increase. To predict motor deficits, we developed a method based on a support vector machine using histogram-based features of diffusion MRI tract profiles (e.g. mean, standard deviation, kurtosis and skewness), following a recursive feature elimination method. Our model achieved high performance (74% sensitivity, 75% specificity, 74% overall accuracy and 77% area under the curve). We found that apparent diffusion coefficient, fractional anisotropy and radial diffusivity contributed more than other features to the model. Incorporating the patient demographics and clinical features such as age, tumour World Health Organization grade, tumour location, gender and resting motor threshold did not affect the model's performance, revealing that these features were not as effective as microstructural measures. These results shed light on the potential patterns of tumour-related microstructural white matter changes in the prediction of functional deficits., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Guarantors of Brain.)

Object: Recent studies demonstrated that gross total resection of brain metastases cannot always be achieved. Subtotal resection (STR) can result in an early recurrence and might affect patient survival. We initiated a prospective observational study to establish a MRI-based risk assessment for incomplete resection of brain metastases., Methods: All patients in whom ≥1 brain metastasis was resected were prospectively included in this study (DRKS ID: DRKS00021224; Nov 2020 - Nov 2021). An interdisciplinary board of neurosurgeons and neuroradiologists evaluated the pre- and postoperative MRI (≤48h after surgery) for residual tumor. Extensive neuroradiological analyses were performed to identify risk factors for an unintended STR which were integrated into a regression tree analysis to determine the patients' individual risk for a STR., Results: We included 150 patients (74 female; mean age: 61 years), in whom 165 brain metastases were resected. A STR was detected in 32 cases (19.4%) (median residual tumor volume: 1.36ml, median EOR rel : 93.6%), of which 6 (3.6%) were intended STR (median residual tumor volume: 3.27ml, median EOR rel : 67.3%) - mainly due to motor-eloquent location - and 26 (15.8%) were unintended STR (uSTR) (median residual tumor volume: 0.64ml, median EOR rel : 94.7%). The following risk factors for an uSTR could be identified: subcortical metastasis ≥5mm distant from cortex, diffuse contrast agent enhancement, proximity to the ventricles, contact to falx/tentorium and non-transcortical approaches. Regression tree analysis revealed that the individual risk for an uSTR was mainly associated to the distance from the cortex (distance ≥5mm vs. <5mm: OR 8.0; 95%CI: 2.7 - 24.4) and the contrast agent patterns (diffuse vs. non-diffuse in those with distance ≥5mm: OR: 4.2; 95%CI: 1.3 - 13.7). The preoperative tumor volume was not substantially associated with the extent of resection., Conclusions: Subcortical metastases ≥5mm distant from cortex with diffuse contrast agent enhancement showed the highest incidence of uSTR. The proposed MRI-based assessment allows estimation of the individual risk for uSTR and can help indicating intraoperative imaging., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Rosenstock, Pöser, Wasilewski, Bauknecht, Grittner, Picht, Misch, Onken and Vajkoczy.)

Objective: With a growing appreciation for interindividual anatomical variability and patient-specific brain connectivity, advanced imaging sequences offer the opportunity to directly visualize anatomical targets for deep brain stimulation (DBS). The lack of quantitative evidence demonstrating their clinical utility, however, has hindered their broad implementation in clinical practice., Methods: Using fast gray matter acquisition T1 inversion recovery (FGATIR) sequences, the present study identified a thalamic hypointensity that holds promise as a visual marker in DBS. To validate the clinical utility of the identified hypointensity, we retrospectively analyzed 65 patients (26 female, mean age = 69.1 ± 12.7 years) who underwent DBS in the treatment of essential tremor. We characterized its neuroanatomical substrates and evaluated the hypointensity's ability to predict clinical outcome using stimulation volume modeling and voxelwise mapping. Finally, we determined whether the hypointensity marker could predict symptom improvement on a patient-specific level., Results: Anatomical characterization suggested that the identified hypointensity constituted the terminal part of the dentatorubrothalamic tract. Overlap between DBS stimulation volumes and the hypointensity in standard space significantly correlated with tremor improvement (R 2  = 0.16, p = 0.017) and distance to hotspots previously reported in the literature (R 2  = 0.49, p = 7.9e-4). In contrast, the amount of variance explained by other anatomical atlas structures was reduced. When accounting for interindividual neuroanatomical variability, the predictive power of the hypointensity increased further (R 2  = 0.37, p = 0.002)., Interpretation: Our findings introduce and validate a novel imaging-based marker attainable from FGATIR sequences that has the potential to personalize and inform targeting and programming in DBS for essential tremor. ANN NEUROL 2022;91:613-628., (© 2022 The Authors. Annals of Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

