Improving the efficacy and reliability of rTMS language mapping by increasing the stimulation frequency.

Repetitive TMS (rTMS) with a frequency of 5-10 Hz is widely used for language mapping. However, it may be accompanied by discomfort and is limited in the number and reliability of evoked language errors. We, here, systematically tested the influence of different stimulation frequencies (i.e., 10, 30, and 50 Hz) on tolerability, number, reliability, and cortical distribution of language errors aiming at improved language mapping. 15 right-handed, healthy subjects (m = 8, median age: 29 yrs) were investigated in two sessions, separated by 2-5 days. In each session, 10, 30, and 50 Hz rTMS were applied over the left hemisphere in a randomized order during a picture naming task. Overall, 30 Hz rTMS evoked significantly more errors (20 ± 12%) compared to 50 Hz (12 ± 8%; p <.01), whereas error rates were comparable between 30/50 and 10 Hz (18 ± 11%). Across all conditions, a significantly higher error rate was found in Session 1 (19 ± 13%) compared to Session 2 (13 ± 7%, p <.05). The error rate was poorly reliable between sessions for 10 (intraclass correlation coefficient, ICC = .315) and 30 Hz (ICC = .427), whereas 50 Hz showed a moderate reliability (ICC = .597). Spatial reliability of language errors was low to moderate with a tendency toward increased reliability for higher frequencies, for example, within frontal regions. Compared to 10 Hz, both, 30 and 50 Hz were rated as less painful. Taken together, our data favor the use of rTMS-protocols employing higher frequencies for evoking language errors reliably and with reduced discomfort, depending on the region of interest.

Invasive versus non-invasive mapping of the motor cortex.

Precise and comprehensive mapping of somatotopic representations in the motor cortex is clinically essential to achieve maximum resection of brain tumours whilst preserving motor function, especially since the current gold standard, that is, intraoperative direct cortical stimulation (DCS), holds limitations linked to the intraoperative setting such as time constraints or anatomical restrictions. Non-invasive techniques are increasingly relevant with regard to pre-operative risk-assessment. Here, we assessed the congruency of neuronavigated transcranial magnetic stimulation (nTMS) and functional magnetic resonance imaging (fMRI) with DCS. The motor representations of the hand, the foot and the tongue regions of 36 patients with intracranial tumours were mapped pre-operatively using nTMS and fMRI and by intraoperative DCS. Euclidean distances (ED) between hotspots/centres of gravity and (relative) overlaps of the maps were compared. We found significantly smaller EDs (11.4 ± 8.3 vs. 16.8 ± 7.0 mm) and better spatial overlaps (64 ± 38% vs. 37 ± 37%) between DCS and nTMS compared with DCS and fMRI. In contrast to DCS, fMRI and nTMS mappings were feasible for all regions and patients without complications. In summary, nTMS seems to be the more promising non-invasive motor cortex mapping technique to approximate the gold standard DCS results.

Cortical Inhibition of Face and Jaw Muscle Activity and Discomfort Induced by Repetitive and Paired-Pulse TMS During an Overt Object Naming Task.

Modulatory effects of transcranial magnetic stimulation (TMS) strongly depend on the stimulation parameters. Here, we compared the immediate, task-locked inhibitory effects on speech-related muscles and the tolerability of different TMS protocols during a language production task. Repetitive TMS (rTMS) and paired-pulse TMS (PP) were applied in 13 healthy subjects over the primary motor cortex (M1) during a finger-tapping/tongue-twisting tasks. The lowest subject-specific TMS intensity leading to movement disruptions was used for TMS over left-sided speech-related areas during picture naming. Here, time-locked PP and rTMS (10/30/50 Hz; randomized sequence) were applied. Cortical silent periods (cSPs) were analyzed from electromyography obtained from various face muscles. 30 Hz- and 50 Hz-rTMS reliably evoked tongue movement disruption (ICC = 0.65) at lower rTMS intensities compared to 10 Hz-rTMS or PP. CSPs were elicited from the left hemisphere by all TMS protocols, most reliably by PP (p < 0.001). Also, cSPs with longest durations were induced by PP. Exploratory analyses of PP suggest that the trials with strongest motor inhibitory effects (presence of cSP) were associated with more articulatory naming errors, hence hinting at the utility of TMS-elicited, facial cSP for mapping of language production areas. Higher-frequency rTMS and PP evoked stronger inhibitory effects as compared to 10 Hz-rTMS during a language task, thus enabling a probably more efficient and tolerable routine for language mapping. The spatial distribution of cranial muscle cSPs implies that TMS might affect not only M1, but also distant parts of the language network.

