Perioperative Neurocognitive Function in Glioma Surgery.

PURPOSE OF REVIEW: This review provides a concise overview of the recent literature regarding preoperative and postoperative neurocognitive functioning (NCF) in patients with glioma. Brief discussion also covers contemporary intraoperative brain mapping work, with a focus on potential influence of mapping upon NCF outcomes following awake surgery. RECENT FINDINGS: Most patients with glioma exhibit preoperative NCF impairment, with severity varying by germ line and tumoral genetics, tumor grade, and lesion location, among other characteristics. Literature regarding postoperative NCF changes is mixed, though numerous studies indicate a majority of patients exhibit immediate and short-term worsening. This is often followed by recovery over several months; however, a substantial portion of patients harbor persisting declines. Decline appears related to surgically-induced structural and functional brain alterations, both local and distal to the tumor and resection cavity. Importantly, NCF decline may be mitigated to some extent by intraoperative brain mapping, including mapping of both language-mediated and nonverbal functions. Research regarding perioperative NCF in patients with glioma has flourished over recent years. While this has increased our understanding of contributors to NCF and risk of decline associated with surgical intervention, more work is needed to better preserve NCF throughout the disease course.

Intraoperative language mapping guided by real-time visualization of gamma band modulation electrocorticograms: Case report and proof of concept.

Background: Electrocorticography (ECoG) language mapping is often performed extraoperatively, frequently involves offline processing, and relationships with direct cortical stimulation (DCS) remain variable. We sought to determine the feasibility and preliminary utility of an intraoperative language mapping approach guided by real-time visualization of electrocorticograms. Methods: A patient with astrocytoma underwent awake craniotomy with intraoperative language mapping, utilizing a dual iPad stimulus presentation system coupled to a real-time neural signal processing platform capable of both ECoG recording and delivery of DCS. Gamma band modulations in response to 4 language tasks at each electrode were visualized in real-time. Next, DCS was conducted for each neighboring electrode pair during language tasks. Results: All language tasks resulted in strongest heat map activation at an electrode pair in the anterior to mid superior temporal gyrus. Consistent speech arrest during DCS was observed for Object and Action naming tasks at these same electrodes, indicating good correspondence with ECoG heat map recordings. This region corresponded well with posterior language representation via preoperative functional MRI. Conclusions: Intraoperative real-time visualization of language task-based ECoG gamma band modulation is feasible and may help identify targets for DCS. If validated, this may improve the efficiency and accuracy of intraoperative language mapping.

Decoding the clinical effects of low-grade glioma-induced cortical excitability.

OBJECTIVE: Patients with low-grade glioma (LGG) in eloquent regions often present with seizures, and findings on detailed neuropsychological testing are often abnormal. This study evaluated the association between cortical excitability, seizures, and cognitive function in patients with LGG. METHODS: LGG patients who underwent transcranial magnetic stimulation (TMS) from January 2021 to December 2022 were studied. Cortical excitability was measured using the resting motor thresholds (RMTs) of the upper and lower extremities. Early postoperative seizures served as the seizure endpoint. Neuropsychological assessment was completed prior to surgery contemporaneous with the TMS studies. RESULTS: A total of 31 patients were analyzed for seizure outcome. Median (interquartile range [IQR]) upper-extremity RMT was 39% (34%-46%) of maximum stimulator output, and the median (IQR) lower-extremity RMT was 69% (51%-79%). Lower-extremity RMT was higher in patients with early postoperative seizures, especially in those with motor region tumors (p = 0.02); however, RMT was not associated with seizures at presentation or long-term seizure control. A total of 26 patients completed neuropsychological assessment. There were significant negative correlations between upper-extremity RMT and psychomotor processing speed (Wechsler Adult Intelligence Scale-Fourth Edition [WAIS-IV] Processing Speed Index r = -0.42, p = 0.031; WAIS-IV Coding r = -0.41, p = 0.036; WAIS-IV Symbol Search r = -0.39, p = 0.048), executive function (Trail Making Test Part B r = -0.41, p = 0.036), and hand dexterity (Grooved Pegboard Test r = -0.50, p = 0.047). CONCLUSIONS: RMT was positively correlated with early postoperative seizure risk and negatively correlated with psychomotor processing speed, executive function, and hand dexterity. These findings support the theory of local and regional resting oscillatory network dysfunction from a glioma-brain network.

