Left Hemisphere Tumors Research Articles

Tumors Affect the Metabolic Connectivity of the Human Brain Measured by 18 F-FDG PET.

18 F-FDG PET captures the relationship between glucose metabolism and synaptic activity, allowing for modeling brain function through metabolic connectivity. We investigated tumor-induced modifications of brain metabolic connectivity. Forty-three patients with left hemispheric tumors and 18 F-FDG PET/MRI were retrospectively recruited. We included 37 healthy controls (HCs) from the database CERMEP-IDB-MRXFDG. We analyzed the whole brain and right versus left hemispheres connectivity in patients and HC, frontal versus temporal tumors, active tumors versus radiation necrosis, and patients with high Karnofsky performance score (KPS = 100) versus low KPS (KPS < 70). Results were compared with 2-sided t test ( P < 0.05). Twenty high-grade glioma, 4 low-grade glioma, and 19 metastases were included. The patients' whole-brain network displayed lower connectivity metrics compared with HC ( P < 0.001), except assortativity and betweenness centrality ( P = 0.001). The patients' left hemispheres showed decreased similarity, and lower connectivity metrics compared with the right ( P < 0.01), with the exception of betweenness centrality ( P = 0.002). HC did not show significant hemispheric differences. Frontal tumors showed higher connectivity metrics ( P < 0.001) than temporal tumors, but lower betweenness centrality ( P = 4.5 -7 ). Patients with high KPS showed higher distance local efficiency ( P = 0.01), rich club coefficient ( P = 0.0048), clustering coefficient ( P = 0.00032), betweenness centrality ( P = 0.008), and similarity ( P = 0.0027) compared with low KPS. Patients with active tumor(s) (14/43) demonstrated significantly lower connectivity metrics compared with necroses. Tumors cause reorganization of metabolic brain networks, characterized by formation of new connections and decreased centrality. Patients with frontal tumors retained a more efficient, centralized, and segregated network than patients with temporal tumors. Stronger metabolic connectivity was associated with higher KPS.

Preserved White Matter Integrity and Recovery After Brain Tumor Surgery: A Prospective Pilot Study on the Frontal Aslant Tract.

Introduction: Damage to white matter tracts can cause severe neurological deficits, which are often hardly predictable before brain tumor surgery. To explore the possibility of assessing white matter integrity and its preservation, we chose the frontal aslant tract (FAT) due to its involvement in multiple neurological functions such as speech and movement initiation. Methods: Right-handed patients with left hemispheric intracerebral tumors underwent FAT tractography within 7 days before and 3 days after surgery. Neurological performance score and aphasia score were assessed within 7 days before and after surgery, as well as at follow-up 3 months postoperatively. Results: Fifteen patients were prospectively analyzed. After multivariate analysis and receiver operating characteristic analysis, we found that preoperative fractional anisotropy (FA) of the left FAT indicated the preoperative aphasia score (cutoff 0.40, p = 0.015). Aphasia scores 3 months postoperatively were predicted by both postoperative FA of the left FAT (cutoff 0.35, p = 0.005) and postoperatively preserved FA of the left FAT (cutoff 95.8%, p = 0.017). Postoperatively preserved right FAT FA inversely predicted postoperative aphasia score (cutoff 95.1%, p = 0.016). Discussion: Assessment of white matter integrity preservation is possible and correlates with outcome after brain tumor surgery. It may be useful for patient counseling and assessment of rehabilitation potential, as well as to investigate relevant brain networks in the future. Clinical Trial Registration: The trial was prospectively registered at ClinicalTrials.gov (NCT04302857).

Relationships between reading performance and regional spontaneous brain activity following surgical removal of primary left-hemisphere tumors: A resting-state fMRI study

Left-hemisphere intraparenchymal primary brain tumor patients are at risk of developing reading difficulties that may be stable, improve or deteriorate after surgery. Previous studies examining language organization in brain tumor patients have provided insights into neural plasticity supporting recovery. Only a single study, however, has examined the role of white matter tracts in preserving reading ability post-surgery and none have examined the functional reading network. The current study aimed to investigate the regional spontaneous brain activity associated with reading performance in a group of 36 adult patients 6–24 months following left-hemisphere tumor resection. Spontaneous brain activity was assessed using resting-state fMRI (rs-fMRI) regional homogeneity (ReHo) and fractional amplitude low frequency fluctuation (fALFF) metrics, which measure local functional connectivity and activity, respectively. ReHo in the left occipito-temporal and right superior parietal regions was negatively correlated with reading performance. fALFF in the putamen bilaterally and the left cerebellum was negatively correlated with reading performance, and positively correlated in the right superior parietal gyrus. These findings are broadly consistent with reading networks reported in healthy participants, indicating that reading ability following brain tumor surgery might not involve substantial functional re-organization.

