Targeting MYC effector functions in pancreatic cancer by inhibiting the ATPase RUVBL1/2.

OBJECTIVE: The hallmark oncogene MYC drives the progression of most tumours, but direct inhibition of MYC by a small-molecule drug has not reached clinical testing. MYC is a transcription factor that depends on several binding partners to function. We therefore explored the possibility of targeting MYC via its interactome in pancreatic ductal adenocarcinoma (PDAC). DESIGN: To identify the most suitable targets among all MYC binding partners, we constructed a targeted shRNA library and performed screens in cultured PDAC cells and tumours in mice. RESULTS: Unexpectedly, many MYC binding partners were found to be important for cultured PDAC cells but dispensable in vivo. However, some were also essential for tumours in their natural environment and, among these, the ATPases RUVBL1 and RUVBL2 ranked first. Degradation of RUVBL1 by the auxin-degron system led to the arrest of cultured PDAC cells but not untransformed cells and to complete tumour regression in mice, which was preceded by immune cell infiltration. Mechanistically, RUVBL1 was required for MYC to establish oncogenic and immunoevasive gene expression identifying the RUVBL1/2 complex as a druggable vulnerability in MYC-driven cancer. CONCLUSION: One implication of our study is that PDAC cell dependencies are strongly influenced by the environment, so genetic screens should be performed in vitro and in vivo. Moreover, the auxin-degron system can be applied in a PDAC model, allowing target validation in living mice. Finally, by revealing the nuclear functions of the RUVBL1/2 complex, our study presents a pharmaceutical strategy to render pancreatic cancers potentially susceptible to immunotherapy.

Does indocyanine green fluorescence angiography impact the intraoperative choice of procedure in free vascularized medial femoral condyle grafting for scaphoid nonunions?

Background: Free vascularized medial femoral condyle (MFC) bone grafts can lead to increased vascularity of the proximal pole and restore scaphoid architecture in scaphoid nonunions. The intraoperative perfusion assessment of the bone graft is challenging because the conventional clinical examination is difficult. Indocyanine green (ICG) angiography has previously been shown to provide a real-time intraoperative evaluation of soft tissue perfusion in reconstructive surgery. The present study investigated the utility of ICG angiography in patients treated with a free medial femoral condyle graft for scaphoid nonunions. Methods: We performed a retrospective analysis of patients with scaphoid nonunions, in which ICG angiography was used intraoperatively for perfusion assessment. The medical records, radiographs, intraoperative imaging, and operative reports of all patients were reviewed. Intraoperative ICG dye was administered intravenously, and laser angiography was performed to assess bone perfusion. The scaphoid union was examined using postoperative CT scans. Results: Two patients had documented osteonecrosis of the proximal pole at the time of surgery. Four patients received a nonvascularized prior bone graft procedure, and a prior spongiosa graft procedure was performed in one patient. The mean time from injury to the MFC bone graft surgery was 52.7 months, and the mean time from prior failed surgery was 10.4 months. Perfusion of the vascular pedicle of the MFC and the periosteum could be detected in all patients. In two patients, even perfusion of the cancellous bone could be demonstrated by ICG angiography. Following transplantation of the bone graft, patency of the vascular anastomosis and perfusion of the periost were confirmed by ICG angiography in the assessed cases. No additional surgery regarding a salvage procedure for a scaphoid nonunion advanced collapse was necessary for the further course. Conclusion: ICG-angiography has shown to be a promising tool in the treatment of scaphoid nonunion with medial femoral condyle bone grafts. It enables intraoperative decision making by assessment of the microvascular blood supply of the periosteum and the vascular pedicle of the MFC bone graft. Further studies need to evaluate the impact on union rates in a long-term follow-up.

An Innovative Arteriovenous (AV) Loop Breast Cancer Model Tailored for Cancer Research.