Cerebrovascular Reactivity Mapping Using Resting-State Functional MRI in Patients With Gliomas.

BACKGROUND: Recently, a data-driven regression analysis method was developed to utilize the resting-state (rs) blood oxygenation level-dependent signal for cerebrovascular reactivity (CVR) mapping (rs-CVR), which was previously optimized by comparing with the CO2 inhalation-based method in health subjects and patients with neurovascular diseases. PURPOSE: To investigate the agreement of rs-CVR and the CVR mapping with breath-hold MRI (bh-CVR) in patients with gliomas. STUDY TYPE: Retrospective. POPULATION: Twenty-five patients (12 males, 13 females; mean age ± SD, 48 ± 13 years) with gliomas. FIELD STRENGTH/SEQUENCE: Dynamic T2*-weighted gradient-echo echo-planar imaging during a breath-hold paradigm and during the rs on a 3-T scanner. ASSESSMENT: rs-CVR with various frequency ranges and resting-state fluctuation amplitude (RSFA) were assessed. The agreement between each rs-based CVR measurement and bh-CVR was determined by voxel-wise correlation and Dice coefficient in the whole brain, gray matter, and the lesion region of interest (ROI). STATISTICAL TESTS: Voxel-wise Pearson correlation, Dice coefficient, Fisher Z-transformation, repeated-measure analysis of variance and post hoc test with Bonferroni correction, and nonparametric repeated-measure Friedman test and post hoc test with Bonferroni correction were used. Significance was set at P < 0.05. RESULTS: Compared with bh-CVR, the highest correlations were found at the frequency bands of 0.04-0.08 Hz and 0.02-0.04 Hz for rs-CVR in both whole brain and the lesion ROI. RSFA had significantly lower correlations than did rs-CVR of 0.02-0.04 Hz and a wider frequency range (0-0.1164 Hz). Significantly higher correlations and Dice coefficient were found in normal tissues than in the lesion ROI for all three methods. DATA CONCLUSION: The optimal frequency ranges for rs-CVR are determined by comparing with bh-CVR in patients with gliomas. The rs-CVR method outperformed the RSFA. Significantly higher correlation and Dice coefficient between rs- and bh-CVR were found in normal tissue than in the lesion. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY STAGE: 2.

Effect of brain normalization methods on the construction of functional connectomes from resting-state functional MRI in patients with gliomas.

PURPOSE: Spatial normalization is an essential step in resting-state functional MRI connectomic analysis with atlas-based parcellation, but brain lesions can confound it. Cost-function masking (CFM) is a popular compensation approach, but may not benefit modern normalization methods. This study compared three normalization methods with and without CFM and determined their impact on connectomic measures in patients with glioma. METHODS: Fifty patients with glioma were included. T1 -weighted images were normalized using three different methods in SPM12, with and without CFM, which were then overlaid on the ICBM152 template and scored by two neuroradiologists. The Dice coefficient of gray-matter correspondence was also calculated. Normalized resting-state functional MRI data were parcellated using the AAL90 atlas to construct an individual connectivity matrix and calculate connectomic measures. The R2 among the different normalization methods was calculated for the connectivity matrices and connectomic measures. RESULTS: The older method (Original) performed significantly worse than the modern methods (Default and DARTEL; P < .005 in observer ranking). The use of CFM did not significantly improve the normalization results. The Original method had lower correlation with the Default and DARTEL methods (R2 = 0.71-0.74) than Default with DARTEL (R2 = 0.96) in the connectivity matrix. The clustering coefficient appears to be the most, and modularity the least, sensitive connectomic measures to normalization performance. CONCLUSION: The spatial normalization method can have an impact on resting-state functional MRI connectome and connectomic measures derived using atlas-based brain parcellation. In patients with glioma, this study demonstrated that Default and DARTEL performed better than the Original method, and that CFM made no significant difference.

Alterations in Functional Connectomics Associated With Neurocognitive Changes Following Glioma Resection.