Effect of tumor genetics, pathology, and location on fMRI of language reorganization in brain tumor patients

ObjectivesLanguage reorganization may follow tumor invasion of the dominant hemisphere. Tumor location, grade, and genetics influence the communication between eloquent areas and tumor growth dynamics, which are drivers of language plasticity. We evaluated tumor-induced language reorganization studying the relationship of fMRI language laterality to tumor-related variables (grade, genetics, location), and patient-related variables (age, sex, handedness).MethodsThe study was retrospective cross-sectional. We included patients with left-hemispheric tumors (study group) and right-hemispheric tumors (controls). We calculated five fMRI laterality indexes (LI): hemispheric, temporal lobe, frontal lobe, Broca’s area (BA), Wernicke’s area (WA). We defined LI ≥ 0.2 as left-lateralized (LL) and LI < 0.2 as atypical lateralized (AL). Chi-square test (p < 0.05) was employed to identify the relationship between LI and tumor/patient variables in the study group. For those variables having significant results, confounding factors were evaluated in a multinomial logistic regression model.ResultsWe included 405 patients (235 M, mean age: 51 years old) and 49 controls (36 M, mean age: 51 years old). Contralateral language reorganization was more common in patients than controls. The statistical analysis demonstrated significant association between BA LI and patient sex (p = 0.005); frontal LI, BA LI, and tumor location in BA (p < 0.001); hemispheric LI and fibroblast growth factor receptor (FGFR) mutation (p = 0.019); WA LI and O6-methylguanine-DNA methyltransferase promoter (MGMT) methylation in high-grade gliomas (p = 0.016).ConclusionsTumor genetics, pathology, and location influence language laterality, possibly due to cortical plasticity. Increased fMRI activation in the right hemisphere was seen in patients with tumors in the frontal lobe, BA and WA, FGFR mutation, and MGMT promoter methylation.Key Points• Patients harboring left-hemispheric tumors present with contralateral translocation of language function. Influential variables for this phenomenon included frontal tumor location, BA location, WA location, sex, MGMT promoter methylation, and FGFR mutation.• Tumor location, grade, and genetics may influence language plasticity, thereby affecting both communication between eloquent areas and tumor growth dynamics.• In this retrospective cross-sectional study, we evaluated language reorganization in 405 brain tumor patients by studying the relationship of fMRI language laterality to tumor-related variables (grade, genetics, location), and patient-related variables (age, sex, handedness).

Brain Lesions Associated with Communication-Related Quality of Life Following Surgical Removal of Primary Left-Hemisphere Tumours

ABSTRACT Background Long-term health-related quality of life (HRQoL) is an important consideration in planning treatment for individuals with brain tumours. Aim The current study examined relationships between HRQoL and anatomical location of the lesion in patients 6-24 months post-surgery. Methods Following left-hemisphere tumour resection, 37 individuals underwent behavioural testing and MRI. A principal component analysis across 10 HRQoL measures identified two components explaining ~62% of the variance: a communication-related and a mood-related component. Three lesion maps were generated per participant capturing (1) the primary resection, (2) the resection plus residual tumour, oedema, and peri-resection treatment effect (resection+), and (3) residual tumour, oedema, and peri-resection treatment effect alone (residual). Relationships between HRQoL components and lesion maps were examined using voxel-wise lesion symptom-mapping as well as general linear models predicting tract- and voxel-wise disconnection severities. Results Communication-related quality of life was significantly associated with lesions comprising both the resection+ and residual tumour in the left medial inferior parietal lobe. Voxel-wise analyses of white matter disconnection severities revealed significant associations between communication-related quality of life and thalamostriatal fibres for the residual tumour lesions. None of the analyses involving mood-related quality of life or the primary resection lesion maps were significant. Conclusions The findings highlight the role of the residual tumour, oedema, and peri-resection treatment effects and associated white matter disconnection in communication-related quality of life following treatment.