Animal models are important tools to investigate the pathogenesis and develop treatment strategies for breast cancer in humans. In this study, we developed a new three-dimensional in vivo arteriovenous loop model of human breast cancer with the aid of biodegradable materials, including fibrin, alginate, and polycaprolactone. We examined the in vivo effects of various matrices on the growth of breast cancer cells by imaging and immunohistochemistry evaluation. Our findings clearly demonstrate that vascularized breast cancer microtissues could be engineered and recapitulate the in vivo situation and tumor-stromal interaction within an isolated environment in an in vivo organism. Alginate-fibrin hybrid matrices were considered as a highly powerful material for breast tumor engineering based on its stability and biocompatibility. We propose that the novel tumor model may not only serve as an invaluable platform for analyzing and understanding the molecular mechanisms and pattern of oncologic diseases, but also be tailored for individual therapy via transplantation of breast cancer patient-derived tumors.

Influence of the autotaxin-lysophosphatidic acid axis on cellular function and cytokine expression in different breast cancer cell lines.

Previous studies provide high evidence that autotaxin (ATX)-lysophosphatidic acid (LPA) signaling through LPA receptors (LPAR) plays an important role in breast cancer initiation, progression, and invasion. However, its specific role in different breast cancer cell lines remains to be fully elucidated to offer improvements in targeted therapies. Within this study, we analyzed in vitro the effect of LPA 18:1 and the LPAR1, LPAR3 (and LPAR2) inhibitor Ki16425 on cellular functions of different human breast cancer cell lines (MDA-MB-231, MDA-MB-468, MCF-7, BT-474, SKBR-3) and the human breast epithelial cell line MCF-10A, as well as Interleukin 8 (IL-8), Interleukin 6 (IL-6) and tumor necrosis factor (TNF)-alpha cytokine secretion after LPA-incubation. ATX-LPA signaling showed a dose-dependent stimulatory effect especially on cellular functions of triple-negative and luminal A breast cancer cell lines. Ki16425 inhibited the LPA-induced stimulation of triple-negative breast cancer and luminal A cell lines in variable intensity depending on the functional assay, indicating the interplay of different LPAR in those assays. IL-8, IL-6 and TNF-alpha secretion was induced by LPA in MDA-MB-468 cells. This study provides further evidence about the role of the ATX-LPA axis in different breast cancer cell lines and might contribute to identify subtypes suitable for a future targeted therapy of the ATX-LPA axis.

The third dimension in perforator mapping-Comparison of Cinematic Rendering and maximum intensity projection in abdominal-based autologous breast reconstruction.

BACKGROUND: Cinematic Rendering (CR) is a recently introduced post-processing three-dimensional (3D) visualization imaging tool. The aim of this study was to assess its clinical value in the preoperative planning of deep inferior epigastric artery perforator (DIEP) or muscle-sparing transverse rectus abdominis myocutaneous (MS-TRAM) flaps, and to compare it with maximum intensity projection (MIP) images. The study presents the first application of CR for perforator mapping prior to autologous breast reconstruction. METHODS: Two senior surgeons independently analyzed CR and MIP images based on computed tomography angiography (CTA) datasets of 20 patients in terms of vascular pedicle characteristics, the possibility to harvest a DIEP or MS-TRAM flap, and the side of the flap harvest. We calculated inter- and intra-observer agreement in order to examine the accordance of both image techniques. RESULTS: We observed a good inter- and intra-observer agreement concerning the type of flap and the side of the flap harvest. However, the agreement on the pedicle characteristics varies depending on the considered variable. Both investigators identified a significantly higher number of perforators with MIP compared with CR (observer 1, p<0.0001 and observer 2, p<0.0385). CONCLUSION: The current study serves as an explorative study, showing first experiences with CR in abdominal-based autologous breast reconstruction. In addition to MIP images, CR might improve the surgeon's understanding of the individual's anatomy. Future studies are required to compare CR with other 3D visualization tools and its possible effects on operative parameters.

Corrigendum: Does indocyanine green fluorescence angiography impact the intraoperative choice of procedure in free vascularized medial femoral condyle grafting for scaphoid non-unions?

[This corrects the article DOI: 10.3389/fsurg.2022.962450.].

Body Contouring Surgery Improves Physical Activity in Patients After Massive Weight Loss-a Retrospective Study.

