Preoperative executive functioning impairments in patients with a meningioma: does a frontal location matter?

Patients with meningiomas frequently exhibit impairments in executive functioning. There are few studies specifically examining the role of frontal meningioma localization in executive functioning impairments. This study examines whether frontally located meningiomas are specifically associated with executive functioning impairments in a large sample of meningioma patients before treatment, using an axis-wise and lobe-based approach to meningioma localization. We retrospectively examined cognitive performances in 353 patients with frontal, frontally-involved and non-frontal meningiomas on a battery of tests including tests of executive functioning. We applied an axis-based approach to meningioma location, in addition to qualitative lobe-based localization. We examined the association between meningioma coordinates on an anterior-posterior axis and continuous cognitive performance scores in univariate correlations and linear regression analyses. We also examined the association between meningioma coordinates on an anterior-posterior axis with cognitive impairments in multivariable logistic regression analyses. Meningioma position on the anterior-posterior axis was only univariately associated with mean performance on the Stroop test Interference ratio and Symbol Digit Coding task. There was no (multivariable) association with impairments on tests of executive or non-executive domains. Increased odds of impairment on executive functioning tasks were associated with left-localization (Verbal Fluency) and larger meningioma volumes (Shifting Attention). We did not find a specific relation between a frontal meningioma location and executive functioning impairments, which may be explained by widespread organization of executive functioning throughout the brain, diffuse cognitive effects of the mass of meningiomas, functional reorganization due to neuroplasticity, or functional involvement of less-anteriorly located frontal areas.

Cognitive brain activity before and after surgery in meningioma patients.

Neuropsychological studies have demonstrated that meningioma patients frequently exhibit cognitive deficits before surgery and show only limited improvement after surgery. Combining neuropsychological with functional imaging measurements can shed more light on the impact of surgery on cognitive brain function. We aimed to evaluate whether surgery affects cognitive brain activity in such a manner that it may mask possible changes in cognitive functioning measured by neuropsychological tests. Twenty-three meningioma patients participated in a fMRI measurement using a verbal working memory task as well as three neuropsychological tests focused on working memory, just before and 3 months after surgery. A region of interest based fMRI analysis was used to examine cognitive brain activity at these timepoints within the central executive network and default mode network. Neuropsychological assessment showed impaired cognitive functioning before as well as 3 months after surgery. Neuropsychological test scores, in-scanner task performance as well as brain activity within the central executive and default mode network were not significantly different between both timepoints. Our results indicate that surgery does not significantly affect cognitive brain activity in meningioma patients the first few months after surgery. Therefore, the lack of cognitive improvement after surgery is not likely the result of compensatory processes in the brain. Cognitive deficits that are already present before surgery appear to be persistent after surgery and a considerable recovery period. Our study shows potential leads that comprehensive cognitive evaluation can be of added value so that cognitive functioning may become a more prominent factor in clinical decision making.

Can structure predict function at individual level in the human connectome?

Several studies predicting Functional Connectivity (FC) from Structural Connectivity (SC) at individual level have been published in recent years, each promising increased performance and utility. We investigated three of these studies, analyzing whether the results truly represent a meaningful individual-level mapping from SC to FC. Using data from the Human Connectome Project shared accross the three studies, we constructed a predictor by averaging FC of training data and analyzed its performance in the same way. In each case, we found that group average FC is an equivalent or better predictor of individual FC than the predictive models in terms of raw prediction performance. Furthermore, we showed that additional analyses performed by the authors of the three studies, in which they attempt to show that their predicted FC has value beyond raw prediction performance, could also be reproduced using the group average FC predictor. This makes it unclear whether any of the three methods represent a meaningful individual-level predictive model. We conclude that either the methods are not appropriate for the data, that the sample size is too small, or that the data does not contain sufficient information to learn a mapping from SC to FC. We advise future individual-level studies to explicitly report results in comparison to the performance of the group average, and carefully demonstrate that their predictions contain meaningful individual-level information. Finally, we believe that investigating alternatives for the construction of SC and FC may improve the chances of developing a meaningful individual-level mapping from SC to FC.