Short- and long-term reliability of language fMRI.

When using functional magnetic resonance imaging (fMRI) for mapping important language functions, a high test-retest reliability is mandatory, both in basic scientific research and for clinical applications. We, therefore, systematically tested the short- and long-term reliability of fMRI in a group of healthy subjects using a picture naming task and a sparse-sampling fMRI protocol. We hypothesized that test-retest reliability might be higher for (i) speech-related motor areas than for other language areas and for (ii) the short as compared to the long intersession interval. 16 right-handed subjects (mean age: 29 years) participated in three sessions separated by 2-6 (session 1 and 2, short-term) and 21-34 days (session 1 and 3, long-term). Subjects were asked to perform the same overt picture naming task in each fMRI session (50 black-white images per session). Reliability was tested using the following measures: (i) Euclidean distances (ED) between local activation maxima and Centers of Gravity (CoGs), (ii) overlap volumes and (iii) voxel-wise intraclass correlation coefficients (ICCs). Analyses were performed for three regions of interest which were chosen based on whole-brain group data: primary motor cortex (M1), superior temporal gyrus (STG) and inferior frontal gyrus (IFG). Our results revealed that the activation centers were highly reliable, independent of the time interval, ROI or hemisphere with significantly smaller ED for the local activation maxima (6.45 ± 1.36 mm) as compared to the CoGs (8.03 ± 2.01 mm). In contrast, the extent of activation revealed rather low reliability values with overlaps ranging from 24% (IFG) to 56% (STG). Here, the left hemisphere showed significantly higher overlap volumes than the right hemisphere. Although mean ICCs ranged between poor (ICC<0.5) and moderate (ICC 0.5-0.74) reliability, highly reliable voxels (ICC>0.75) were found for all ROIs. Voxel-wise reliability of the different ROIs was influenced by the intersession interval. Taken together, we could show that, despite of considerable ROI-dependent variations of the extent of activation over time, highly reliable centers of activation can be identified using an overt picture naming paradigm.

Structural connectome-based predictive modeling of cognitive deficits in treated glioma patients.

Background: In glioma patients, tumor growth and subsequent treatments are associated with various types of brain lesions. We hypothesized that cognitive functioning in these patients critically depends on the maintained structural connectivity of multiple brain networks. Methods: The study included 121 glioma patients (median age, 52 years; median Eastern Cooperative Oncology Group performance score 1; CNS-WHO Grade 3 or 4) after multimodal therapy. Cognitive performance was assessed by 10 tests in 5 cognitive domains at a median of 14 months after treatment initiation. Hybrid amino acid PET/MRI using the tracer O-(2-[18F]fluoroethyl)-L-tyrosine, a network-based cortical parcellation, and advanced tractography were used to generate whole-brain fiber count-weighted connectivity matrices. The matrices were applied to a cross-validated machine-learning model to identify predictive fiber connections (edges), critical cortical regions (nodes), and the networks underlying cognitive performance. Results: Compared to healthy controls (n = 121), patients' cognitive scores were significantly lower in 9 cognitive tests. The models predicted the scores of 7/10 tests (median correlation coefficient, 0.47; range, 0.39-0.57) from 0.6% to 5.4% of the matrix entries; 84% of the predictive edges were between nodes of different networks. Critically involved cortical regions (≥10 adjacent edges) included predominantly left-sided nodes of the visual, somatomotor, dorsal/ventral attention, and default mode networks. Highly critical nodes (≥15 edges) included the default mode network's left temporal and bilateral posterior cingulate cortex. Conclusions: These results suggest that the cognitive performance of pretreated glioma patients is strongly related to structural connectivity between multiple brain networks and depends on the integrity of known network hubs also involved in other neurological disorders.

Digital participation of brain tumour patients in the assessment and treatment of communication disorders.