BACKGROUND: The aim of the study was to compare physical activity (PA) in patients who had undergone massive weight loss (MWL), before and after body contouring procedures. METHODS: All patients undergoing body contouring surgery after MWL between 2007 and 2017 with a minimum follow-up of 6 months after the last procedure were included in this retrospective study. Excluded were those with a body mass index > 35 kg/m2 and those with comorbidities leading to impaired PA. Quality of life (QOL) was assessed using the Moorehead-Ardelt QOL Questionnaire II. Evaluation of PA was obtained with the International Physical Activity Questionnaire (IPAQ) short form and the Freiburg PA Questionnaire. Functional impairment during exercise was analyzed using a self-designed functional impairment score (FIS). RESULTS: In the 45 patients completing the survey (37 female, 8 male), an improvement in QOL (p < 0.001) and PA scored by the IPAQ (p = 0.017) was found. The Freiburg PA Questionnaire showed no difference in PA before and after body contouring surgery (p = 0,274). Furthermore, scores of the FIS indicated a decrease of functional impairment during physical activity after body contouring surgery (p < 0.001). CONCLUSION: Body contouring improves QOL and PA in patients after massive weight loss. The results of our study confirm the important role of plastic surgery in the treatment and maintenance of health of patients with former obesity.

Operating on the Edge? Body Contouring Procedures in Patients with Body Mass Index Greater 35.

BACKGROUND: Body contouring surgery after massive weight loss was shown to ameliorate the patient's quality of life and to enhance physical and psychological well-being. However, numerous patients are still obese when presenting for body contouring surgery, not able to lose additional weight for various reasons. Data regarding general feasibility, outcome, and postoperative complications in obese patients is rare. The aim of this study was to investigate the outcome in body contouring procedures in obese patients. METHODS: A retrospective chart review of 65 cases in 42 patients was performed. Patients with a body mass index (BMI) > 35 kg/m2 at the time of operation were enrolled and all different types of body contouring surgery were included. Complications were classified as major (need for surgical intervention) and minor complications. RESULTS: The median BMI of all patients was 38 kg/m2 (range 35.1-65.1 kg/m2). The majority of performed types of body contouring was abdominal body contouring (panniculectomy n = 27 (42%), abdominoplasty n = 12 (18%)). Complications occurred in 27 cases (41.5%). Twenty-one cases (32.3%) were classified as minor complications, six (9.2%) as major complications. The most common major complications were hematoma and wound dehiscence; the most common minor complication was seroma. CONCLUSION: A reasonable risk for complications is well known in body contouring surgery especially in obese patients. It is imperative to discuss related risks and expected results. Taking several points into account concerning the perioperative management, reduction of major complications is possible even in still obese patients, making body contouring surgery a discussible option.

Language function shows comparable cortical patterns by functional MRI and repetitive nTMS in healthy volunteers.

In preoperative planning, fMRI and repetitive navigated transcranial magnetic stimulation (rTMS) repeatedly revealed differences in the detected language sites, which can be attributed to tumor-induced oxygenation changes impairing the accuracy of fMRI. We therefore compared the accordance of those techniques in healthy subjects using exactly the same tasks in both investigations. 19 healthy right-handed subjects performed object naming, pseudoword reading, verb generation, and action naming during fMRI at 3 T and rTMS. For rTMS language mapping, we stimulated 46 cortical spots over the left hemisphere; each site was stimulated for three times. Language positive points during rTMS for one, two, or three errors out the three stimulations per spot (1/3, 2/3, 3/3) were exported via DICOM, and compared to the positive fMRI clusters. As a result of this comparison, the best correlation was observed between 3/3 errors and fMRI for pseudoword reading and verb generation with t-values of pu < 0.001, uncorrected for multiple comparisons, on average across the whole rTMS-spot map. We found a close spatial agreement between several rTMS-spots (2/3 and 3/3 errors) and fMRI clusters accentuated in the frontal lobe, followed by the parietal lobe and less in the temporal lobe. Compared to the fMRI clusters, there was a higher congruence for 2/3 and 3/3 errors than for 1/3 errors. Overall, results of language mapping in healthy subjects by fMRI and rTMS correspond well yet depending on the used language task.

Non-invasive Mapping of Face Processing by Navigated Transcranial Magnetic Stimulation.