NIMG-14. RESTING STATE EXECUTIVE CONTROL AND SALIENCE NETWORK CONNECTIVITY IN CLINICALLY STABLE LOWER GRADE GLIOMA COVARIES WITH COGNITIVE PERFORMANCE

Abstract BACKGROUND Survival outcomes for patients with lower grade gliomas (LrGG) are improving. However, injury from tumor growth and consequences of treatment often leads to impaired cognition, particularly in cognitive domains reliant on distributed functional networks and intact white-matter tracts. Resting state functional MRI (rsfMRI) is a method of investigating the integrity of these functional networks. METHODS This study investigated rsfMRI connectivity in 21 patients with clinically stable LrGG compared to age- and gender-matched healthy controls, and associated imaging measures with cognitive outcomes. Data were acquired for 12 cognitive tests administered within one week of imaging. RsfMRI and T1-weighted images for 21 research controls were acquired from OpenNeuro datasets. RsfMRI data were processed and analyzed using the CONN toolbox using CONN’s standard regions of interest (ROI) for the 8 canonical networks as seeds, and cognitive test scores as covariates, with a threshold for T tests of p&amp;lt; .001 uncorrected. RESULTS Median age was 48 years old (range 27-67). There were 6 astrocytomas, IDHmut; 3 astrocytomas IDH-wt, 8 oligodendrogliomas, and 4 NOS. Thirteen had left hemisphere tumors (8 frontal, 3 parietal, 2 temporal), and 6 right (5 frontal, 1 temporal). Fourteen had previously recieved radiotherapy. There was significantly lower connectivity in frontoparietal executive control and the salience networks in LrGG patients versus controls. Within patients, lower executive control network connectivity covaried with worse performance on executive measures (FAS, Tower of London, Trails-A, Animal Naming, FrSBe), and attention and working memory measures (Digit Symbol, HVLT). Lower salience network connectivity covaried with poorer performance on executive measures (FrSBe, FAS) and attention and working memory measures (Digit Span, HVLT, WAIS-WM). CONCLUSION In clinically stable LrGG, rsfMRI measures of network connectivity are potentially useful markers to monitor and track, given the concordance with cognition, and could help guide cognitive assessment and rehabilitation.

OS07.5A Diagnostic Instrument for Mild Aphasia (DIMA): sensitive and valuable addition to standard language assessment in glioma patients

Abstract BACKGROUND Low-grade glioma (LGG) patients typically suffer from mild aphasia that often cannot be detected with standard aphasia tests. The Diagnostic Instrument for Mild Aphasia (DIMA) is the first standardized test-battery to assess mild language disorders. We investigate pre- and postoperative linguistic abilities of LGG and high-grade glioma (HGG) patients with the DIMA. METHODS The DIMA consists of subtests that tap phonology (word, compound, non-word, sentence repetition), semantics (odd-picture-out), and syntax (sentence completion). Additionally, we administered the Boston Naming Test, Category- and Letter Fluency, and the Token Test. Patients were assessed before awake surgery (T1, N=98), three-months (T2, N=69), and one-year (T3, N=30) postoperatively. DIMA performance was compared to healthy controls (N=214). Group differences were examined with parametric (t-test) and nonparametric (Mann-Whitney-U, Wilcoxon) tests. RESULTS DIMA: Preoperatively, patients deviated on sentence repetition and sentence completion (p&amp;lt;0.05). HGG patients performed worse than LGG on word, non-word, and sentence repetition (p&amp;lt;0.05). There was no effect of hemispheric tumor localization. At T2, compound repetition and odd-picture-out also became impaired (p&amp;lt;0.05) and there was a decline compared to T1 on all repetition tasks (p&amp;lt;0.05). At T3, only sentence completion remained impaired (p&amp;lt;0.01) with a deterioration compared to T1 (p&amp;lt;0.01). Standard tests: At T1, patients were impaired on BNT, Category- and Letter Fluency (p&amp;lt;0.01). HGG patients performed worse than LGG patients on BNT and TT (p&amp;lt;0.01). Patients with left-hemispheric tumors performed worse on BNT and Letter Fluency compared to right-hemispheric tumors (p&amp;lt;0.05). At T2, TT also became impaired (p&amp;lt;0.05) and patients declined compared to T1 on Verbal Fluency tests (p&amp;lt;0.01). At T3, only BNT and Category Fluency remained impaired (p&amp;lt;0.05), with no significant declines compared to T1. CONCLUSION The DIMA is the first test-battery to detect peri-operative impairments at different linguistic levels (phonology, semantics, syntax) in patients with left- or right-hemispheric gliomas. It even appeared more sensitive to detect surgical effects than standard tests: all phonological DIMA subtests captured short-term decline (T1-T2), in line with earlier evidence for the value of (non-)word repetition. DIMA sentence completion detected long-term decline (T1-T3), reflecting earlier spontaneous speech analyses. As expected, Verbal Fluency was also sensitive to short-term postoperative decline. Left-hemispheric tumor localization only affected standard test performance. HGG patients had more severe impairments than LGG on DIMA repetition and standard tests (BNT and TT). We advise adding the DIMA to standard language evaluation of glioma patients, as it allows for more detailed counseling about language outcome.

