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.

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.

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 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.

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.

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.

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.

Presurgical Identification of Patients With Glioblastoma at Risk for Cognitive Impairment at 3-Month Follow-up.

BACKGROUND: Pre- and postoperative cognitive deficits have repeatedly been demonstrated in patients with glioblastoma (GBM). OBJECTIVE: To identify presurgical risk factors that facilitate the identification of GBM patients at risk for postoperative cognitive impairment. METHODS: Patients underwent neuropsychological assessment using Central Nervous System Vital Signs 1 d before (T0) and 3 mo after surgery (T3). Patients' standardized scores on 7 cognitive domains were compared to a normative sample using one-sample z tests. Reliable change indices with correction for practice effects were calculated to assess cognitive changes in individual patients over time. Logistic regression models were performed to assess presurgical sociodemographic, clinical, psychological, and cognitive risk factors for postoperative cognitive impairments. RESULTS: At T0, 208 patients were assessed, and 136 patients were retested at T3. Patients showed significantly lower performance both prior to and 3 mo after surgery on all cognitive domains compared to healthy controls. Improvements and declines over time occurred respectively in 11% to 32% and 6% to 26% of the GBM patients over the domains. The regression models showed that low preoperative cognitive performance posits a significant risk factor for postoperative cognitive impairment on all domains, and female sex was a risk factor for postoperative impairments in Visual Memory. CONCLUSION: We demonstrated preoperative cognitive risk factors that enable the identification of GBM patients who are at risk for cognitive impairment 3 mo after surgery. This information can help to inform patients and clinicians at an early stage, and emphasizes the importance of recognizing, assessing, and actively dealing with cognitive functioning in the clinical management of GBM patients.

Prevalence and correlates of fatigue in patients with meningioma before and after surgery.

BACKGROUND: Fatigue is a common symptom in patients with brain tumors, but comprehensive studies on fatigue in patients with meningioma specifically are lacking. This study examined the prevalence and correlates of fatigue in meningioma patients. METHODS: Patients with grade I meningioma completed the Multidimensional Fatigue Inventory (MFI-20) before and 1 year after neurosurgery. The MFI consists of 5 subscales: General Fatigue, Physical Fatigue, Mental Fatigue, Reduced Motivation, and Reduced Activity. Patients' scores were compared with normative data. Preoperative fatigue was compared with postoperative fatigue. Correlations with sex, age, education, tumor hemisphere, preoperative tumor volume, antiepileptic drugs (AEDs), symptoms of anxiety/depression, and self-reported cognitive complaints were explored. RESULTS: Questionnaires were completed by 65 patients preoperatively, and 53 patients postoperatively. Of 34 patients, data from both time points were available. Patients had significantly higher fatigue levels on all subscales compared to normative values at both time points. Mean scores on General Fatigue, Physical Fatigue, and Mental Fatigue remained stable over time and improvements were observed on Reduced Motivation and Reduced Activity. Preoperatively, the prevalence of high fatigue (Z-score ≥ 1.3) varied between 34% for Reduced Motivation and 43% for General Fatigue/Mental Fatigue. The postoperative prevalence ranged from 19% for Reduced Activity to 49% on Mental Fatigue. Fatigue was associated with cognitive complaints, anxiety and depression, but not with education, tumor lateralization, tumor volume, or AEDs. CONCLUSION: Fatigue is a common and persistent symptom in patients with meningioma undergoing neurosurgery. Findings emphasize the need for more research and appropriate care targeting fatigue for meningioma patients.

Task-evoked reconfiguration of the fronto-parietal network is associated with cognitive performance in brain tumor patients.