BACKGROUND: Decline in neurocognitive functioning (NCF) often occurs following brain tumor resection. Functional connectomics have shown how neurologic insults disrupt cerebral networks underlying NCF, though studies involving patients with brain tumors are lacking. OBJECTIVE: To investigate the impact of brain tumor resection upon the connectome and relationships with NCF outcome in the early postoperative period. METHODS: A total of 15 right-handed adults with left perisylvian glioma underwent resting-state functional magnetic resonance imaging (rs-fMRI) and neuropsychological assessment before and after awake tumor resection. Graph theoretical analysis was applied to rs-fMRI connectivity matrices to calculate network properties. Network properties and NCF measures were compared across the pre- to postoperative periods with matched pairs Wilcoxon signed-rank tests. Associations between pre- to postoperative change in network and NCF measures were determined with Spearman rank-order correlations (ρ). RESULTS: A majority of the sample showed postoperative decline on 1 or more NCF measures. Significant postoperative NCF decline was found across measures of verbal memory, processing speed, executive functioning, receptive language, and a composite index. Regarding connectomic properties, betweenness centrality and assortativity were significantly smaller postoperatively, and reductions in these measures were associated with better NCF outcomes. Significant inverse associations (ρ = -.51 to -.78, all P < .05) were observed between change in language, executive functioning, and learning and memory, and alterations in segregation, centrality, and resilience network properties. CONCLUSION: Decline in NCF was common shortly following resection of glioma involving eloquent brain regions, most frequently in verbal learning/memory and executive functioning. Better postoperative outcomes accompanied reductions in centrality and resilience connectomic measures.

Impaired neurocognitive function in glioma patients: from pathophysiology to novel intervention strategies.

PURPOSE OF REVIEW: This review succinctly summarizes the recent literature regarding etiological contributors to impaired neurocognitive function (NCF) in adult patients with glioma. A brief overview of intervention and prevention strategies is also provided. RECENT FINDINGS: A majority of patients with glioma exhibit NCF deficits, most frequently in memory and executive functioning. Impairments are often disabling and associated with reduced quality of life and survival. Cause is multifactorial and includes the tumour itself, treatments received and associated comorbidities. Although modern techniques such as brain mapping, dosing modifications and prophylactic medication aim to improve the NCF outcomes following neurosurgical resection and radiation therapy, a sizeable proportion of patients continue to evidence treatment-related NCF declines related to adverse effects to both local and distributed cerebral networks. Numerous patient and tumour characteristics, including genetic markers and sociodemographic factors, influence the pattern and severity of NCF impairment. Some rehabilitative and pharmacologic approaches show promise in mitigating NCF impairment in this population, though benefits are somewhat modest and larger scale intervention studies are needed. SUMMARY: Research regarding NCF in patients with glioma has dramatically proliferated, providing insights into the mechanisms underlying impaired NCF and pointing to potential interventions, though further work is needed.

Language supplementary motor area syndrome correlated with dynamic changes in perioperative task-based functional MRI activations: case report.

Supplementary motor area (SMA) syndrome is well known; however, the mechanism underlying recovery from language SMA syndrome is unclear. Herein the authors report the case of a right-handed woman with speech aphasia following resection of an oligodendroglioma located in the anterior aspect of the left superior frontal gyrus. The patient exhibited language SMA syndrome, and functional MRI (fMRI) findings 12 days postoperatively demonstrated a complete shift of blood oxygen level-dependent (BOLD) activation to the contralateral right language SMA/pre-SMA as well as coequal activation and an increased volume of activation in the left Broca's area and the right Broca's homolog. The authors provide, to the best of their knowledge, the first description of dynamic changes in task-based hemispheric language BOLD fMRI activations across the preoperative, immediate postoperative, and more distant postoperative settings associated with the development and subsequent complete resolution of the clinical language SMA syndrome.

Presurgical resting-state functional MRI language mapping with seed selection guided by regional homogeneity.