Background: Besides motor and language function, tumor resections within the frontal and parietal lobe have also been reported to cause neuropsychological impairment like prosopagnosia. Objective: Since non-navigated transcranial magnetic stimulation (TMS) has previously been used to map neuropsychological cortical function, this study aims to evaluate the feasibility and spatial discrimination of repetitive navigated TMS (rTMS) mapping for detection of face processing impairment in healthy volunteers. The study was also designed to establish this examination for preoperative mapping in brain tumor patients. Methods: Twenty healthy and purely right-handed volunteers (11 female, 9 male) underwent rTMS mapping for cortical face processing function using 5 Hz/10 pulses. Both hemispheres were investigated randomly with an interval of 2 weeks between mapping sessions. Fifty-two predetermined cortical spots of the whole hemispheres were mapped after baseline measurement. The task consisted of 80 portraits of popular persons, which had to be named while rTMS was applied. Results: In 80% of all subjects rTMS elicited naming errors in the right middle middle frontal gyrus (mMFG). Concerning anomia errors, the highest error rate (35%) was achieved in the bilateral triangular inferior frontal gyrus (trIFG). With regard to similarly or wrongly named persons, we observed 10% error rates mainly in the bilateral frontal lobes. Conclusion: It seems feasible to map the cortical face processing function and to generate face processing impairment via rTMS. The observed localizations are well in accordance with the contemporary literature, and the mapping did not interfere with rTMS-induced language impairment. The clinical usefulness of preoperative mapping has to be evaluated subsequently.

Visualization of subcortical language pathways by diffusion tensor imaging fiber tracking based on rTMS language mapping.

Diffusion tensor imaging fiber tracking (DTI FT) is used to visualize subcortical fiber tracts. Yet, there is no standard at hand to visualize language-involved subcortical fibers reliably. Thus, this study investigates the feasibility of using language-related cortical areas identified via repetitive navigated transcranial magnetic stimulation (rTMS) to seed DTI FT of subcortical language tracts. From 2011 to 2014, 37 patients with left-hemispheric perisylvian lesions were examined. Language-positive rTMS stimulation spots were integrated in the deterministic tractography software (BrainLAB, iPlanNet 3.0) as objects and used as seed regions for DTI FT. Tractography was then performed in each patient with 77 different combinations of fiber lengths (40 - 100 mm) and fractional anisotropy (FA; 0.01 - 0.5). The rTMS-based DTI FT identified all commonly known subcortical language tracts, such as the corticonuclear tract, arcuate fascicle, uncinate fascicle, superior longitudinal fascicle, inferior longitudinal fascicle, arcuate fibers, commissural fibers, corticothalamic fibers, and the fronto-occipital fascicle. In 32 patients (86.5 %), each above-named tract could be visualized, while at least 6 out of these 9 tracts were identified in each patient. A fiber length of 100 mm and an FA of 0.1 or 0.15 provided optimal visualization by revealing 125 and 61 individually tracked fibers per visualized language tract and 90 % and 73 % of all language-related tracts, respectively. This study proves the feasibility of rTMS-based DTI FT for subcortical language tracts, provides suitable settings, and shows its easy and standardizable application for the visualization of every language tract in 86.5 % of patients.

Interhemispheric connectivity revealed by diffusion tensor imaging fiber tracking derived from navigated transcranial magnetic stimulation maps as a sign of language function at risk in patients with brain tumors.

OBJECTIVE Resection of brain tumors in language-eloquent areas entails the risk of postoperative aphasia. It has been demonstrated via navigated transcranial magnetic stimulation (nTMS) that language function can partially shift to the unaffected hemisphere due to tumor-induced plasticity. Therefore, this study was designed to evaluate whether interhemispheric connectivity (IC) detected by nTMS-based diffusion tensor imaging-fiber tracking (DTI-FT) can be used to predict surgery-related aphasia in patients with brain tumors. METHODS Thirty-eight patients with left-sided perisylvian brain lesions underwent cortical language mapping of both hemispheres by nTMS prior to awake surgery. Then, nTMS-based DTI-FT was conducted with a fractional anisotropy (FA) of 0.01 and 0.2 to visualize nTMS-based IC. Receiver operating characteristics were calculated for the prediction of a postoperative (irrespective of the preoperative state) and a new surgery-related aphasia by the presence of detectable IC. RESULTS Language mapping by nTMS was possible in all patients. Seventeen patients (44.7%) suffered from surgery-related worsening of language performance (transient aphasia according to 3-month follow-up in 16 subjects [42.1%]; new permanent aphasia according to 3-month follow-up in 1 patient [2.6%]). Regarding the correlation of aphasia to nTMS-based IC, statistically significant differences were revealed for both evaluated FA values. However, better results were observed for tractography with an FA of 0.2, which led to a specificity of 93% (postoperative aphasia) and 90% (surgery-related aphasia). For postoperative aphasia, the corresponding OR was 0.1282 (95% CI 0.0143-1.1520), and for surgery-related aphasia the OR was 0.1184 (95% CI 0.0208-0.6754). CONCLUSIONS According to these results, IC detected by preoperative nTMS-based DTI-FT might be regarded as a risk factor for surgery-related aphasia, with a specificity of up to 93%. However, because the majority of enrolled patients suffered from transient aphasia postoperatively, it has to be evaluated whether this approach distinctly leads to similar results among patients with permanent language deficits. Despite this restriction, this approach might contribute to individualized patient consultation prior to tumor resection in clinical practice.

