Differential contribution of language and executive functioning to verbal fluency performance in glioma patients.

Glioma patients often suffer from deficits in language and executive functioning. Performance in verbal fluency (generating words within one minute according to a semantic category-category fluency, or given letter-letter fluency) is typically impaired in this patient group. While both language and executive functioning play a role in verbal fluency, the relative contribution of both domains remains unclear. We aim to retrospectively investigate glioma patients' performance on verbal and nonverbal fluency and to explore the influence of language and executive functioning on verbal fluency. Sixty-nine adults with gliomas in eloquent areas underwent a neuropsychological test battery (verbal fluency, nonverbal fluency, language, and executive functioning tests) before surgery (T1) and a subgroup of 31 patients also at three (T2) and twelve months (T3) after surgery. Preoperatively, patients were impaired in all verbal fluency tasks and dissociations were found based on tumour location. In contrast, nonverbal fluency was intact. Different language and executive functioning tests predicted performance on category fluency animals and letter fluency, while no significant predictors for category fluency professions were found. The longitudinal results indicated that category fluency professions deteriorated after surgery (T1-T2, T1-T3) and that nonverbal fluency improved after surgery (T1-T3, T2-T3). Verbal fluency performance can provide information on different possible underlying deficits in language and executive functioning in glioma patients, depending on verbal fluency task selection. Efficient task (order) selection can be based on complexity. Category fluency professions can be selected to detect more permanent long-term deficits.

Localization patterns of speech and language errors during awake brain surgery: a systematic review.

Awake craniotomy with direct electrical stimulation (DES) is the standard treatment for patients with eloquent area gliomas. DES detects speech and language errors, which indicate functional boundaries that must be maintained to preserve quality of life. During DES, traditional object naming or other linguistic tasks such as tasks from the Dutch Linguistic Intraoperative Protocol (DuLIP) can be used. It is not fully clear which speech and language errors occur in which brain locations. To provide an overview and to update DuLIP, a systematic review was conducted in which 102 studies were included, reporting on speech and language errors and the corresponding brain locations during awake craniotomy with DES in adult glioma patients up until 6 July 2020. The current findings provide a crude overview on language localization. Even though subcortical areas are in general less often investigated intraoperatively, still 40% out of all errors was reported at the subcortical level and almost 60% at the cortical level. Rudimentary localization patterns for different error types were observed and compared to the dual-stream model of language processing and the DuLIP model. While most patterns were similar compared to the models, additional locations were identified for articulation/motor speech, phonology, reading, and writing. Based on these patterns, we propose an updated DuLIP model. This model can be applied for a more adequate "location-to-function" language task selection to assess different linguistic functions during awake craniotomy, to possibly improve intraoperative language monitoring. This could result in a better postoperative language outcome in the future.

DIMA-fr: a French adaptation and standardization of the Dutch Diagnostic Instrument for Mild Aphasia (DIMA-nl).

The Dutch Diagnostic Instrument for Mild Aphasia (DIMA-nl) is a standardized battery recently created for evaluating the language performance of patients during the perioperative period of glioma surgery. Our aim was to establish normative data for the DIMA-fr, a French version of the DIMA-nl. The DIMA-nl was first adapted to French. The 14 subtasks of the DIMA-fr were then administered to 391 participants recruited from the general French population. The effects of sex, age and level of education were determined by analysis of variance (ANOVA). Normative data were computed as means, medians, standard deviations and percentiles. Our results demonstrated that age and level of education had an effect on the performance of all subtests but not sex. We thus stratified the norms into four different groups: (i) 18-69 years-old with Baccalauréat (Bac, the French High School Diploma) (n = 246); (ii) 18-69 years-old without Bac (n = 70); (iii) >70 years-old with Bac (n = 48); (iv) >70 years-old without Bac (n = 27). The DIMA-fr is thus the first standardized French battery of tests to specifically assess language during the perioperative period of awake glioma surgery. However, to be used in the clinic, the DIMA-fr must now be validated in patients. The DIMA, which is currently standardized in several languages, could become a reference tool for international studies.

Dutch Diagnostic Instrument for Mild Aphasia (DIMA): standardisation and a first clinical application in two brain tumour patients.