Cognitive functioning in untreated glioma patients: The limited predictive value of clinical variables.

BACKGROUND: Previous research identified many clinical variables that are significantly related to cognitive functioning before surgery. It is not clear whether such variables enable accurate prediction for individual patients' cognitive functioning because statistical significance does not guarantee predictive value. Previous studies did not test how well cognitive functioning can be predicted for (yet) untested patients. Furthermore, previous research is limited in that only linear or rank-based methods with small numbers of variables were used. METHODS: We used various machine learning models to predict preoperative cognitive functioning for 340 patients with glioma across 18 outcome measures. Predictions were made using a comprehensive set of clinical variables as identified from the literature. Model performances and optimized hyperparameters were interpreted. Moreover, Shapley additive explanations were calculated to determine variable importance and explore interaction effects. RESULTS: Best-performing models generally demonstrated above-random performance. Performance, however, was unreliable for 14 out of 18 outcome measures with predictions worse than baseline models for a substantial number of train-test splits. Best-performing models were relatively simple and used most variables for prediction while not relying strongly on any variable. CONCLUSIONS: Preoperative cognitive functioning could not be reliably predicted across cognitive tests using the comprehensive set of clinical variables included in the current study. Our results show that a holistic view of an individual patient likely is necessary to explain differences in cognitive functioning. Moreover, they emphasize the need to collect larger cross-center and multimodal data sets.

Working memory performance in glioma patients is associated with functional connectivity between the right dorsolateral prefrontal cortex and default mode network.

In healthy subjects, activity in the default mode network (DMN) and the frontoparietal network (FPN) has consistently been associated with working memory (WM). In particular, the dorsolateral prefrontal cortex (DLPFC) is important for WM. The functional-anatomical basis of WM impairment in glioma patients is, however, still poorly understood. We investigated whether WM performance of glioma patients is reflected in resting-state functional connectivity (FC) between the DMN and FPN, additionally focusing on the DLPFC. Resting-state functional MRI data were acquired from 45 glioma patients prior to surgery. WM performance was derived from a pre-operative N-back task. Scans were parcellated into ROIs using both the Gordon and Yeo atlas. FC was calculated as the average Pearson correlation between functional time series. The FC between right DLPFC and DMN was inversely related to WM performance for both the Gordon and Yeo atlas (p = .010). No association was found for FC between left DLPFC and DMN, nor between the whole FPN and DMN. The results are robust and not dependent on atlas choice or tumor location, as they hold for both the Gordon and Yeo atlases, and independently of location variables. Our findings show that WM performance of glioma patients can be quantified in terms of interactions between regions and large-scale networks that can be measured with resting-state fMRI. These group-based results are a necessary step toward development of biomarkers for clinical management of glioma patients, and provide additional evidence that global disruption of the DMN relates to cognitive impairment in glioma patients.

Subject-Specific Automatic Reconstruction of White Matter Tracts.

MRI-based tractography is still underexploited and unsuited for routine use in brain tumor surgery due to heterogeneity of methods and functional-anatomical definitions and above all, the lack of a turn-key system. Standardization of methods is therefore desirable, whereby an objective and reliable approach is a prerequisite before the results of any automated procedure can subsequently be validated and used in neurosurgical practice. In this work, we evaluated these preliminary but necessary steps in healthy volunteers. Specifically, we evaluated the robustness and reliability (i.e., test-retest reproducibility) of tractography results of six clinically relevant white matter tracts by using healthy volunteer data (N = 136) from the Human Connectome Project consortium. A deep learning convolutional network-based approach was used for individualized segmentation of regions of interest, combined with an evidence-based tractography protocol and appropriate post-tractography filtering. Robustness was evaluated by estimating the consistency of tractography probability maps, i.e., averaged tractograms in normalized space, through the use of a hold-out cross-validation approach. No major outliers were found, indicating a high robustness of the tractography results. Reliability was evaluated at the individual level. First by examining the overlap of tractograms that resulted from repeatedly processed identical MRI scans (N = 10, 10 iterations) to establish an upper limit of reliability of the pipeline. Second, by examining the overlap for subjects that were scanned twice at different time points (N = 40). Both analyses indicated high reliability, with the second analysis showing a reliability near the upper limit. The robust and reliable subject-specific generation of white matter tracts in healthy subjects holds promise for future validation of our pipeline in a clinical population and subsequent implementation in brain tumor surgery.