Tumor location and reduction in functional MRI estimates of language laterality.

OBJECTIVEBrain tumors located close to the language cortex may distort functional MRI (fMRI)–based estimates of language dominance. The nature of this distortion, and whether this is an artifact of numerous confounders, remains unknown. The authors hypothesized tumor bias based on laterality estimates independent of confounders and that the effects are the greatest for tumors proximal to Broca’s area.METHODSTo answer this question, the authors reviewed more than 1113 patients who underwent preoperative fMRI to match samples on 11 known confounders (tumor location, size, type, and grade; seizure history; prior neurosurgery; aphasia presence and severity; and patient age, sex, and handedness). The samples included 30 patients with left hemisphere tumors (15 anterior and 15 posterior) and 30 with right hemisphere tumors (15 anterior and 15 posterior), thus totaling 60 patients (25 women; 18 left-handed and 4 ambidextrous; mean age 47 [SD 14.1] years). Importantly, the authors matched not only patients with left and right hemisphere tumors but also those with anterior and posterior tumors. Standard fMRI laterality indices (LIs) were calculated using whole-brain and region of interest (ROI) approaches (Broca’s and Wernicke’s areas).RESULTSTumors close to Broca’s area in the left hemisphere decreased LIs independently of known confounders. At the whole-brain level, this appeared to reflect a decrease in LI values in patients with left anterior tumors compared with patients with right anterior tumors. ROI analysis replicated these findings. Broca’s area LIs were significantly lower (p = 0.02) in patients with left anterior tumors (mean LI 0.28) when compared with patients with right anterior tumors (mean LI 0.70). Changes in Wernicke’s area–based LIs did not differ as a function of the tumor hemisphere. Therefore, in patients with left anterior tumors, it is essential to assess language laterality using left posterior ROIs. In all remaining tumor groups (left posterior tumors and right hemisphere tumors), language laterality derived from the anterior language ROI was the most robust measure of language dominance.CONCLUSIONSPatients with tumors close to Broca’s area showed more bilateral fMRI language maps independent of known confounders. The authors caution against the assumption that this reduced language laterality suggests no or little risk to language function following tumor resection in the left inferior frontal gyrus. Their results address how to interpret fMRI data for neurosurgical purposes, along with theoretical questions of contralesional functional compensation and disinhibition.

A-094 Isocitrate Dehydrogenase Status and Cognition in Glioma Patients

Abstract Objective In gliomas, isocitrate dehydrogenase-wildtype (IDH-wt) is associated with poorer prognosis and is correlated with lower brain connectivity, implicating cognitive impairment. Little is known about the impact of IDH-wt on cognition. This study aimed to explore the relationship between IDH-wt and cognition. Method Thirty-eight patients (Age M = 48.73 ± 14.98; 50% female) diagnosed with a glioma (29% grade II, 16% grade III, 21% grade IV; Karnofsky Performance Status score (KPS) M = 88.75 ± 14.24) were selected from a retrospective data cohort. 34.2% of patients had left hemisphere tumors, 34.2% of tumors were in the frontal lobes, and 15.8% were temporal lobe tumors. Patients were assessed via abbreviated neuropsychological battery following surgical resection prior to radiation and/or chemotherapy. Results The overall cognitive composite was not statistically significant via independent samples t-test (IDH-wt+: M = 42.37; IDH-wt-: M = 39.29; p = 0.897). Subdomains for attention/executive functioning (p = 0.625), memory (p = 0.923), and language (p = 0.501) were not significantly different. Logistic regression was conducted to investigate how IDH status predicts cognitive status. The coefficient has a Wald statistic equal to 0.042 which is not significant (critical value of 0.837) [df = 1]. Of those with IDH-wt+, 57% were impaired and 43% remained intact. Conclusion We did not find a significant association between IDH status and cognition though sample size is a significant limitation of the present study. More investigations are needed given it is possible that cognitive performance is related to IDH status and knowledge in this area could improve patient care/patient education.