Brain tumour patients with mild language disturbances are typically underdiagnosed due to lack of sensitive tests leading to negative effects in daily communicative and social life. We aim to develop a Dutch standardised test-battery, the Diagnostic Instrument for Mild Aphasia (DIMA) to detect characteristics of mild aphasia at the main linguistic levels phonology, semantics and (morpho-)syntax in production and comprehension. We designed 4 DIMA subtests: 1) repetition (words, non-words, compounds and sentences), 2) semantic odd-picture-out (objects and actions), 3) sentence completion and 4) sentence judgment (accuracy and reaction time). A normative study was carried out in a healthy Dutch-speaking population (N = 211) divided into groups of gender, age and education. Clinical application of DIMA was demonstrated in two brain tumour patients (glioma and meningioma). Standard language tests were also administered: object naming, verbal fluency (category and letter), and Token Test. Performance was at ceiling on all sub-tests, except semantic odd-picture-out actions, with an effect of age and education on most subtests. Clinical application DIMA: repetition was impaired in both cases. Reaction time in the sentence judgment test (phonology and syntax) was impaired (not accuracy) in one patient. Standard language tests: category fluency was impaired in both cases and object naming in one patient. The Token Test was not able to detect language disturbances in both cases. DIMA seems to be sensitive to capture mild aphasic deficits. DIMA is expected to be of great potential for standard assessment of language functions in patients with also other neurological diseases than brain tumours.

Augmented reality for the virtual dissection of white matter pathways.

BACKGROUND: The human white matter pathway network is complex and of critical importance for functionality. Thus, learning and understanding white matter tract anatomy is important for the training of neuroscientists and neurosurgeons. The study aims to test and evaluate a new method for fiber dissection using augmented reality (AR) in a group which is experienced in cadaver white matter dissection courses and in vivo tractography. METHODS: Fifteen neurosurgeons, neurolinguists, and neuroscientists participated in this questionnaire-based study. We presented five cases of patients with left-sided perisylvian gliomas who underwent awake craniotomy. Diffusion tensor imaging fiber tracking (DTI FT) was performed and the language-related networks were visualized separated in different tracts by color. Participants were able to virtually dissect the prepared DTI FTs using a spatial computer and AR goggles. The application was evaluated through a questionnaire with answers from 0 (minimum) to 10 (maximum). RESULTS: Participants rated the overall experience of AR fiber dissection with a median of 8 points (mean ± standard deviation 8.5 ± 1.4). Usefulness for fiber dissection courses and education in general was rated with 8 (8.3 ± 1.4) and 8 (8.1 ± 1.5) points, respectively. Educational value was expected to be high for several target audiences (student: median 9, 8.6 ± 1.4; resident: 9, 8.5 ± 1.8; surgeon: 9, 8.2 ± 2.4; scientist: 8.5, 8.0 ± 2.4). Even clinical application of AR fiber dissection was expected to be of value with a median of 7 points (7.0 ± 2.5). CONCLUSION: The present evaluation of this first application of AR for fiber dissection shows a throughout positive evaluation for educational purposes.

Changes in language white matter tract microarchitecture associated with cognitive deficits in patients with presumed low-grade glioma.

OBJECTIVEThe authors conducted a study to determine whether cognitive functioning of patients with presumed low-grade glioma is associated with white matter (WM) tract changes.METHODSThe authors included 77 patients with presumed low-grade glioma who underwent awake surgery between 2005 and 2013. Diffusion tensor imaging with deterministic tractography was performed preoperatively to identify the arcuate, inferior frontooccipital, and uncinate fasciculi and to obtain the mean fractional anisotropy (FA) and mean diffusivity per tract. All patients were evaluated preoperatively using an extensive neuropsychological protocol that included assessments of the language, memory, and attention/executive function domains. Linear regression models were used to analyze each cognitive domain and each diffusion tensor imaging metric of the 3 WM tracts.RESULTSSignificant correlations (corrected for multiple testing) were found between FA of the arcuate fasciculus and results of the repetition test for the language domain (ß = 0.59, p < 0.0001) and between FA of the inferior frontooccipital fasciculus and results of the imprinting test for the memory domain (ß = -0.55, p = 0.002) and the attention test for the attention and executive function domain (ß = -0.62, p = 0.006).CONCLUSIONSIn patients with glioma, language deficits in repetition of speech, imprinting, and attention deficits are associated with changes in the microarchitecture of the arcuate and inferior frontooccipital fasciculi.

Spontaneous speech in patients with gliomas in eloquent areas: Evaluation until 1 year after surgery.

OBJECTIVE: Glioma patients often complain about problems in daily conversation with a negative impact on quality of life. Disorders in standardized language tests (e.g. naming and fluency), are frequently observed. Most studies claim recovery of language functions within 3 months. However, long-term effects of surgery on spontaneous speech remain unknown. PATIENTS AND METHODS: Eighteen glioma patients were compared to healthy controls in spontaneous speech variables: Type Token Ratio (TTR), Mean Length of Utterance words (MLUw), Incomplete Sentences, Self-corrections and Repetitions. Boston Naming Test (BNT) and Category Fluency (CF) were also assessed. We compared: pre- and 3 months postoperatively (T1-T2), 3 months and 1 year postoperatively (T2-T3), pre- and 1 year postoperatively (T1-T3). Correlations were computed between deviating variables and BNT/CF, tumor localization, and tumor grade. RESULTS: Patients had deficits in Incomplete sentences (T1, T2, T3), TTR (T2,T3), MLUw (T3) and Self-corrections (T2). Between T1-T2 no decline was present. Between T2-T3 and T1-T3, there was a decrease of MLUw, Self-corrections and Repetitions and an increase of Incomplete Sentences, BNT and CF were impaired (T1, T2, T3) without differences between test-moments. Most spontaneous speech variables did not correlate with standardized tests. Tumor localization and grade had no influence on spontaneous speech. CONCLUSION: Glioma patients showed impaired spontaneous speech combined with naming and fluency deficits. Surgery appeared to have deteriorated the quality of spontaneous speech until long-term but not the performance at test-level. Hence, spontaneous speech has an added value to standardized tests for diagnosis of language impairments.