Executive functioning following surgery near the frontal aslant tract in low-grade glioma patients: A patient-specific tractography study.

BACKGROUND: The Frontal Aslant Tract (FAT) has been associated with executive functions (EF), but it remains unclear what role the FAT plays in EF, and whether preoperative dysfunction of the FAT is associated to long-lasting postsurgical executive impairments. METHODS: In this study, we examined the course of EF from pre-surgery (n = 75) to 3 (n = 61) and 12 (n = 25) months after surgery in patients with frontal and parietal low-grade gliomas (LGGs), to establish the degree to which long-term EF deficits exist. Secondly, we used patient-specific tractography to investigate the extent to which overlap of the tumor with the FAT, as well as integrity of the FAT, presurgery were related to EF on the short and longer term after surgery. RESULTS: LGG patients performed worse than healthy controls on all EF tests before and 3 months postsurgery. Whereas performances on three out of the four tests had normalized 1 year postsurgery (n = 26), performance on the cognitive flexibility test remained significantly worse than in healthy controls. Patients in whom the tumor overlapped with the core of the right FAT performed worse presurgery on three of the EF tests compared to those in whom the tumor did not overlap with the right FAT. Presurgical right FAT integrity was not related to presurgical EF, but only to postsurgical EF (from pre-to 3 months postsurgery). Longitudinal analyses demonstrated that patients with right (but not left) FAT core overlap performed on average worse over the pre- and postsurgical timepoints on the cognitive flexibility test. CONCLUSIONS: We emphasized that LGG patients perform worse than healthy controls on the EF tests, which normalizes 1-year postsurgery except for cognitive flexibility. Importantly, in patients with right hemispheric tumors, tumor involvement of the FAT was associated with worse pre- and 3- months postsurgical performance, specifically concerning cognitive flexibility.

Characterization and Classification of Spatial White Matter Tract Alteration Patterns in Glioma Patients Using Magnetic Resonance Tractography: A Systematic Review and Meta-Analysis.

INTRODUCTION: Magnetic resonance (MR) tractography can be used to study the spatial relations between gliomas and white matter (WM) tracts. Various spatial patterns of WM tract alterations have been described in the literature. We reviewed classification systems of these patterns, and investigated whether low-grade gliomas (LGGs) and high-grade gliomas (HGGs) demonstrate distinct spatial WM tract alteration patterns. METHODS: We conducted a systematic review and meta-analysis to summarize the evidence regarding MR tractography studies that investigated spatial WM tract alteration patterns in glioma patients. RESULTS: Eleven studies were included. Overall, four spatial WM tract alteration patterns were reported in the current literature: displacement, infiltration, disruption/destruction and edematous. There was a considerable heterogeneity in the operational definitions of these terms. In a subset of studies, sufficient homogeneity in the classification systems was found to analyze pooled results for the displacement and infiltration patterns. Our meta-analyses suggested that LGGs displaced WM tracts significantly more often than HGGs (n = 259 patients, RR: 1.79, 95% CI [1.14, 2.79], I2 = 51%). No significant differences between LGGs and HGGs were found for WM tract infiltration (n = 196 patients, RR: 1.19, 95% CI [0.95, 1.50], I2 = 4%). CONCLUSIONS: The low number of included studies and their considerable methodological heterogeneity emphasize the need for a more uniform classification system to study spatial WM tract alteration patterns using MR tractography. This review provides a first step towards such a classification system, by showing that the current literature is inconclusive and that the ability of fractional anisotropy (FA) to define spatial WM tract alteration patterns should be critically evaluated. We found variations in spatial WM tract alteration patterns between LGGs and HGGs, when specifically examining displacement and infiltration in a subset of the included studies.