Preoperative transcranial magnetic stimulation for picture naming is reliable in mapping segments of the arcuate fasciculus.

In preoperative planning for neurosurgery, both anatomical (diffusion imaging tractography) and functional tools (MR-navigated transcranial magnetic stimulation) are increasingly used to identify and preserve eloquent language structures specific to individuals. Using these tools in healthy adults shows that speech production errors occur mainly in perisylvian cortical sites that correspond to subject-specific terminations of the major language pathway, the arcuate fasciculus. It is not clear whether this correspondence remains in oncological patients with altered tissue. We studied a heterogeneous cohort of 30 patients (fourteen male, mean age 44), undergoing a first or second surgery for a left hemisphere brain tumour in a language-eloquent region, to test whether speech production errors induced by preoperative transcranial magnetic stimulation had consistent anatomical correspondence to the arcuate fasciculus. We used navigated repetitive transcranial magnetic stimulation during picture naming and recorded different perisylvian sites where transient interference to speech production occurred. Spherical deconvolution diffusion imaging tractography was performed to map the direct fronto-temporal and indirect (fronto-parietal and parieto-temporal) segments of the arcuate fasciculus in each patient. Speech production errors were reported in all patients when stimulating the frontal lobe, and in over 90% of patients in the parietal lobe. Errors were less frequent in the temporal lobe (54%). In all patients, at least one error site corresponded to a termination of the arcuate fasciculus, particularly in the frontal and parietal lobes, despite distorted anatomy due to a lesion and/or previous resection. Our results indicate that there is strong correspondence between terminations of the arcuate fasciculus and speech errors. This indicates that white matter anatomy may be a robust marker for identifying functionally eloquent cortex, particularly in the frontal and parietal lobe. This knowledge may improve targets for preoperative mapping of language in the neurosurgical setting.

BT-05 A CASE OF GLIOMATOSIS CEREBRI WITH TOTAL SPINAL CORD EXTENSION

INTRODUCTIONAlthough gliomatosis cerebri is no longer a pathological diagnostic name, it is still an important disease state as a gliomatosis cerebri growth pattern. Here we report a case of gliomatosis cerebri originating from the left cerebral hemisphere that developed whole spinal cord.CASEA 10-year-old boy. He has a history of 13q-syndrome and left retinoblastoma. Left eye enucleation and chemotherapy (modified 98A1) have been performed. MRI in July 2017 showed no abnormalities, but in September 2018, he developed epilepsy. MRI revealed a gliomatosis cerebri that spreads extensively in the left cerebral hemisphere. Biopsy revealed anaplastic astrocytoma (MIB-1 LI; 22%, IDH1 / 2; WT, TERT C228T mutation positive) and IMRT (59.4Gy) and temozolomide (Stupp regimen) were performed in December 2018. In June 2019, neck pain developed. Head and neck MRI revealed that the tumor in the head increased lightly, and there was no suspicion of tumor growth in the brainstem, but the tumor progressed to the entire spinal cord. Therefore, radiation therapy was started from the lower brainstem that had not been irradiated last time to the entire spinal cord, and administration of bevacizumab was started.DISCUSSIONBased on the single cell origin theory, the left hemisphere tumor and spinal cord tumor should be continuous. Since gliomatosis cerebri is visualized on MRI only after the tumor volume has increased and edema has occurred, it may appear as if there is no tumor in between. The spinal cord MRI was not taken, so it is only speculation, but it seems that tumor cells had probably infiltrated the spinal cord from the beginning, and it seems that it gradually increased because it was not irradiated. Considering the possibility of remote invasion as in this case, it is necessary to consider taking MRI of spinal cord at the first occurrence.