Differential Effects of Awake Glioma Surgery in "Critical" Language Areas on Cognition: 4 Case Studies.

Awake surgery with electrocorticosubcortical stimulation is the golden standard treatment for gliomas in eloquent areas. Preoperatively, mostly mild cognitive disturbances are observed with postoperative deterioration. We describe pre- and postoperative profiles of 4 patients (P1-P4) with gliomas in "critical" language areas ("Broca," "Wernicke," and the arcuate fasciculus) undergoing awake surgery to get insight into the underlying mechanism of neuroplasticity. Neuropsychological examination was carried out preoperatively (at T1) and postoperatively (at T2, T3). At T1, cognition of P1 was intact and remained stable. P2 had impairments in all cognitive domains at T1 with further deterioration at T2 and T3. At T1, P3 had impairments in memory and executive functions followed by stable recovery. P4 was intact at T1, followed by a decline in a language test at T2 and recovery at T3. Intraoperatively, in all patients language positive sites were identified. Patients with gliomas in "critical" language areas do not necessarily present cognitive disturbances. Surgery can either improve or deteriorate (existing) cognitive impairments. Several factors may underlie the plastic potential of the brain, for example, corticosubcortical networks and tumor histopathology. Our findings illustrate the complexity of the underlying mechanism of neural plasticity and provide further support for a "hodotopical" viewpoint.

Glioma surgery in eloquent areas: can we preserve cognition?

BACKGROUND: Cognitive preservation is crucial in glioma surgery, as it is an important aspect of daily life functioning. Several studies claimed that surgery in eloquent areas is possible without causing severe cognitive damage. However, this conclusion was relatively ungrounded due to the lack of extensive neuropsychological testing in homogenous patient groups. In this study, we aimed to elucidate the short-term and long-term effects of glioma surgery on cognition by identifying all studies who conducted neuropsychological tests preoperatively and postoperatively in glioma patients. METHODS: We systematically searched the electronical databases Embase, Medline OvidSP, Web of Science, PsychINFO OvidSP, PubMed, Cochrane, Google Scholar, Scirius and Proquest aimed at cognitive performance in glioma patients preoperatively and postoperatively. RESULTS: We included 17 studies with tests assessing the cognitive domains: language, memory, attention, executive functions and/or visuospatial abilities. Language was the domain most frequently examined. Immediately postoperatively, all studies except one, found deterioration in one or more cognitive domains. In the longer term (3-6/6-12 months postoperatively), the following tests showed both recovery and deterioration compared with the preoperative level: naming and verbal fluency (language), verbal word learning (memory) and Trailmaking B (executive functions). CONCLUSIONS: Cognitive recovery to the preoperative level after surgery is possible to a certain extent; however, the results are too arbitrary to draw definite conclusions and not all studies investigated all cognitive domains. More studies with longer postoperative follow-up with tests for cognitive change are necessary for a better understanding of the conclusive effects of glioma surgery on cognition.

Dynamic aphasia following low-grade glioma surgery near the supplementary motor area: a selective spontaneous speech deficit.

We describe a patient (KO) with reduced spontaneous speech, resembling dynamic aphasia, after awake glioma surgery in the proximity of the supplementary motor area. Naming, repetition, and comprehension were intact. He was tested with an extensive neuropsychological test-battery and a protocol for dynamic aphasia at 1 year. He presented with postoperative reduced spontaneous speech and selective executive function deficits. Most language recovery took place at 3 months postoperatively, whereas the executive functions improved between 3 months and 1 year. Results suggest that resection near the supplementary motor area could increase the risk of cognitive disturbances at long term, especially language.

Long-term evaluation of cognition after glioma surgery in eloquent areas.