Introduction: Communication deficits have a severe impact on our social interactions and health-related quality of life. Subtle communication deficits are frequently overlooked or neglected in brain tumour patients, due to insufficient diagnostics. Digital tools may represent a valuable adjunct to the conventional assessment or therapy setting but might not be readily suitable for every patient. Methods: This article summarises results of three surveys on the readiness for telemedicine among (a) patients diagnosed with high-grade glioma, (b) matched controls, and (c) speech and language therapists. The respective surveys assessed the motivation for participation in telemedical assessments and supposed influencing factors, and the use potential of digital assessment and therapy technologies in daily routine, with a spotlight on brain tumour patients and the future prospects of respective telemedical interventions. Respondents included 56 high-grade glioma patients (age median: 59 years; 48% males), 73 propensity-score matched neurologically healthy controls who were instructed to imagine themselves with a severe disease, and 23 speech and language therapists (61% <35 years; all females). Results and discussion: The vast majority of the interviewed high-grade glioma (HGG) patients was open to digitisation, felt well-equipped and sufficiently skilled. The factorial analysis showed that digital offers would be of particular interest for patients in reduced general health condition (p = 0.03) and those who live far from specialised treatment services (p = 0.03). The particular motivation of these subgroups seemed to outweigh the effects of age, equipment and internet skills, which were only significant in the control cohort. The therapists' survey demonstrated a broad consensus on the need for improving the therapy access of brain tumour patients (64%) and strengthening their respective digital participation (78%), although digitisation seems to have yet hardly entered the therapists' daily practise. In summary, the combined results of the surveys call for a joint effort to enhance the prerequisites for digital participation of patients with neurogenic communication disorders, particularly in the context of heavily burdened HGG patients with limited mobility.

Alterations in white matter fiber density associated with structural MRI and metabolic PET lesions following multimodal therapy in glioma patients.

Background: In glioma patients, multimodality therapy and recurrent tumor can lead to structural brain tissue damage characterized by pathologic findings in MR and PET imaging. However, little is known about the impact of different types of damage on the fiber architecture of the affected white matter. Patients and methods: This study included 121 pretreated patients (median age, 52 years; ECOG performance score, 0 in 48%, 1-2 in 51%) with histomolecularly characterized glioma (WHO grade IV glioblastoma, n=81; WHO grade III anaplastic astrocytoma, n=28; WHO grade III anaplastic oligodendroglioma, n=12), who had a resection, radiotherapy, alkylating chemotherapy, or combinations thereof. After a median follow-up time of 14 months (range, 1-214 months), anatomic MR and O-(2-[18F]fluoroethyl)-L-tyrosine (FET) PET images were acquired on a 3T hybrid PET/MR scanner. Post-therapeutic findings comprised resection cavities, regions with contrast enhancement or increased FET uptake and T2/FLAIR hyperintensities. Local fiber density was determined from high angular-resolution diffusion-weighted imaging and advanced tractography methods. A cohort of 121 healthy subjects selected from the 1000BRAINS study matched for age, gender and education served as a control group. Results: Lesion types differed in both affected tissue volumes and relative fiber densities compared to control values (resection cavities: median volume 20.9 mL, fiber density 16% of controls; contrast-enhanced lesions: 7.9 mL, 43%; FET uptake areas: 30.3 mL, 49%; T2/FLAIR hyperintensities: 53.4 mL, 57%, p<0.001). In T2/FLAIR-hyperintense lesions caused by peritumoral edema due to recurrent glioma (n=27), relative fiber density was as low as in lesions associated with radiation-induced gliosis (n=13, 48% vs. 53%, p=0.17). In regions with pathologically increased FET uptake, local fiber density was inversely related (p=0.005) to the extent of uptake. Total fiber loss associated with contrast-enhanced lesions (p=0.006) and T2/FLAIR hyperintense lesions (p=0.013) had a significant impact on overall ECOG score. Conclusions: These results suggest that apart from resection cavities, reduction in local fiber density is greatest in contrast-enhancing recurrent tumors, but total fiber loss induced by edema or gliosis has an equal detrimental effect on the patients' performance status due to the larger volume affected.

Surgery of Motor Eloquent Glioblastoma Guided by TMS-Informed Tractography: Driving Resection Completeness Towards Prolonged Survival.