NIMG-64. IMPACT OF TUMOR LOCATION ON IMAGE-DERIVED VOLUME, PROLIFERATION RATE AND GROWTH VELOCITY IN GLIOBLASTOMA PATIENTS

Abstract INTRODUCTION Glioblastoma (GBM) is the most common malignant primary brain tumor in adults with a median overall survival (OS) of 15months. Despite advancements in treatments, prognosis is dismal and the prognostic significance of tumor location is not entirely understood. METHODOLOGY: In our study, we investigated sex-specific volumetric, tumor growth kinetics, and outcome differences among GBMs in various brain locations. Primary GBM patients with pretreatment magnetic resonance imaging (MRI) data (N=289, 173 males, 116 females) were selected from our brain tumor repository. Tumor abnormality was segmented on T1-weighted post-gadolinium contrast agent (T1Gd) MRIs. We utilized the Harvard-Oxford brain atlases to determine the location of GBMs. RESULTS Overall, our study found smaller tumors in the left hemisphere. This may be expected as left-hemispheric GBM symptoms could present earlier, leading to earlier diagnosis and treatment. However, when the cohort was split by sex, we found this observation significant for females only in the parietal lobe (p &lt; 0.0001). Further, female GBMs demonstrated smaller necrotic volume in the left hemisphere (p = 0.030). Sex-specific differences in incidence were noted in the temporal and occipital lobes (2M:1F). Comparing tumor growth kinetics in different brain locations and hemispheres, females had significantly lower tumor proliferation rates in the left hemisphere (p = 0.009) and lower tumor proliferation rates in the left frontal lobe (p = 0.031). Controlling for treatment, patients with frontal lobe tumors had significantly longer OS compared to those with GBMs in the temporal lobe (p = 0.046, 312 days). Differences in growth velocities were noted between frontal and parietal lobe with frontal GBMs having lower velocities in comparison to parietal lobe GBMs. CONCLUSION Together, our results demonstrate that tumor growth and proliferation rates may vary based on location and sex. Additional research is needed to further explore the clinical significance of tumor location.

Whole brain tractography in Malaysian patients using DMRI

Language processing involves multiple brain regions in a predominantly left lateralised cortical network. Language networks however are still very much elusive due to complexity of brain activity profiles that may vary considerably among different individuals particularly when there is a tumour present in the network. The ability to delineate fibres accurately is fundamental in the treatment planning of tumour patients. Tractography is useful in mapping white matter networks, however numerous methods like deterministic, probabilistic and global exist, each presenting with advantages and limitations. This study thus aims to investigate and map structural networks in patients with a left hemisphere primary brain tumour and healthy subjects using dMRI and tractography, with the intent of comparing these three methods. In this study, retrospective Hospital USM radiological 3T MRI treatment planning data between September 2012 and December 2017 of 6 left hemisphere tumour patients (3 gliomas, 3 meningiomas) and 3 radiologically normal brain patients is being used. Manual processing and packages DSI Studio, MRtrix3, ITK and FSL were used for pre-processing the data, setting up ROIs and running the different methods of tractography analysis. Fibre length and coefficient data were statistically compared using SPSS. The results indicated that probabilistic algorithms delineated the selected networks better than deterministic. Global tractography yielded slightly better results however in the case of tumour patients some false positives were indicated. Deterministic analysis terminated prematurely in line with previous research. Local probabilistic seems to yield more applicable as previous research has indicated in the case of other pathology.

Intraoperative electrostimulation for awake brain mapping: how many positive interference responses are required for reliability?