Preservation of cognition is an important outcome measure in eloquent area glioma surgery. Glioma patients may have pre-operative deficits in one or more cognitive domains which could deteriorate post-operatively. It is assumed that these impairments recover within 3 months; some studies however, still detected cognitive decline. Longer follow-up is necessary to elucidate the conclusive effects of surgery. 45 patients with gliomas (low- and high-grade, but without contrast enhancement at diagnosis) in eloquent areas were assessed pre-operatively, 3 months and 1 year post-operatively with a neuropsychological test-protocol. Patients' performance was compared to normal population and between test-moments. Univariate analyses were performed between cognitive change and tumor-characteristics (localization, grade, volume, extent of resection [EOR]) and treatment-related factors (radio-/chemotherapy). Pre- and post-operatively, impairments were found in all cognitive domains; language, memory, attention and executive functions (p < 0.05). Post-operatively, permanent improvement was observed on a memory test (verbal recall: t = -1.931, p = 0.034), whereas deterioration was found on a language test (category fluency: t = 2.517, p = 0.030). Between 3 months and 1 year, patients improved on 2 language tests (naming: t = -2.781, p = 0.026 and letter fluency: t = -1.975, p = 0.047). There was no influence of tumor- or treatment-related factors on cognitive change. The findings underline the importance of cognitive testing at longer term post-operatively, as cognitive recovery took longer than 3 months, especially within the language domain. However, this longitudinal follow-up study showed that glioma surgery is possible without major long-term damage of cognitive functions. Tumor characteristics and EOR are no additional risk factors for cognitive outcome.

Spontaneous speech of patients with gliomas in eloquent areas before and early after surgery.

BACKGROUND: Glioma patients often complain about problems in daily conversation. A detailed spontaneous speech analysis could provide more insight in these communicative problems; no previous studies are reported. OBJECTIVE: To select sensitive parameters in spontaneous speech pre- and post-operatively in patients with gliomas in eloquent areas. METHODS: We included 27 patients and 21 healthy controls. In addition to a naming and category fluency test, spontaneous speech was collected 1 month pre-operatively and 3 months post-operatively, and analysed with the variables: Self-corrections, Repetitions, Lexical Diversity, Incomplete Sentences and Mean Length of Utterance (MLUw). A correlation analysis was performed between the linguistic variables and tumour characteristics (grade, localisation and volume), treatment related factors, and between the linguistic variables and the language tasks. RESULTS: Pre-operatively, patients produced more Incomplete Sentences than the controls (p < 0.001). Post-operatively, patients' utterance length (MLUw) (p < 0.05) was also deviant. The quality of the spontaneous speech was influenced by tumour grade and localisation. There was no influence of tumour volume or treatment-related factors. Pre- and post-operatively, patients' performance on the naming and the fluency task deviated from normal (p < 0.001). The majority of the linguistic variables did not correlate with the language tasks, pointing to a measurement of distinct linguistic aspects. CONCLUSION: Pre- and post-operatively there was a disorder in naming, category fluency and spontaneous speech, partly influenced by tumour characteristics. A spontaneous speech analysis appeared to be a valuable addition to standardised language tasks. Both measurements are important tools to obtain a complete linguistic profile.

Cognitive functioning early after surgery of gliomas in eloquent areas.

OBJECT: Patients with gliomas frequently have cognitive deficits, and surgery can exacerbate these deficits. Preoperative assessment is therefore crucial in patients undergoing surgery for glioma in eloquent areas, because the proximity of functional areas increases the risk of permanent postoperative cognitive disturbances. Although pre- and postoperative language and motor function in patients with glioma have been investigated frequently, data on good cognition studies are scarce. Most studies have focused on clinical neurological functioning or have only used brief neurological instruments. The authors investigated whether surgery for glioma in eloquent areas influences cognition early after surgery, by using an elaborate test protocol. METHODS: Twenty-eight patients with gliomas of the left hemisphere in language and nonlanguage areas were assessed before and 3 months after surgery with a comprehensive neuropsychological test protocol. The authors performed a correlation analysis between change in cognitive performance and tumor characteristics (that is, location, volume, pathological features, and histological grade) and between cognitive change and treatment-related factors (the extent of the resection and postoperative treatment with chemo- and radiotherapy). RESULTS: Both pre- and postoperatively, the mean performance of the patients was worse than the performance of the normal population in the language domain, the memory domain, and the executive functions (p < 0.05). Postoperatively, a decline was found in the language domain (t = 2.34, p = 0.027) and in the executive functions (t = 2.45, p = 0.022). However, cognitive change postsurgery was influenced by the location of the tumor; the decrease of cognitive score in the language domain was only observed in patients with tumors in or close to language areas (t = 2.33, p = 0.029). No effect on cognitive change was found for the other tumor characteristics and treatment-related factors. CONCLUSIONS: This study underlines the importance of the use of a neuropsychological test protocol before and after surgery in patients with glioma, because several tasks in the domains of language, memory, and executive functions appeared to deteriorate after surgery. Tumor resection in language areas increases the risk of cognitive deficits in the language domain postoperatively.