Stereoscopic imaging has increasingly been used in anatomical teaching and neurosurgery. The aim of our study was to analyze the potential utility of stereoscopic imaging as a tool for memorizing neurosurgical patient cases compared to conventional monoscopic visualization. A total of 16 residents and 6 consultants from the Department of Neurosurgery at Charité - Universitätsmedizin Berlin were recruited for the study. They were divided into two equally experienced groups. A comparative analysis of both imaging modalities was conducted in which four different cases were assessed by the participants. Following the image assessment, two questionnaires, one analyzing the subjective judgment using the 5-point Likert Scale and the other assessing the memorization and anatomical accuracy, were completed by all participants. Both groups had the same median year of experience (5) and stereoacuity (≤ 75 s of arc). The analysis of the first questionnaire demonstrated significant subjective superiority of the monoscopic imaging in evaluation of the pathology (median: monoscopic: 4; stereoscopic: 3; p = 0.020) and in handling of the system (median: monoscopic: 5; stereoscopic: 2; p < 0.001). The second questionnaire showed that the anatomical characterization of the pathologies was comparable between both visualization methods. Most participants rated the stereoscopic visualization as worse compared to the monoscopic visualization, probably due to a lack of familiarity with the newer technique. Stereoscopic imaging, however, was not objectively inferior to traditional monoscopic imaging for anatomical comprehension. Further methodological developments and incorporation in routine clinical workflows will most likely enhance the usability and acceptance of stereoscopic visualization., (© 2021. The Author(s).)

Gliomas that infiltrate networks and systems, such as the motor system, often lead to substantial functional impairment in multiple systems. Network-based statistics (NBS) allow to assess local network differences and graph theoretical analyses enable investigation of global and local network properties. Here, we used network measures to characterize glioma-related decreases in structural connectivity by comparing the ipsi- with the contralesional hemispheres of patients and correlated findings with neurological assessment. We found that lesion location resulted in differential impairment of both short and long connectivity patterns. Network analysis showed reduced global and local efficiency in the ipsilesional hemisphere compared to the contralesional hemispheric networks, which reflect the impairment of information transfer across different regions of a network., (© 2022. The Author(s).)

Low-frequency repetitive transcranial magnetic stimulation (rTMS) is capable of inducing changes in the functional organization of underlying brain regions, however, often at the cost of long stimulation protocols over several weeks. As these protocols can be difficult to implement in clinical settings, the aim of the present pilot study was to show the feasibility and safety of an accelerated low-frequency rTMS protocol applying multiple sessions daily. To this purpose, nine healthy subjects received 14 sessions of rTMS (1 Hz, 30 min, 110% RMT) to the hand motor hotspot. Subjects received stimulation for either 14 days once daily [classical rTMS (c-rTMS)], 7 days twice daily (accelerated rTMS; a-rTMS), or sham stimulation for 14 days once daily (s-rTMS). Daily stimulation sessions in the a-rTMS group were delivered with a 90-min break in between. In total, 74% of rTMS sessions in the c-rTMS group, 89% in the a-rTMS group, and 98% in the s-rTMS group were free of any side effects. Brief headaches and fatigue in stimulated muscle groups were the most frequent side effects. All side effects were reported to be at maximum mild and of short duration. Thus, accelerated low-frequency rTMS of the motor cortex seems to be a safe and feasible method, previously shown to induce a functional reorganization of the motor system. By shortening treatment duration in days, this approach can potentially make rTMS protocols more accessible to a wider range of patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Engelhardt, Kimmel, Raffa, Conti and Picht.)

Exoscopic surgery promises alleviation of physical strain, improved intraoperative visualization and facilitation of the clinical workflow. In this prospective observational study, we investigate the clinical usability of a novel 3D4K-exoscope in routine neurosurgical interventions. Questionnaires on the use of the exoscope were carried out. Exemplary cases were additionally video-documented. All participating neurosurgeons (n = 10) received initial device training. Changing to a conventional microscope was possible at all times. A linear mixed model was used to analyse the impact of time on the switchover rate. For further analysis, we dichotomized the surgeons in a frequent (n = 1) and an infrequent (n = 9) user group. A one-sample Wilcoxon signed rank test was used to evaluate, if the number of surgeries differed between the two groups. Thirty-nine operations were included. No intraoperative complications occurred. In 69.2% of the procedures, the surgeon switched to the conventional microscope. While during the first half of the study the conversion rate was 90%, it decreased to 52.6% in the second half (p = 0.003). The number of interventions between the frequent and the infrequent user group differed significantly (p = 0.007). Main reasons for switching to ocular-based surgery were impaired hand-eye coordination and poor depth perception. The exoscope investigated in this study can be easily integrated in established neurosurgical workflows. Surgical ergonomics improved compared to standard microsurgical setups. Excellent image quality and precise control of the camera added to overall user satisfaction. For experienced surgeons, the incentive to switch from ocular-based to exoscopic surgery greatly varies., (© 2021. The Author(s).)