Presurgical Executive Functioning in Low-Grade Glioma Patients Cannot Be Topographically Mapped.

Executive dysfunctions have a high prevalence in low-grade glioma patients and may be the result of structural disconnections of particular subcortical tracts and/or networks. However, little research has focused on preoperative low-grade glioma patients. The frontotemporoparietal network has been closely linked to executive functions and is substantiated by the superior longitudinal fasciculus. The aim of this study was to investigate their role in executive functions in low-grade glioma patients. Patients from two neurological centers were included with IDH-mutated low-grade gliomas. The sets of preoperative predictors were (i) distance between the tumor and superior longitudinal fasciculus, (ii) structural integrity of the superior longitudinal fasciculus, (iii) overlap between tumor and cortical networks, and (iv) white matter disconnection of the same networks. Linear regression and random forest analyses were performed. The group of 156 patients demonstrated significantly lower performance than normative samples and had a higher prevalence of executive impairments. However, both regression and random forest analyses did not demonstrate significant results, meaning that neither structural, cortical network overlap, nor network disconnection predictors explained executive performance. Overall, our null results indicate that there is no straightforward topographical explanation of executive performance in low-grade glioma patients. We extensively discuss possible explanations, including plasticity-induced network-level equipotentiality. Finally, we stress the need for the development of novel methods to unveil the complex and interacting mechanisms that cause executive deficits in low-grade glioma patients.

The Aftercare Survey: Assessment and intervention practices after brain tumor surgery in Europe.

Background: People with gliomas need specialized neurosurgical, neuro-oncological, psycho-oncological, and neuropsychological care. The role of language and cognitive recovery and rehabilitation in patients' well-being and resumption of work is crucial, but there are no clear guidelines for the ideal timing and character of assessments and interventions. The goal of the present work was to describe representative (neuro)psychological practices implemented after brain surgery in Europe. Methods: An online survey was addressed to professionals working with individuals after brain surgery. We inquired about the assessments and interventions and the involvement of caregivers. Additionally, we asked about recommendations for an ideal assessment and intervention plan. Results: Thirty-eight European centers completed the survey. Thirty of them offered at least one postsurgical (neuro)psychological assessment, mainly for language and cognition, especially during the early recovery stage and at long term. Twenty-eight of the participating centers offered postsurgical therapies. Patients who stand the highest chances of being included in evaluation and therapy postsurgically are those who underwent awake brain surgery, harbored a low-grade glioma, or showed poor recovery. Nearly half of the respondents offer support programs to caregivers, and all teams recommend them. Treatments differed between those offered to individuals with low-grade glioma vs those with high-grade glioma. The figure of caregiver is not yet fully recognized in the recovery phase. Conclusion: We stress the need for more complete rehabilitation plans, including the emotional and health-related aspects of recovery. In respondents' opinions, assessment and rehabilitation plans should also be individually tailored and goal-directed (eg, professional reinsertion).

Fatigue after neurosurgery in patients with a brain tumor: The role of autonomic dysregulation and disturbed sleep.