Background: Surgical treatment of patients with glioblastoma affecting motor eloquent brain regions remains critically discussed given the risk-benefit dilemma of prolonging survival at the cost of motor-functional damage. Tractography informed by navigated transcranial magnetic stimulation (nTMS-informed tractography, TIT) provides a rather robust estimate of the individual location of the corticospinal tract (CST), a highly vulnerable structure with poor functional reorganisation potential. We hypothesised that by a more comprehensive, individualised surgical decision-making using TIT, tumours in close relationship to the CST can be resected with at least equal probability of gross total resection (GTR) than less eloquently located tumours without causing significantly more gross motor function harm. Moreover, we explored whether the completeness of TIT-aided resection translates to longer survival. Methods: A total of 61 patients (median age 63 years, m = 34) with primary glioblastoma neighbouring or involving the CST were operated on between 2010 and 2015. TIT was performed to inform surgical planning in 35 of the patients (group T; vs. 26 control patients). To achieve largely unconfounded group comparisons for each co-primary outcome (i.e., gross-motor functional worsening, GTR, survival), (i) uni- and multivariate regression analyses were performed to identify features of optimal outcome prediction; (ii), optimal propensity score matching (PSM) was applied to balance those features pairwise across groups, followed by (iii) pairwise group comparison. Results: Patients in group T featured a significantly higher lesion-CST overlap compared to controls (8.7 ± 10.7% vs. 3.8 ± 5.7%; p = 0.022). The frequency of gross motor worsening was higher in group T, albeit non-significant (n = 5/35 vs. n = 0/26; p = 0.108). PSM-based paired-sample comparison, controlling for the confounders of preoperative tumour volume and vicinity to the delicate vasculature of the insula, showed higher GTR rates in group T (77% vs. 69%; p = 0.025), particularly in patients with a priori intended GTR (87% vs. 78%; p = 0.003). This translates into a prolonged PFS in the same PSM subgroup (8.9 vs. 5.8 months; p = 0.03), with GTR representing the strongest predictor of PFS (p = 0.001) and OS (p = 0.0003) overall. Conclusion: The benefit of TIT-aided GTR appears to overcome the drawbacks of potentially elevated motor functional risk in motor eloquent tumour localisation, leading to prolonged survival of patients with primary glioblastoma close to the CST.

Two Decades of Brain Tumour Imaging with O-(2-[18F]fluoroethyl)-L-tyrosine PET: The Forschungszentrum Jülich Experience.

O-(2-[18F]fluoroethyl)-L-tyrosine (FET) is a widely used amino acid tracer for positron emission tomography (PET) imaging of brain tumours. This retrospective study and survey aimed to analyse our extensive database regarding the development of FET PET investigations, indications, and the referring physicians' rating concerning the role of FET PET in the clinical decision-making process. Between 2006 and 2019, we performed 6534 FET PET scans on 3928 different patients against a backdrop of growing demand for FET PET. In 2019, indications for the use of FET PET were as follows: suspected recurrent glioma (46%), unclear brain lesions (20%), treatment monitoring (19%), and suspected recurrent brain metastasis (13%). The referring physicians were neurosurgeons (60%), neurologists (19%), radiation oncologists (11%), general oncologists (3%), and other physicians (7%). Most patients travelled 50 to 75 km, but 9% travelled more than 200 km. The role of FET PET in decision-making in clinical practice was evaluated by a questionnaire consisting of 30 questions, which was filled out by 23 referring physicians with long experience in FET PET. Fifty to seventy per cent rated FET PET as being important for different aspects of the assessment of newly diagnosed gliomas, including differential diagnosis, delineation of tumour extent for biopsy guidance, and treatment planning such as surgery or radiotherapy, 95% for the diagnosis of recurrent glioma, and 68% for the diagnosis of recurrent brain metastases. Approximately 50% of the referring physicians rated FET PET as necessary for treatment monitoring in patients with glioma or brain metastases. All referring physicians stated that the availability of FET PET is essential and that it should be approved for routine use. Although the present analysis is limited by the fact that only physicians who frequently referred patients for FET PET participated in the survey, the results confirm the high relevance of FET PET in the clinical diagnosis of brain tumours and support the need for its approval for routine use.

Assessment Practice of Patient-Centered Outcomes in Surgical Neuro-Oncology: Survey-Based Recommendations for Clinical Routine.