Language pathway tracking: comparing nTMS-based DTI fiber tracking with a cubic ROIs-based protocol.

OBJECTIVE Diffusion tensor imaging (DTI) fiber tracking (FT) has been widely used in glioma surgery in recent years. It can provide helpful information about subcortical structures, especially in patients with eloquent space-occupying lesions. This study compared the newly developed navigated transcranial magnetic stimulation (nTMS)-based DTI FT of language pathways with the most reproducible protocol for language pathway tractography, using cubic regions of interest (ROIs) for the arcuate fascicle. METHODS Thirty-seven patients with left-sided perisylvian lesions underwent language mapping by repetitive nTMS. DTI FT was performed using the cubic ROIs-based protocol and the authors' nTMS-based DTI FT approach. The same minimal fiber length and fractional anisotropy were chosen (50 mm and 0.2, respectively). Both protocols were performed with standard clinical tractography software. RESULTS Both methods visualized language-related fiber tracts (i.e., corticonuclear tract, arcuate fascicle, uncinate fascicle, superior longitudinal fascicle, inferior longitudinal fascicle, arcuate fibers, commissural fibers, corticothalamic fibers, and frontooccipital fascicle) in all 37 patients. Using the cubic ROIs-based protocol, 39.9% of these language-related fiber tracts were detected in the examined patients, as opposed to 76.0% when performing nTMS-based DTI FT. For specifically tracking the arcuate fascicle, however, the cubic ROIs-based approach showed better results (97.3% vs 75.7% with nTMS-based DTI FT). CONCLUSIONS The cubic ROIs-based protocol was designed for arcuate fascicle tractography, and this study shows that it is still useful for this intention. However, superior results were obtained using the nTMS-based DTI FT for visualization of other language-related fiber tracts.

Feasibility of nTMS-based DTI fiber tracking of language pathways in neurosurgical patients using a fractional anisotropy threshold.

BACKGROUND: Navigated transcranial magnetic stimulation (nTMS) provides language maps in brain tumor patients. Yet, corresponding data on the visualization of language-related subcortical pathways is lacking. Therefore, this study evaluates the feasibility of nTMS-based diffusion tensor imaging fiber tracking (DTI FT) for subcortical language pathways by a fractional anisotropy (FA) protocol. NEW METHOD: DTI FT was performed in 37 patients suffering from left-sided perisylvian brain lesions based on nTMS data exclusively, using the FA-based protocol originally established for the corticospinal tract (CST) by Frey et al. (2012): minimum fiber length was 110mm and the highest individual FA value leading to visualization of white matter tracts was determined as the FA threshold (FAT). Then, deterministic DTI FT using an FA value of 100%, 75%, 50%, and 25% of the individual FAT (with 25% as an additional setting to the original protocol) was performed. RESULTS: Our approach visualized 9 language-related subcortical white matter pathways. By using 100% FAT, the mean percentage of visualized tracts was 13.5%, whereas DTI FT performed with 75%, 50%, and 25% FAT detected 30.6%, 61.3%, and 93.7% of language-related fiber tracts, respectively. COMPARISON WITH EXISTING METHODS: nTMS language mapping alone is not able to visualize subcortical language-related pathways. CONCLUSIONS: This study shows that nTMS language maps are feasible for DTI FT of language-related pathways within the scope of a FAT-based protocol. Although this approach is novel and might be helpful during scientific neuroimaging and tumor resection, intraoperative validation is needed to go beyond the level of feasibility.