Background Fatigue is prevalent in patients with a brain tumor and high levels of fatigue persist after neurosurgical tumor resection. The underlying mechanisms are insufficiently understood and this study examines the role of autonomic nervous system dysregulation and objective sleep characteristics in fatigue among post-surgical patients. Methods Patients undergoing craniotomy (N = 52; age 52.1 ± 15.0 years; 44% women) were evaluated at 3 months after surgery (median = 86 days). Fatigue was measured using the Multidimensional Fatigue Inventory. Autonomic nervous system indices were based on 24-h heart rate variability (HRV) analysis. Sleep parameters were measured using actigraphy: total sleep duration, efficiency, onset latency and wake after sleep onset (WASO). Data analyses of this cross-sectional study included correlation and multiple regression analysis. Results Fatigue scores were significantly elevated in tumor resection patients compared to healthy reference norms (p's < 0.05) with no differences between patients with glioma (N = 32) versus meningioma (N = 20). Associations between HRV indices and fatigue were non-significant (r values <0.16, p values > 0.25). Sleep duration was associated with physical fatigue (r = 0.35, p = 0.02), whereas WASO was associated with mental fatigue levels (r = 0.40, p = 0.006). Disturbed sleep measures were associated with HRV indices of reduced parasympathetic nervous system activity in glioma patients but not in meningioma patients. Conclusions Multiple nocturnal awakenings may result in mental fatigue and longer sleep time was associated with physical fatigue, which may reflect compensatory sleep patterns. Future intervention studies addressing sleep quality may be beneficial in treating fatigue in patients following neurosurgery for tumor resection.

Broca-Wernicke theories: A historical perspective.

This chapter reviews the history of some of the theoretical models of aphasia, with a focus on the classic Broca-Wernicke model. It sets off in the 19th century when postmortem studies of patients with aphasia led to the first anatomic models of cerebral language representation. I chose to focus on the famous Broca-Wernicke model, not only because it remains influential in daily clinical decision making, but also because of the intriguing fact that the legacy of these physicians differs from their original opinions and theories. The chapter ends in the second half of the 20th century, before the advent of CT and MRI. Over time, there has never been much consensus on the anatomic location of specific language functions, and there remains an ongoing discussion between those who assign language functions to certain anatomic brain regions, and those who advocate that language functions cannot be localized as they are widely distributed across the brain. In retrospect, many historic figures such as Broca, Wernicke, Goldstein, or Luria, actually proposed theories that combined both localist and holist views, already reflecting our modern scientific views on language representation.

A systematic review of the use of subcortical intraoperative electrical stimulation mapping for monitoring of executive deficits and neglect: what is the evidence so far?

BACKGROUND: Over the past decade, the functional importance of white matter pathways has been increasingly acknowledged in neurosurgical planning. A method to directly study anatomo-functional correlations is direct electrical stimulation (DES). DES has been widely accepted by neurosurgeons as a reliable tool to minimize the occurrence of permanent postoperative motor, vision, and language deficits. In recent years, DES has also been used for stimulation mapping of other cognitive functions, such as executive functions and visuospatial awareness. METHODS: The aim of this review is to summarize the evidence so far from DES studies on subcortical pathways that are involved in visuospatial awareness and in the following three executive functions: (1) inhibitory control, (2) working memory, and (3) cognitive flexibility. RESULTS: Eleven articles reported on intraoperative electrical stimulation of white matter pathways to map the cognitive functions and explicitly clarified which subcortical tract was stimulated. The results indicate that the right SLF-II is involved in visuospatial awareness, the left SLF-III and possibly the right SLF-I are involved in working memory, and the cingulum is involved in cognitive flexibility. CONCLUSIONS: We were unable to draw any more specific conclusions, nor unequivocally establish the critical involvement of pathways in executive functions or visuospatial awareness due to the heterogeneity of the study types and methods, and the limited number of studies that assessed these relationships. Possible approaches for future research to obtain converging and more definite evidence for the involvement of pathways in specific cognitive functions are discussed.

The frontal aslant tract and its role in executive functions: a quantitative tractography study in glioma patients.