PURPOSE: Resting-state functional MRI (rs-FMRI) has shown potential for presurgical mapping of eloquent cortex when a patient's performance on task-based FMRI is compromised. The seed-based analysis is a practical approach for detecting rs-FMRI functional networks; however, seed localization remains challenging for presurgical language mapping. Therefore, we proposed a data-driven approach to guide seed localization for presurgical rs-FMRI language mapping. METHODS: Twenty-six patients with brain tumors located in left perisylvian regions had undergone task-based FMRI and rs-FMRI before tumor resection. For the seed-based rs-FMRI language mapping, a seeding approach that integrates regional homogeneity and meta-analysis maps (RH+MA) was proposed to guide the seed localization. Canonical and task-based seeding approaches were used for comparison. The performance of the 3 seeding approaches was evaluated by calculating the Dice coefficients between each rs-FMRI language mapping result and the result from task-based FMRI. RESULTS: With the RH+MA approach, selecting among the top 6 seed candidates resulted in the highest Dice coefficient for 81% of patients (21 of 26) and the top 9 seed candidates for 92% of patients (24 of 26). The RH+MA approach yielded rs-FMRI language mapping results that were in greater agreement with the results of task-based FMRI, with significantly higher Dice coefficients (P < .05) than that of canonical and task-based approaches within putative language regions. CONCLUSION: The proposed RH+MA approach outperformed the canonical and task-based seed localization for rs-FMRI language mapping. The results suggest that RH+MA is a robust and feasible method for seed-based functional connectivity mapping in clinical practice.

Driver safety in patients with primary brain tumors.

BACKGROUND: Operating a motor vehicle involves multiple cognitive and sensorimotor faculties. Neurological conditions pose driving risk, but this has not been examined in patients with primary brain tumors. METHODS: Sixty-four patients with primary brain tumors (32 left hemisphere; 69% glioblastoma) completed the Cognitive Behavioral Driver's Inventory (CBDI). A subset also completed broader cognitive testing. Patient characteristics, CBDI measures, and broader neuropsychological test scores were compared between Passing and Nonpassing groups. Follow-up logistic regression analyses identified patient characteristics and CBDI measures predictive of Pass/Nonpass outcome. Point-biserial correlations determined associations between neuropsychological tests and CBDI outcome. RESULTS: Sixty-nine percent of patients were classified as passing the CBDI. Nonpassing patients were older and more likely to have WHO grade IV and temporal lobe tumors. Age was the most salient predictor of CBDI performance. CBDI measures of speeded visual search and set-shifting, speeded response inhibition, vigilance and freedom from distractibility, and basic visual scanning speed were predictive of Pass/Nonpass outcome. Neuropsychological tests of memory in particular, but also speeded visual scanning and discrimination, executive function, basic visual attention, visuoconstruction, and manual dexterity (dominant hand), were associated with CBDI outcome. CONCLUSIONS: A sizeable proportion of patients with primary brain tumors appear at risk of driving difficulty, particularly those with higher-grade tumors and of older age. Memory, visual attention, and executive difficulties appear to contribute most to driving safety risk as determined by the CBDI. These results highlight the importance of driving safety screening in this population.

Monitoring of Neurocognitive Function in the Care of Patients with Brain Tumors.

PURPOSE OF REVIEW: A detailed characterization of the nature of neurocognitive impairment in patients with brain tumors is provided, as well as considerations for clinical practice regarding neuropsychological assessment throughout the disease course. RECENT FINDINGS: Neurocognitive impairment is common in patients with brain tumors and may result from the tumor itself, as a consequence of treatment, including surgery, chemotherapy, and radiation, or in association with supportive care medications (e.g., anticonvulsant and pain medications). Serial surveillance of neurocognitive functioning in this population can facilitate medical decision-making and inform recommendations to improve patient daily functioning and quality of life. Neuropsychological assessment is increasingly recognized as a critical component of the multidisciplinary care of patients with brain tumors and has already had practice-changing effects. Further understanding of genetic risk factors for neurocognitive decline along with the development of novel assessment and intervention strategies may further enhance functioning and general well-being in this patient population.

Depressive symptoms and executive function in relation to survival in patients with glioblastoma.