Preoperative language mapping by repetitive navigated transcranial magnetic stimulation and diffusion tensor imaging fiber tracking and their comparison to intraoperative stimulation.

INTRODUCTION: Repetitive navigated transcranial magnetic stimulation (rTMS) can be used for preoperative language mapping, but it still suffers from comparatively high sensitivity and low specificity when compared to direct cortical stimulation (DCS). Therefore, this study evaluates whether the additional consideration of rTMS-based diffusion tensor imaging fiber tracking (DTI FT) for identifying language-positive brain regions improves specificity when compared to DCS. METHODS: We performed rTMS, rTMS-based DTI FT, and DCS during awake surgery combined with object naming in 20 patients suffering from left-sided perisylvian brain lesions. For rTMS, different error rate thresholds (ERTs) and error types were considered, and DTI FT was conducted with individualized fractional anisotropy thresholds (FATs). Then, receiver operating characteristics (ROC) for rTMS vs. DCS, rTMS-based DTI FT vs. DCS, and rTMS spots confirmed by rTMS-based DTI FT vs. DCS were calculated. RESULTS: In general, rTMS vs. DCS was in good accordance with previous literature (sensitivity/specificity: 92.7/13.3 % for all naming errors without ERT). In addition, rTMS-based DTI FT vs. DCS led to balanced results when tracking was based on all errors as well (sensitivity/specificity: 62.8/64.3 % for 100 % FAT). However, rTMS combined with rTMS-based DTI FT vs. DCS did not lead to any improvement in specificity when compared to rTMS vs. DCS alone. CONCLUSION: The additional use of rTMS-based DTI FT to rTMS did not improve the identification of DCS-positive language areas during awake surgery. Yet, concerning rTMS-based DTI FT, this new technique must be validated itself by intraoperative subcortical stimulation.

Motor areas of the frontal cortex in patients with motor eloquent brain lesions.

OBJECTIVE Because of its huge clinical potential, the importance of premotor areas for motor function itself and plastic reshaping due to tumors or ischemic brain lesions has received increased attention. Thus, in this study the authors used navigated transcranial magnetic stimulation (nTMS) to investigate whether tumorous brain lesions induce a change in motor cortex localization in the human brain. METHODS Between 2010 and 2013, nTMS motor mapping was performed in a prospective cohort of 100 patients with brain tumors in or adjacent to the rolandic cortex. Spatial data analysis was performed by normalization of the individual motor maps and creation of overlays according to tumor location. Analysis of motor evoked potential (MEP) latencies was performed regarding mean overall latencies and potentially polysynaptic latencies, defined as latencies longer than 1 SD above the mean value. Hemispheric dominance, lesion location, and motor-function deficits were also considered. RESULTS Graphical analysis showed that motor areas were not restricted to the precentral gyrus. Instead, they spread widely in the anterior-posterior direction. An analysis of MEP latency showed that mean MEP latencies were shortest in the precentral gyrus and longest in the superior and middle frontal gyri. The percentage of latencies longer than 1 SD differed widely across gyri. The dominant hemisphere showed a greater number of longer latencies than the nondominant hemisphere (p < 0.0001). Moreover, tumor location-dependent changes in distribution of polysynaptic latencies were observed (p = 0.0002). Motor-function deficit did not show any statistically significant effect. CONCLUSIONS The distribution of primary and polysynaptic motor areas changes in patients with brain tumors and highly depends on tumor location. Thus, these data should be considered for resection planning.

Correlating subcortical interhemispheric connectivity and cortical hemispheric dominance in brain tumor patients: A repetitive navigated transcranial magnetic stimulation study.