Focal white matter lesions can cause cognitive impairments due to disconnections within or between networks. There is some preliminary evidence that there are specific hubs and fiber pathways that should be spared during surgery to retain cognitive performance. A tract potentially involved in important higher-level cognitive processes is the frontal aslant tract. It roughly connects the posterior parts of the inferior frontal gyrus and the superior frontal gyrus. Functionally, the left frontal aslant tract has been associated with speech and the right tract with executive functions. However, there currently is insufficient knowledge about the right frontal aslant tract's exact functional importance. The aim of this study was to investigate the role of the right frontal aslant tract in executive functions via a lesion-symptom approach. We retrospectively examined 72 patients with frontal glial tumors and correlated measures from tractography (distance between tract and tumor, and structural integrity of the tract) with cognitive test performances. The results indicated involvement of the right frontal aslant tract in shifting attention and letter fluency. This involvement was not found for the left tract. Although this study was exploratory, these converging findings contribute to a better understanding of the functional frontal subcortical anatomy. Shifting attention and letter fluency are important for healthy cognitive functioning, and when impaired they may greatly influence a patient's wellbeing. Further research is needed to assess whether or not damage to the right frontal aslant tract causes permanent cognitive impairments, and consequently identifies this tract as a critical pathway that should be taken into account during neurosurgical procedures.

eHealth cognitive rehabilitation for brain tumor patients: results of a randomized controlled trial.

BACKGROUND: Evidence-based cognitive rehabilitation programs for brain tumor patients are not widely available, despite the high need. We aimed to evaluate the effects of a tablet-based cognitive rehabilitation program on cognitive performance, cognitive complaints, fatigue, and psychological distress in primary brain tumor patients following neurosurgery. Also, attrition, adherence and patient satisfaction with the program were evaluated. METHODS: Adults with presumed low-grade glioma and meningioma were recruited before surgery. Three months thereafter, participants were allocated to the intervention group or waiting-list control group using minimization. The 10-week eHealth app ReMind, based on the effective face-to-face intervention, consisted of psychoeducation, strategy-training and attention retraining. Performance-based cognitive outcomes and patient-reported outcomes were assessed before surgery and 3, 6 and 12 months thereafter. Mean scores, percentages of cognitively impaired individuals and reliable change indices (RCIs) were compared between groups. RESULTS: Sixty-two out of 183 eligible patients were randomized. Of the people who declined, 56% reported that participation would to be too burdensome. All participants found a tablet-app suitable for delivery of cognitive rehabilitation and 90% rated the program as "good" or "excellent". Performance-based cognitive outcomes and patient-reported outcomes did not significantly differ in group means over time nor RCIs between the intervention (final n = 20) and control group (final n = 25). CONCLUSIONS: Recruitment at this early stage was difficult, resulting in limited statistical power. No significant effects were demonstrated, while adherence and satisfaction with the eHealth program were good. In clinical practice, ReMind may be helpful, if timing would be adapted to patients' needs.

A functional MRI study of presurgical cognitive deficits in glioma patients.

BACKGROUND: The main goal of this functional MRI (fMRI) study was to examine whether cognitive deficits in glioma patients prior to treatment are associated with abnormal brain activity in either the central executive network (CEN) or default mode network (DMN). METHODS: Forty-six glioma patients, and 23 group-matched healthy controls (HCs) participated in this fMRI experiment, performing an N-back task. Additionally, cognitive profiles of patients were evaluated outside the scanner. A region of interest-based analysis was used to compare brain activity in CEN and DMN between groups. Post hoc analyses were performed to evaluate differences between low-grade glioma (LGG) and high-grade glioma (HGG) patients. RESULTS: In-scanner performance was lower in glioma patients compared to HCs. Neuropsychological testing indicated cognitive impairment in LGG as well as HGG patients. fMRI results revealed normal CEN activation in glioma patients, whereas patients showed reduced DMN deactivation compared to HCs. Brain activity levels did not differ between LGG and HGG patients. CONCLUSIONS: Our study suggests that cognitive deficits in glioma patients prior to treatment are associated with reduced responsiveness of the DMN, but not with abnormal CEN activation. These results suggest that cognitive deficits in glioma patients reflect a reduced capacity to achieve a brain state necessary for normal cognitive performance, rather than abnormal functioning of executive brain regions. Solely focusing on increases in brain activity may well be insufficient if we want to understand the underlying brain mechanism of cognitive impairments in patients, as our results indicate the importance of assessing deactivation.

fMRI Resting-State Connectivity between Language and Nonlanguage Areas as Defined by Intraoperative Electrocortical Stimulation in Low-Grade Glioma Patients.