The psycho-oncological burden related to the diagnosis of an intracranial tumor is often accompanied by neurocognitive deficits and changes in character, overall affecting health-related quality of life (HRQoL) and activities of daily living. Regular administration of adequate screening tools is crucial to ensure a timely detection of needs for support and/or specific interventions. Although efforts have been made to assure the quality of neuro-oncological care, clinical assessment practice of patient-reported outcomes (PROs) remains overall heterogeneous, calling for a concise recommendation tailored to neuro-oncological patients. Therefore, this survey, promoted by the German Society of Neurosurgery, was conducted to evaluate the status quo of health care resources and PRO/neurocognition assessment practices throughout departments of surgical neuro-oncology in Germany. 72/127 (57%) of registered departments participated in the study, including 83% of all university hospital units. A second aim was to shed light on the impact of quality assurance strategies (i.e., department certification as part of an integrative neuro-oncology cancer center; CNOC) on the assessment practice, controlled for interacting structural factors, i.e., university hospital status (UH) and caseload. Despite an overall good to excellent availability of relevant health care structures (psycho-oncologist: 90%, palliative care unit: 97%, neuropsychology: 75%), a small majority of departments practice patient-centered screenings (psycho-oncological burden: 64%, HRQoL: 76%, neurocognition: 58%), however, much less frequently outside the framework of clinical trials. In this context, CNOC affiliation, representing a specific health care quality assurance process, was associated with significantly stronger PRO assessment practices regarding psycho-oncological burden, independent of UH status (common odds ratio=5.0, p=0.03). Nevertheless, PRO/neurocognitive assessment practice was not consistent even across CNOC. The overall most commonly used PRO/neurocognitive assessment tools were the Distress Thermometer (for psycho-oncological burden; 64%), the EORTC QLQ-C30 combined with the EORTC QLQ-BN20 (for HRQoL; 52%) and the Mini-Mental Status Test (for neurocognition; 67%), followed by the Montreal Cognitive Assessment (MoCA; 33%). Accordingly, for routine clinical screening, the authors recommend the Distress Thermometer and the EORTC QLQ-C30 and QLQ-BN20, complemented by the MoCA as a comparatively sensitive yet basic neurocognitive test. This recommendation is intended to encourage more regular, adequate, and standardized routine assessments in neuro-oncological practice.

The Cologne Picture Naming Test for Language Mapping and Monitoring (CoNaT): An Open Set of 100 Black and White Object Drawings.

Language assessment using a picture naming task crucially relies on the interpretation of the given verbal response by the rater. To avoid misinterpretations, a language-specific and linguistically controlled set of unambiguous, clearly identifiable and common object-word pairs is mandatory. We, here, set out to provide an open-source set of black and white object drawings, particularly suited for language mapping and monitoring, e.g., during awake brain tumour surgery or transcranial magnetic stimulation, in German language. A refined set of 100 black and white drawings was tested in two consecutive runs of randomised picture order and was analysed in respect of correct, prompt, and reliable object recognition and naming in a series of 132 healthy subjects between 18 and 84 years (median 25 years, 64% females) and a clinical pilot cohort of 10 brain tumour patients (median age 47 years, 80% males). The influence of important word- and subject-related factors on task performance and reliability was investigated. Overall, across both healthy subjects and patients, excellent correct object naming rates (97 vs. 96%) as well as high reliability coefficients (Goodman-Kruskal's gamma = 0.95 vs. 0.86) were found. However, the analysis of variance revealed a significant, overall negative effect of low word frequency (p < 0.05) and high age (p < 0.0001) on task performance whereas the effect of a low educational level was only evident for the subgroup of 72 or more years of age (p < 0.05). Moreover, a small learning effect was observed across the two runs of the test (p < 0.001). In summary, this study provides an overall robust and reliable picture naming tool, optimised for the clinical use to map and monitor language functions in patients. However, individual familiarisation before the clinical use remains advisable, especially for subjects that are comparatively prone to spontaneous picture naming errors such as older subjects of low educational level and patients with clinically apparent word finding difficulties.

Introduction to spasticity and related mouse models.

Although spasticity is one of the most common causes of motor disability worldwide, its precise definition and pathophysiology remain elusive, which to date renders its experimental targeting tricky. At least in part, this difficulty is caused by heterogeneous phenotypes of spasticity-causing neurological disorders, all causing spasticity by involving upper motor neurons. The most common clinical symptoms are a series of rapid muscle contractions (clonus), an increased muscle tone (hypertonia), and augmented tendon reflex activity (hyperreflexia). This muscle overactivity is due to disturbed inhibition of spinal reflexes following upper motor neuron dysfunction. Despite a range of physical and pharmacological therapies ameliorating the symptoms, their targeted application remains difficult. Therefore, to date, spasticity impacts rehabilitative therapy, and no therapy exists that reverses the pathology completely. In contrast to the incidence and importance of spasticity, only very little pre-clinical work in animal models exists, and this research is focused on the cat or the rat spastic tail model to decipher altered reflexes and excitability of the motor neurons in the spinal cord. Meanwhile, the characterization of spasticity in clinically more relevant mouse models of neurological disorders, such as stroke, remains understudied. Here, we provide a brief introduction into the clinical knowledge and therapy of spasticity and an in-depth review of pre-clinical studies of spasticity in mice including the current experimental challenges for clinical translation.