INTRODUCTION: Depression and neurocognitive function, particularly executive functioning (EF), have been associated with overall survival (OS) in patients with glioblastoma (GBM). However, the combined effect of depressive symptoms and impaired EF upon OS has not been reported. METHODS: Patients with GBM (N = 102) completed neuropsychological assessment postoperatively, including the Beck Depression Inventory-Second Edition (BDI-II) and the Trail Making Test Part B (TMTB). Median splits were used to determine cut-points denoting elevated depressive symptoms on the BDI-II and impaired EF on TMTB. Patients were stratified into four groups: low depressive symptoms/low EF impairment (- Dep/- Imp; N = 23), high depressive symptoms/low EF impairment (+ Dep/- Imp; N = 28), low depressive symptoms/high EF impairment (- Dep/+Imp; N = 28), and high depressive symptoms/high EF impairment (+ Dep/+Imp; N = 23). The Kaplan-Meier method, log-rank test, and Cox regression were used to examine differences in survival between groups. RESULTS: Relative to - Dep/- Imp patients (median OS = 22.8 months), median OS in all other patient groups was shorter (+ Dep/- Imp OS = 16.6; - Dep/+Imp OS = 14.8; +Dep/+Imp OS = 10.8; all p < .05). With the exception of KPS and age, groups did not differ in distribution of clinical and demographic characteristics. Neither KPS nor age modified the independent effect of BDI-II and TMTB on OS in Cox regression models. CONCLUSIONS: The presence of depressive symptoms and impaired EF are independently associated with shorter OS in patients with GBM. These results suggest that routine neuropsychological assessment of mood and cognition may help refine prognosis and facilitate initiation of psychological and cognitive interventions, which can improve patient quality of life, and warrants further investigation.

Neurocognitive functioning is associated with functional independence in newly diagnosed patients with temporal lobe glioma.

BACKGROUND: Cancer and treatment-related neurocognitive dysfunction has the potential to significantly disrupt the lives of survivors. While neurocognitive functioning is known to predict aspects of patient-reported quality of life in individuals with glioma, little is known regarding the association between neurocognitive functioning and clinician-rated functional independence. METHODS: Newly diagnosed patients with glioma in the left (n = 73; 49% glioblastoma) or right (n = 30; 57% glioblastoma) temporal lobe completed comprehensive neuropsychological testing. Clinicians rated patient functional independence using the Functional Independence Measure (FIM) and Karnofsky Performance Status (KPS) scale. Correlational and regression analyses were conducted to determine relationships between neurocognitive functioning and functional independence. RESULTS: Tests of verbal learning, executive function, and language comprehension were moderately to strongly associated with clinician-rated functional independence, particularly for items pertaining to need for assistance with memory, problem-solving, and language functions. Stepwise linear regression showed that tests of verbal learning, executive functioning, and language comprehension predicted FIM ratings, together accounting for 40% of variance (P < .001). A test of executive functioning also predicted KPS scores and accounted for 19% of variance (P < .001). CONCLUSIONS: In patients with newly diagnosed temporal lobe glioma, neurocognitive functioning is associated with functional independence. Verbal learning, executive functioning, and language comprehension demonstrated the strongest associations across both measures of functional independence. These findings provide support for the ecological validity of neuropsychological assessment by demonstrating the real-world clinical significance of objectively assessed neurocognitive functioning in glioma patients.

Neuropsychological Practice in the Oncology Setting.

Oncology has experienced positive shifts in survival curves for many cancers largely due to the development of earlier diagnostics and better therapeutics. This has increased the visibility and need for survivorship services, including clinical neuropsychology. Patients with cancer frequently experience cognitive dysfunction related to the presence of cancer itself and treatment neurotoxicity. These cognitive difficulties can profoundly impact patient functioning and autonomy with accompanying declines in quality of life. Clinical neuropsychologists are uniquely positioned to evaluate the cognitive and affective sequelae of cancer and treatment and provide interventions and recommendations that can benefit well-being and potentially alter the disease course. Despite increasing recognition of the importance of neuropsychological issues to cancer survivorship, many neuropsychologists have limited training and guidance regarding navigating and implementing services within the oncology setting. This article provides the basic rationale for neuropsychological practice and research activities in oncology, as well as the experience of the Section of Neuropsychology at The University of Texas MD Anderson Cancer Center.

IClinfMRI Software for Integrating Functional MRI Techniques in Presurgical Mapping and Clinical Studies.