In healthy participants, the strength of task-evoked network reconfigurations is associated with cognitive performance across several cognitive domains. It is, however, unclear whether the capacity for network reconfiguration also plays a role in cognitive deficits in brain tumor patients. In the current study, we examined whether the level of reconfiguration of the fronto-parietal ('FPN') and default mode network ('DMN') during task execution is correlated with cognitive performance in patients with different types of brain tumors. For this purpose, we combined data from a resting state and task-fMRI paradigm in patients with a glioma or meningioma. Cognitive performance was measured using the in-scanner working memory task, as well as an out-of-scanner cognitive flexibility task. Task-evoked changes in functional connectivity strength (defined as the mean of the absolute values of all connections) and in functional connectivity patterns within and between the FPN and DMN did not differ significantly across meningioma and fast (HGG) and slowly growing glioma (LGG) patients. Across these brain tumor patients, a significant and positive correlation was found between the level of task-evoked reconfiguration of the FPN and cognitive performance. This suggests that the capacity for FPN reconfiguration also plays a role in cognitive deficits in brain tumor patients, as was previously found for normal cognitive performance in healthy controls.

The SAFE-trial: Safe surgery for glioblastoma multiforme: Awake craniotomy versus surgery under general anesthesia. Study protocol for a multicenter prospective randomized controlled trial.

BACKGROUND: Surgery of GBM nowadays is usually performed under general anesthesia (GA) and resections are often not as aggressive as possible, due to the chance of seriously damaging the patient with a rather low life expectancy. A surgical technique optimizing resection of the tumor in eloquent areas but preventing neurological deficits is necessary to improve survival and quality of life in these patients. Awake craniotomy (AC) with the use of cortical and subcortical stimulation has been widely implemented for low-grade glioma resections (LGG), but not yet for GBM. AC has shown to increase resection percentage and preserve quality of life in LGG and could thus be of important value in GBM surgery. METHODS/DESIGN: This study is a prospective, multicenter, randomized controlled trial (RCT). Consecutive patients with a glioblastoma in or near eloquent areas (Sawaya grading II/III) will be 1:1 randomized to awake craniotomy or craniotomy under general anesthesia. 246 patients will be included in neurosurgical centers in the Netherlands and Belgium. Primary end-points are: 1) Postoperative neurological morbidity and 2) Proportion of patients with gross-total resections. Secondary end-points are: 1) Health-related quality of life; 2) Progression-free survival (PFS); 3) Overall survival (OS) and 4) Frequency and severity of Serious Adverse Effects in each group. Also, a cost-benefit analysis will be performed. All patients will receive standard adjuvant treatment with concomitant chemoradiotherapy. DISCUSSION: This RCT should demonstrate whether AC is superior to craniotomy under GA on neurological morbidity, extent of resection and survival for glioblastoma resections in or near eloquent areas. TRIAL REGISTRATION: Clinicaltrials.gov: NCT03861299 Netherlands Trial Register (NTR): NL7589.

Cognitive functioning in patients with low-grade glioma: effects of hemispheric tumor location and surgical procedure.

OBJECTIVE: The authors evaluated the cognitive performance of patients with low-grade glioma (LGG) before and after surgery, and specifically investigated 1) the effects of hemispheric tumor location and 2) the type of surgery (either with or without intraoperative stimulation mapping [ISM]). METHODS: Patients underwent neuropsychological assessment 1 day before (T0) and 3 months after (T3) surgery. ISM targeted motor and/or language functions, but no other cognitive functions. Using 2-way mixed ANOVAs, differences between groups (i.e., for patients with right- vs left-sided lesions and normative controls [NCs], and also for patients operated on with vs without ISM and NCs), effects over time (T0-T3), and interaction effects in cognitive functioning were explored. Individual changes over time were assessed with reliable change indices for each neuropsychological test. RESULTS: In total, 77 patients with LGG were included (38 and 39 patients with right- and left-sided lesions, respectively; and 42 patients with and 35 patients without ISM). The majority of patients who were operated on with ISM had left-sided lesions. Patients with right- and left-sided lesions scored significantly lower on 6 and 3 out of 8 tests, respectively, compared to NCs. No significant differences between hemispheric groups were found at T0 or at T3. Patients with left-sided lesions showed significant deterioration of performance on verbal memory and sustained attention over time. Patients who underwent operation with versus without ISM scored significantly lower on 6 and 3 out of 8 tests, respectively, compared to NCs. Patients in the ISM group scored significantly lower on the Stroop test, shifting attention test, and verbal fluency test than patients without ISM. Also, the ISM group showed a significant decline in mean cognitive flexibility and sustained attention performance over time. CONCLUSIONS: Cognitive impairments were found in patients irrespective of hemispheric tumor location, whereby patients who were operated on with ISM performed slightly worse after surgery than patients without ISM. The authors conclude that there is room for improvement of cognitive functioning in surgically treated patients with LGG. The use of specific tests for higher cognitive functions during surgery may potentially improve functional outcome, but that is to be determined in future studies and balanced against oncological outcome. Implementation of neuropsychological assessments into the clinical management of patients with LGG should be encouraged, to inform and alert patients and clinicians on the status of cognitive functioning.