Lesion-Function Analysis from Multimodal Imaging and Normative Brain Atlases for Prediction of Cognitive Deficits in Glioma Patients.

Cognitive deficits are common in glioma patients following multimodality therapy, but the relative impact of different types and locations of treatment-related brain damage and recurrent tumors on cognition is not well understood. In 121 WHO Grade III/IV glioma patients, structural MRI, O-(2-[18F]fluoroethyl)-L-tyrosine FET-PET, and neuropsychological testing were performed at a median interval of 14 months (range, 1-214 months) after therapy initiation. Resection cavities, T1-enhancing lesions, T2/FLAIR hyperintensities, and FET-PET positive tumor sites were semi-automatically segmented and elastically registered to a normative, resting state (RS) fMRI-based functional cortical network atlas and to the JHU atlas of white matter (WM) tracts, and their influence on cognitive test scores relative to a cohort of matched healthy subjects was assessed. T2/FLAIR hyperintensities presumably caused by radiation therapy covered more extensive brain areas than the other lesion types and significantly impaired cognitive performance in many domains when affecting left-hemispheric RS-nodes and WM-tracts as opposed to brain tissue damage caused by resection or recurrent tumors. Verbal episodic memory proved to be especially vulnerable to T2/FLAIR abnormalities affecting the nodes and tracts of the left temporal lobe. In order to improve radiotherapy planning, publicly available brain atlases, in conjunction with elastic registration techniques, should be used, similar to neuronavigation in neurosurgery.

Accelerated Clustered Sparse Acquisition to Improve Functional MRI for Mapping Language Functions.

BACKGROUND: Functional magnetic resonance imaging (fMRI) is a useful method for noninvasive presurgical functional mapping. However, the scanner environment is inherently unsuitable for the examination of auditory and language functions, due to the loud acoustic noise produced by the scanner. Interleaved acquisition methods alleviate this problem by providing a silent period for stimulus presentation and/or response control (sparse sampling) but at the expense of a diminished amount of data collected. There are possible improvements to these sparse acquisition methods that increase the amount of data by acquiring several images per event (clustered sampling). We tested accelerated clustered fMRI acquisition in comparison with conventional sparse sampling in a pilot study. METHODS: The clustered and sparse acquisition techniques (7.4 minutes scanning time per protocol) were directly compared in 15 healthy subjects (8 men; mean age: 24 ± 3 years) using both a motor (tongue movement) and a language (overt picture-naming) task. Functional imaging data were analyzed using Statistical Parametric Mapping software (SPM12 Wellcome Department of Imaging Neuroscience, London, UK). For both tasks, activation levels were compared and Euclidean distances (EDs) between cluster centers (i.e., local activation maxima and centers of gravity) were calculated. Overlaps and laterality indices were computed for the picture-naming task. In addition, the feasibility of the clustered acquisition protocol in a clinical setting was assessed in one pilot patient. RESULTS: For both tasks, activation levels were higher using the clustered acquisition protocol, reflected by bigger cluster sizes (p < 0.05). Mean ED between cluster centers ranged between 9.9 ± 5.4 mm (left superior temporal gyrus; centers of gravity) and 16.6 ± 13.2 mm (left inferior frontal gyrus; local activation maxima) for the picture-naming task. Overlaps between sparse and clustered acquisition reached 88% (Simpson overlap coefficient). A similar activation pattern for both acquisition methods was also confirmed in the clinical case. CONCLUSION: Despite some drawbacks inherent to the acquisition technique, the clustered sparse sampling protocol showed increased sensitivity for activation in language-related cortical regions with short scanning times. Such scanning techniques may be particularly advantageous for investigating patients with contraindications for long scans (e.g., reduced attention span).