OBJECTIVE: The present study aims to investigate the relationship between transcallosal interhemispheric connectivity (IC) and hemispheric language lateralization by using a novel approach including repetitive navigated transcranial magnetic stimulation (rTMS), hemispheric dominance ratio (HDR) calculation, and rTMS-based diffusion tensor imaging fiber tracking (DTI FT). METHODS: 31 patients with left-sided perisylvian brain lesions underwent diffusion tensor imaging (DTI) and rTMS language mapping. Cortical language-positive rTMS spots were used to calculate HDRs (HDR: quotient of the left-sided divided by right-sided naming error rates for corresponding left- and right-sided cortical regions) and to create regions of interest (ROIs) for DTI FT. Then, fibers connecting the rTMS-based ROIs of both hemispheres were tracked, and the correlation of IC to HDRs was calculated via Spearman's rank correlation coefficient (rs). RESULTS: Fibers connecting rTMS-based ROIs of both hemispheres were detected in 12 patients (38.7%). Within the patients in which IC was detected, the mean number of subcortical IC fibers ± standard deviation (SD) was 138.0 ± 346.5 (median: 7.5; range: 1-1,217 fibers). Regarding rs for the correlation of HDRs and fiber numbers of patients that showed IC, only moderate correlation was revealed. CONCLUSION: Our approach might be beneficial and technically feasible for further investigation of the relationship between IC and language lateralization. However, only moderate correlation was revealed in the present study.

Non-invasive mapping of calculation function by repetitive navigated transcranial magnetic stimulation.

Concerning calculation function, studies have already reported on localizing computational function in patients and volunteers by functional magnetic resonance imaging and transcranial magnetic stimulation. However, the development of accurate repetitive navigated TMS (rTMS) with a considerably higher spatial resolution opens a new field in cognitive neuroscience. This study was therefore designed to evaluate the feasibility of rTMS for locating cortical calculation function in healthy volunteers, and to establish this technique for future scientific applications as well as preoperative mapping in brain tumor patients. Twenty healthy subjects underwent rTMS calculation mapping using 5 Hz/10 pulses. Fifty-two previously determined cortical spots of the whole hemispheres were stimulated on both sides. The subjects were instructed to perform the calculation task composed of 80 simple arithmetic operations while rTMS pulses were applied. The highest error rate (80 %) for all errors of all subjects was observed in the right ventral precentral gyrus. Concerning division task, a 45 % error rate was achieved in the left middle frontal gyrus. The subtraction task showed its highest error rate (40 %) in the right angular gyrus (anG). In the addition task a 35 % error rate was observed in the left anterior superior temporal gyrus. Lastly, the multiplication task induced a maximum error rate of 30 % in the left anG. rTMS seems feasible as a way to locate cortical calculation function. Besides language function, the cortical localizations are well in accordance with the current literature for other modalities or lesion studies.

Impairment of preoperative language mapping by lesion location: a functional magnetic resonance imaging, navigated transcranial magnetic stimulation, and direct cortical stimulation study.

OBJECT: Language mapping by repetitive navigated transcranial magnetic stimulation (rTMS) is increasingly used and has already replaced functional MRI (fMRI) in some institutions for preoperative mapping of neurosurgical patients. Yet some factors affect the concordance of both methods with direct cortical stimulation (DCS), most likely by lesions affecting cortical oxygenation levels. Therefore, the impairment of the accuracy of rTMS and fMRI was analyzed and compared with DCS during awake surgery in patients with intraparenchymal lesions. METHODS: Language mapping was performed by DCS, rTMS, and fMRI using an object-naming task in 27 patients with left-sided perisylvian lesions, and the induced language errors of each method were assigned to the cortical parcellation system. Subsequently, the receiver operating characteristics were calculated for rTMS and fMRI and compared with DCS as ground truth for regions with (w/) and without (w/o) the lesion in the mapped regions. RESULTS: The w/ subgroup revealed a sensitivity of 100% (w/o 100%), a specificity of 8% (w/o 5%), a positive predictive value of 34% (w/o: 53%), and a negative predictive value (NPV) of 100% (w/o: 100%) for the comparison of rTMS versus DCS. Findings for the comparison of fMRI versus DCS within the w/ subgroup revealed a sensitivity of 32% (w/o: 62%), a specificity of 88% (w/o: 60%), a positive predictive value of 56% (w/o: 62%), and a NPV of 73% (w/o: 60%). CONCLUSIONS: Although strengths and weaknesses exist for both rTMS and fMRI, the results show that rTMS is less affected by a brain lesion than fMRI, especially when performing mapping of language-negative cortical regions based on sensitivity and NPV.