BACKGROUND AND OBJECTIVES: It remains to be determined whether noninvasive functional imaging techniques can rival the clinical potential of direct electrocortical stimulation (DES). In this study, we compared the results of resting-state functional magnetic resonance imaging (rs-fMRI) to those of DES for language mapping. Our goals were twofold: (1) to replicate a previous study that demonstrated that resting-state connectivity (RSC) was significantly larger between positive DES language sites than between negative DES language sites and (2) to compare the spatial resolution of rs-fMRI to that of DES. METHODS: We conducted a retrospective study of nine low-grade glioma patients. Language sites were identified by intraoperative DES. We compared RSC values between and within groups of DES-positive and DES-negative regions of interest (ROIs). Both close-negative sites (i.e., DES-negative sites <1 cm apart from and on the same gyrus as DES-positive sites) and far-negative sites (i.e., purely randomly chosen sites not in the vicinity of the tumor or of the DES-positive sites but on the same lobe) were included. Receiver operating characteristics were used to quantify comparisons. RESULTS: Functional connectivity between all positive language sites was on average significantly higher than between all close-negative sites and between all far-negative sites. The functional connectivity between the positive language ROIs and their respective close-negative control sites was not smaller than between all positive language sites. CONCLUSION: rs-fMRI likely reflects similar neural information as detected with DES, but in its current form does not reach the spatial resolution of DES.

Executive functional deficits during electrical stimulation of the right frontal aslant tract.

Direct electrical stimulation mapping was used to map executive functions during awake surgery of a patient with a right frontal low-grade glioma. We specifically targeted the frontal aslant tract, as this pathway had been infiltrated by the tumor. The right frontal aslant tract has been implicated in executive functions in the neuroscientific literature, but is yet of unknown relevance for clinical practice. Guided by tractography, electrical stimulation of the frontal aslant tract disrupted working memory and inhibitory functions. In this report we illustrate the dilemmas that neurosurgeons face when balancing maximal tumor resection against optimal cognitive performance. In particular, we emphasize that intraoperative tasks that target cognitive functions should be carefully introduced in clinical practice to prevent clinically irrelevant responses and too early termination of the resection.

The APOE ε4 allele in relation to pre- and postsurgical cognitive functioning of patients with primary brain tumors.

BACKGROUND: Recent studies suggest a relationship between the APOE ε4 allele and cognitive outcome in patients treated for malignant brain tumors. Still, longitudinal investigations that include a pretreatment cognitive assessment are lacking and APOE's effects in patients with benign tumors are understudied. This study investigated presurgical cognitive performance and postsurgical change in ε4-carrying and non-carrying patients with glioma and meningioma. METHODS: Neuropsychological test scores (CNS Vital Signs battery [seven measures], Digit Span Forward/Backward, Letter Fluency test) were obtained as part of a prospective study in which patients with meningioma and glioma underwent cognitive assessment 1 day before (T0, n = 505) and 3 (T3, n = 418) and 12 months after (T12, n = 167) surgery. APOE isoforms were identified retrospectively. ε4 carriers and non-carriers were compared with regard to pretreatment cognitive performance on the group and individual level. Changes in performances over time were compared with longitudinal mixed model analysis in the total sample and the subgroup receiving adjuvant treatment. RESULTS: Carriers and non-carriers did not differ with regard to pretreatment performance. No significant main effect of ε4 carrier status or interaction between time (T0-T12) and carrier status was found on any of the tests in the whole sample nor in the sample receiving adjuvant treatment. CONCLUSIONS: This study found no evidence of increased vulnerability for pretreatment cognitive dysfunction or cognitive decline within 1 year after surgery in APOE ε4-carrying meningioma and glioma patients. Investigations that include larger samples at longer-term follow-up are recommended to investigate potential late treatment effects.

Correction to: Automatic identification of atypical clinical fMRI results.

The above article was published online with an incorrect affiliation.