Glioma patients in outpatient care-optimization of psychosocial care in neuro-oncological patients (GLIOPT): Protocol for a cluster randomized controlled trial.

BACKGROUND: Patients with high-grade gliomas (HGG) often suffer from high distress and require psychosocial support. However, due to neurological and neurocognitive deficits, adequate assessment of distress and support needs remains challenging in clinical practice. The objective of the present study is to investigate whether a systematic implementation of signaling questions into the routine outpatient consultation will be helpful to bridge this gap. METHODS/DESIGN: This is a multicenter cluster randomized study with two arms. Randomization is done on a cluster level with 13 hospitals providing regular neuro-oncological outpatient services conducted by neurologists and/or neurosurgeons. The intervention will include an assessment of psychosocial distress of patients in doctor-patient conversation compared to assessment of psychosocial distress via questionnaire (control, standard of care). In total, 616 HGG patients will be enrolled. The outcome will be the number of HGG patients with increased psychosocial distress who receive professional support from psychosocial services. Secondary endpoints are inter alia number of patients reporting psychosocial distress and unmet needs detected correctly by the respective method; quality of life; psychological well-being and burden of the patients before and after doctor-patient consultation; as well as the length of the doctor-patient consultation. DISCUSSION: Patients with HGG are confronted with an oncological diagnosis and at the same time with high symptom burden. This often leads to distress, which is not always adequately recognized and treated. So far, only a limited number of adequate instruments are available to assess HGG patient's distress. Yet, an adequate care and support network might facilitate the course of the disease and tumor therapies for patients. Our hypothesis is that an assessment conducted directly by attending doctors and in which the doctors talk to patients with HGG will be more effective than an assessment via a questionnaire, leading to better identifying patients in need of support. This may lead to an improvement of health care in these patients. Further, this method might be implemented also in other brain tumor patients (e.g., patients with brain metastases). TRIAL REGISTRATION: German Clinical Trials Register, DRKS00018079. Registered on 3rd September 2019.

Functional MRI vs. navigated TMS to optimize M1 seed volume delineation for DTI tractography. A prospective study in patients with brain tumours adjacent to the corticospinal tract.

BACKGROUND: DTI-based tractography is an increasingly important tool for planning brain surgery in patients suffering from brain tumours. However, there is an ongoing debate which tracking approaches yield the most valid results. Especially the use of functional localizer data such as navigated transcranial magnetic stimulation (nTMS) or functional magnetic resonance imaging (fMRI) seem to improve fibre tracking data in conditions where anatomical landmarks are less informative due to tumour-induced distortions of the gyral anatomy. We here compared which of the two localizer techniques yields more plausible results with respect to mapping different functional portions of the corticospinal tract (CST) in brain tumour patients. METHODS: The CSTs of 18 patients with intracranial tumours in the vicinity of the primary motor area (M1) were investigated by means of deterministic DTI. The core zone of the tumour-adjacent hand, foot and/or tongue M1 representation served as cortical regions of interest (ROIs). M1 core zones were defined by both the nTMS hot-spots and the fMRI local activation maxima. In addition, for all patients, a subcortical ROI at the level of the inferior anterior pons was implemented into the tracking algorithm in order to improve the anatomical specificity of CST reconstructions. As intra-individual control, we additionally tracked the CST of the hand motor region of the unaffected, i.e., non-lesional hemisphere, again comparing fMRI and nTMS M1 seeds. The plausibility of the fMRI-ROI- vs. nTMS-ROI-based fibre trajectories was assessed by a-priori defined anatomical criteria. Moreover, the anatomical relationship of different fibre courses was compared regarding their distribution in the anterior-posterior direction as well as their location within the posterior limb of the internal capsule (PLIC). RESULTS: Overall, higher plausibility rates were observed for the use of nTMS- as compared to fMRI-defined cortical ROIs (p < 0.05) in tumour vicinity. On the non-lesional hemisphere, however, equally good plausibility rates (100%) were observed for both localizer techniques. fMRI-originated fibres generally followed a more posterior course relative to the nTMS-based tracts (p < 0.01) in both the lesional and non-lesional hemisphere. CONCLUSION: NTMS achieved better tracking results than fMRI in conditions when the cortical tract origin (M1) was located in close vicinity to a brain tumour, probably influencing neurovascular coupling. Hence, especially in situations with altered BOLD signal physiology, nTMS seems to be the method of choice in order to identify seed regions for CST mapping in patients.