The purpose of this study was to characterize the reproducibility of language trials within and between brain mapping sessions. Brain mapping and baseline testing data from 200 adult patients who underwent resection of left-hemisphere tumors were evaluated. Data from 11 additional patients who underwent a second resection for recurrence were analyzed separately to investigate reproducibility over time. In all cases, a specific protocol of electrostimulation brain mapping with a controlled naming task was used to detect language areas, and the results were statistically compared with preoperative and intraoperative baseline naming error rates. All patients had normal preoperative error rates, controlled for educational level and age (mean 8.92%, range 0%-16.25%). Intraoperative baseline error rates within the normal range were highly correlated with preoperative ones (r = 0.74, p < 10-10), although intraoperative rates were usually higher (mean 13.30%, range 0%-26.67%). Initially, 3 electrostimulation trials were performed in each cortical area. If 2 of 3 trials showed language interference, 1 or 2 additional trials were performed (depending on results). In the main group of 200 patients, there were 82 single interferences (i.e., positive results in 1 of 3 trials), 227 double interferences (2/3), and 312 full interferences (3/3). Binomial statistics revealed that full interferences were statistically significant (vs intraoperative baseline) in 92.7% of patients, while double interferences were significant only in 38.5% of patients, those with the lowest error rates. On further testing, one-third of the 2/3 trials became 2/4 trials, which was significant in only one-quarter of patients. Double interference could be considered significant for most patients (> 90%) when confirmed by 2 subsequent positive trials (4/5). In the 11 patients who were operated on twice, only 26% of areas that tested positive in the initial operation tested positive in the second and showed the same type of interference and the same current threshold (i.e., met all 3 criteria). Electrostimulation trials in awake brain mapping produced graded patterns of positive reproducibility levels, and their significance varied with the baseline error rates. The results suggest that caution is warranted when 2 of 3 trials are positive, although the need for additional trials depends on the individual patients' baseline error rates. Reproducibility issues should be considered in the interpretation of data from awake brain mapping.

Functional Connectivity in Adult Brain Tumor Patients: A Systematic Review.

Brain tumor (BT) patients often experience reduced cognitive abilities and disrupted adaptive functioning before and after treatment. An innovative approach to understanding the underlying brain networks associated with these outcomes has been to study the brain's functional connectivity (FC), the spatially distributed and temporally correlated activity throughout the brain, and how it can be affected by a tumor. The present review synthesized the extant BT FC literature that utilizes functional magnetic resonance imaging to study FC strength of commonly observed networks during rest and task. A systematic review of English articles using PubMed was conducted. Search terms included brain tumor OR glioma AND functional connectivity, independent component analysis, ICA, psychophysiological interaction, OR PPI. Studies in which participants were diagnosed with BTs as adults that evaluated specific networks of interest using independent component analysis or seed-based component analysis were included. Twenty-five studies met inclusion criteria. BT patients often presented with decreases in FC strength within well-established networks and increases in atypical FC patterns. Network differences were tumor adjacent and distal, and left hemisphere tumors generally had a greater impact on FC. FC alterations often correlated with behavioral or cognitive outcomes when assessed. Overall, BTs appear to lead to various alterations in FC across different functional networks, and the most common change is a decrease in expected FC strength. More longitudinal studies are needed to determine the time course of network alterations across treatment and recovery, the role of medical treatments in BT survivors' FC, and the potential of FC patterns as biomarkers of cognitive outcomes.

Impact of Laterality on Surgical Outcome of Glioblastoma Patients: A Retrospective Single-Center Study.

Resection of left hemisphere (LH) tumors is often complicated by the risks of causing language dysfunction. Although neurosurgeons' concerns when operating on the presumed dominant hemisphere are well known, literature evaluating laterality as a predictive surgical parameter in glioblastoma (GB) patients is sparse. We evaluated whether tumor laterality correlated with surgical performance, functional outcome, and survival. All patients with GB treated at our institution between 2006 and 2016 were reviewed. Analysis comprised clinical characteristics, extent of resection (EOR), neurologic outcome, and survival in relation to tumor lateralization. Two hundred thirty-five patients were included. Right hemisphere (RH) tumors were larger and more frequently extended into the frontal lobe. Preoperatively, limb paresis was more frequent in RH, whereas language deficits were more frequent in LH tumors (P= 0.0009 and P < 0.0001, respectively). At 6 months after resection, LH patients presented lower Karnofsky Performance Status (KPS) score (P= 0.036). More patients with LH tumors experienced dysphasia (P < 0.0001), and no difference was seen for paresis. Average EOR was comparable, but complete resection was achieved less often in LH tumors (37.7 vs. 64.8%; P= 0.0028). Although overall survival did not differ between groups, progression-free survival was shorter in LH tumors (7.4 vs. 10.1 months; P= 0.0225). Patients with LH tumors had a pronounced KPS score decline and shorter progression-free survival without effects on overall survival. This observation might partially be attributed to a more conservative surgical resection. Further investigation is needed to assess whether systematic use of awake surgery and intraoperative mapping results in increased EOR and improved quality survival of patients with GB.