The effect of response frequency on cognitive brain activity during an alertness task.

A required response forces the brain to react overtly on a stimulus. This may be a factor that influences cognitive activity during a task, as it could facilitate for instance alertness, especially in tasks that are relatively easy. In the current article, we therefore tested the hypothesis that response frequency affects cognitive brain activity in an alertness task. In this 3T functional MRI study, healthy volunteers performed a continuous performance task with three conditions with increasing response frequency. Only scans during presentation of non-targets were analyzed, to exclude activity related to the change in frequency in response selection and motor responses between conditions. To evaluate changes in cognitive brain activity, a network analysis was performed based on two main networks including regions with task-induced activation and task-induced deactivation. We tested for differences in brain activity as an effect of target frequency. Performance results indicated no effect of target frequency on accuracy or reaction time. During non-targets, we found significant signal changes in TID for all three conditions, whereas TIA showed no significant signal changes in any condition. Target frequency did not have a significant effect on the level of signal change at network level, as well as at individual region level. Our study showed predominantly deactivation during non-responses in all three task conditions. Furthermore, our results indicate that response frequency does not influence brain activity during an alertness task. Our results provide additional information relevant for the understanding of the neurophysiological implementation of cognitive control or alertness.

Brain Activity Associated With Expected Task Difficulty.

Previous research shows that people can use a cue to mentally prepare for a cognitive challenge. The response to a cue has been defined as phasic alertness which is reflected in faster responses and increased activity in frontal, parietal, thalamic, and visual brain regions. We examine if and how phasic alertness can be tuned to the expected difficulty of an upcoming challenge. If people in general are able to tune their level of alertness, then an inability to tune may be linked to disease. Twenty-two healthy volunteers performed a cued visual perception task with two levels of task difficulty. Performance and brain activity were compared between these two levels. Performance was lower for difficult stimuli than for easy stimuli. For both cue types, participants showed activation in a network associated with central executive function and deactivation in regions of the default mode network (DMN) and visual cortex. Deactivation was significantly stronger for cues signaling difficult stimuli than for cues signaling easy stimuli. This effect was most prominent in medial prefrontal gyrus, visual, and temporal cortices. Activation did not differ between the cues. Our study shows that phasic alertness is represented by activated as well as deactivated brain regions. However only deactivated brain regions tuned their level of activity to the expected task difficulty. These results suggest that people, in general, are able to tune their level of alertness to an upcoming task. Cognition may be facilitated by a brain-state coupled to expectations about an upcoming cognitive challenge. Unique identifier = 842003004.

Cognitive functioning in glioma patients is related to functional connectivity measures of the non-tumoural hemisphere.

Previous studies have shown that cognitive functioning in patients with brain tumour is associated with the functional network characteristics of specific resting-state networks or with whole-brain network characteristics. These studies, however, did not acknowledge the functional contribution of areas in the contralesional, non-tumoural hemisphere, even though these healthy remote areas likely play a critical role in compensating for the loss of function in damaged tissue. In the current study, we examined whether there is an association between cognitive performance and functional network features of the contralesional hemisphere of patients with glioma. We found that local efficiency of the contralesional hemisphere was associated with performance on the reaction time domain, whereas contralesional assortativity was associated with complex attention and cognitive flexibility scores. Our results suggest that a less segregated organization of the contralesional hemisphere is associated with better reaction time scores, whereas a better spread of information over the contralesional hemisphere through mutually interconnected contralesional hubs is associated with better cognitive flexibility and better complex attention scores. These findings urge researchers to recognize the functional contribution of remote, undamaged regions and to focus more on the graph metrics of the contralesional hemisphere in the search for predictors of cognitive functioning in patients with brain tumour.