Task-evoked and resting-state (rs) functional magnetic resonance imaging (fMRI) techniques have been applied to the clinical management of neurological diseases, exemplified by presurgical localization of eloquent cortex, to assist neurosurgeons in maximizing resection while preserving brain functions. In addition, recent studies have recommended incorporating cerebrovascular reactivity (CVR) imaging into clinical fMRI to evaluate the risk of lesion-induced neurovascular uncoupling (NVU). Although each of these imaging techniques possesses its own advantage for presurgical mapping, a specialized clinical software that integrates the three complementary techniques and promptly outputs the analyzed results to radiology and surgical navigation systems in a clinical format is still lacking. We developed the Integrated fMRI for Clinical Research (IClinfMRI) software to facilitate these needs. Beyond the independent processing of task-fMRI, rs-fMRI, and CVR mapping, IClinfMRI encompasses three unique functions: (1) supporting the interactive rs-fMRI mapping while visualizing task-fMRI results (or results from published meta-analysis) as a guidance map, (2) indicating/visualizing the NVU potential on analyzed fMRI maps, and (3) exporting these advanced mapping results in a Digital Imaging and Communications in Medicine (DICOM) format that are ready to export to a picture archiving and communication system (PACS) and a surgical navigation system. In summary, IClinfMRI has the merits of efficiently translating and integrating state-of-the-art imaging techniques for presurgical functional mapping and clinical fMRI studies.

Accuracy of Presurgical Functional MR Imaging for Language Mapping of Brain Tumors: A Systematic Review and Meta-Analysis.

Purpose To compare functional magnetic resonance (MR) imaging for language mapping (hereafter, language functional MR imaging) with direct cortical stimulation (DCS) in patients with brain tumors and to assess factors associated with its accuracy. Materials and Methods PubMed/MEDLINE and related databases were searched for research articles published between January 2000 and September 2016. Findings were pooled by using bivariate random-effects and hierarchic summary receiver operating characteristic curve models. Meta-regression and subgroup analyses were performed to evaluate whether publication year, functional MR imaging paradigm, magnetic field strength, statistical threshold, and analysis software affected classification accuracy. Results Ten articles with a total of 214 patients were included in the analysis. On a per-patient basis, the pooled sensitivity and specificity of functional MR imaging was 44% (95% confidence interval [CI]: 14%, 78%) and 80% (95% CI: 54%, 93%), respectively. On a per-tag basis (ie, each DCS stimulation site or "tag" was considered a separate data point across all patients), the pooled sensitivity and specificity were 67% (95% CI: 51%, 80%) and 55% (95% CI: 25%, 82%), respectively. The per-tag analysis showed significantly higher sensitivity for studies with shorter functional MR imaging session times (P = .03) and relaxed statistical threshold (P = .05). Significantly higher specificity was found when expressive language task (P = .02), longer functional MR imaging session times (P < .01), visual presentation of stimuli (P = .04), and stringent statistical threshold (P = .01) were used. Conclusion Results of this study showed moderate accuracy of language functional MR imaging when compared with intraoperative DCS, and the included studies displayed significant methodologic heterogeneity. © RSNA, 2017 Online supplemental material is available for this article.

Relationships between neurocognitive functioning, mood, and quality of life in patients with temporal lobe glioma.

OBJECTIVE: While neurocognitive functioning (NCF) and mood disturbance share a relationship with health-related quality of life (HRQOL), few studies have examined relationships between these constructs in glioma patients prior to treatment. METHODS: Newly diagnosed patients with glioma in the left (N = 73; 49% glioblastoma) or right (N = 30; 57% glioblastoma) temporal lobe completed neuropsychological testing and self-report measures of HRQOL (Functional Assessment of Cancer Therapy (FACT)-General and Brain module) and mood (Beck Depression Inventory-Second Edition and State-Trait Anxiety Inventory). RESULTS: Verbal learning and memory, executive function, and language abilities were associated with various HRQOL scales. Stepwise linear regression showed that verbal learning predicted scores on the general well-being scale and brain module, processing speed predicted social well-being scores, and executive functioning predicted functional well-being scores on the FACT. Upper extremity strength also predicted scores on the functional well-being subscale and brain module. Mood was more strongly associated with HRQOL domains than NCF, with depressive symptoms accounting for a large proportion of variance across most subscales. CONCLUSIONS: In patients with temporal lobe glioma, depressive symptoms are strongly related to most aspects of HRQOL but not with NCF. NCF, specifically verbal learning and memory, executive functioning, and processing speed, also show direct relationships with numerous aspects of HRQOL. These findings underscore the importance of multimodal assessment of NCF and mood in this population. Copyright © 2015 John Wiley & Sons, Ltd.