Language in individuals with left hemisphere tumors: Is spontaneous speech analysis comparable to formal testing?

ABSTRACTBackground: The relationship between spontaneous speech and formal language testing in people with brain tumors (gliomas) has been rarely studied. In clinical practice, formal testing is typically used, while spontaneous speech is less often evaluated quantitatively. However, spontaneous speech is quicker to sample and may be less prone to test/retest effects, making it a potential candidate for assessing language impairments when there is restricted time or when the patient is unable to undertake prolonged testing.Aim: To assess whether quantitative spontaneous speech analysis and formal testing detect comparable language impairments in people with gliomas. Specifically, we addressed (a) whether both measures detected comparable language impairments in our patient sample; and (b) which language levels, assessment times, and spontaneous speech variables were more often impaired in this subject group.Method: Five people with left perisylvian gliomas performed a spontaneous speech task and a formal language assessment. Tests were administered before surgery, within a week after surgery, and seven months after surgery. Performance on spontaneous speech was compared with that of 15 healthy speakers.Results: Language impairments were detected more often with both measures than with either measure independently. Lexical–semantic impairments were more common than phonological and grammatical impairments, and performance was equally impaired across assessment time points. Incomplete sentences and phonological paraphasias were the most common error types.Conclusions: In our sample both spontaneous speech analysis and formal testing detected comparable language impairments. Currently, we suggest that formal testing remains overall the better option, except for cases in which there are restrictions on testing time or the patient is too tired to undergo formal testing. In these cases, spontaneous speech may provide a viable alternative, particularly if automated analysis of spontaneous speech becomes more readily available in the future. These results await replication in a bigger sample and/or other populations.

Loss of Subcortical Language Pathways Correlates with Surgery-Related Aphasia in Patients with Brain Tumor: An Investigation via Repetitive Navigated Transcranial Magnetic Stimulation-Based Diffusion Tensor Imaging Fiber Tracking.

Within language function research, there is a shift of focus from cortical specialization to a more hodotopical view including subcortical fiber tracts in functional and oncologic considerations. Diffusion tensor imaging fiber tracking (DTI FT) is well established to visualize subcortical fiber tracts. Recently, a new technique has been developed using cortical regions mapped via repetitive navigated transcranial magnetic stimulation (rTMS) as seed regions. This study investigates if rTMS-based DTI FT for language pathways is also feasible postoperatively and whether preoperative versus postoperative fiber changes correlate with changes and severity of the patients' aphasia grades. rTMS-based DTI FT was performed preoperatively and postoperatively in 24 patients with left hemispheric perisylvian tumors. Language pathways were analyzed individually preoperatively and postoperatively with 5 different settings of minimum fiber length and fractional anisotropy. Transient aphasia was defined as any new or worse language impairment caused by surgery that resolved within the regular 3-month follow-up interval. Because postoperative aphasia does not allow rTMS language mapping, preoperative rTMS data were used throughout. Patients with transient aphasia postoperatively had a significant reduction in fiber count compared with patients without deficit (321.5 ± 242.8 fibers vs. 518.0 ± 435.2 fibers; P= 0.01). Furthermore, in this patient group, the arcuate fascicle was lost postoperatively twice as often compared with patients with no deficit after surgery (52% vs. 26%; P < 0.01). This study shows that rTMS-based DTI FT is feasible for postoperative examination of language pathways. Moreover, changes in preoperative versus postoperative fibers correlate well with the grade of aphasia.

Mapping nouns and finite verbs in left hemisphere tumors: a direct electrical stimulation study

ABSTRACTNeurosurgical mapping studies with nouns and finite verbs are scarce and subcortical data are nonexistent. We used a new task that uses finite verbs in six Italian-speaking patients with gliomas in the left language-dominant hemisphere. Language-relevant positive areas were detected only with nouns in four patients, with both tasks yet in distinct cortical areas in one patient, and only with finite verbs in another patient. Positive areas and types of errors varied across participants. Finite verbs provide complementary information to nouns, and permit more accurate mapping of language production when nouns are unaffected by electrical stimulation.

Language in individuals with left hemisphere tumors: Is spontaneous speech analysis equally good as formal testing?

Language in individuals with left hemisphere tumors: Is spontaneous speech analysis equally good as formal testing?