Presurgical language fMRI: Technical practices in epilepsy surgical planning.

Little is known about how language functional MRI (fMRI) is executed in clinical practice in spite of its widespread use. Here we comprehensively documented its execution in surgical planning in epilepsy. A questionnaire focusing on cognitive design, image acquisition, analysis and interpretation, and practical considerations was developed. Individuals responsible for collecting, analyzing, and interpreting clinical language fMRI data at 63 epilepsy surgical programs responded. The central finding was of marked heterogeneity in all aspects of fMRI. Most programs use multiple tasks, with a fifth routinely using 2, 3, 4, or 5 tasks with a modal run duration of 5 min. Variants of over 15 protocols are in routine use with forms of noun-verb generation, verbal fluency, and semantic decision-making used most often. Nearly all aspects of data acquisition and analysis vary markedly. Neither of the two best-validated protocols was used by more than 10% of respondents. Preprocessing steps are broadly consistent across sites, language-related blood flow is most often identified using general linear modeling (76% of respondents), and statistical thresholding typically varies by patient (79%). The software SPM is most often used. fMRI programs inconsistently include input from experts with all required skills (imaging, cognitive assessment, MR physics, statistical analysis, and brain-behavior relationships). These data highlight marked gaps between the evidence supporting fMRI and its clinical application. Teams performing language fMRI may benefit from evaluating practice with reference to the best-validated protocols to date and ensuring individuals trained in all aspects of fMRI are involved to optimize patient care.

Role of the Wada test and functional magnetic resonance imaging in preoperative mapping of language and memory: two atypical cases.

The Wada test is an invasive procedure used to determine cerebral memory and language dominance as well as risk of cognitive deficits following neurosurgery. However, the potential risks of Wada testing have led some to consider foregoing Wada testing in candidates for resective epilepsy surgery with right hemispheric seizure onset. We present two atypical cases in which the Wada test showed unexpected memory and language lateralization. These cases underscore the importance of functional magnetic resonance in which imaging and Wada examination in right-handed individuals even when the lesion would not suggest atypical language representation.

Grey matter reshaping of language-related regions depends on tumor lateralization.

A brain tumor in the left hemisphere can decrease language laterality as assessed with fMRI. However, it remains unclear whether or not this decreased language laterality is associated with a structural reshaping of the grey matter, particularly within the language network. Here, we examine if the disruption of language hubs exclusively affects macrostructural properties of contralateral homologues (as suggested by previous research), or whether it affects both hemispheres. This study uses voxel-based morphometry applied to high-resolution MR T1-weighted MPRAGE images from 31 adult patients left-dominant for language. Eighteen patients had brain tumors in the left hemisphere, and 13 had tumors in the right hemisphere. A cohort of 71 healthy individuals matched on age and sex was used as a baseline. We defined 10 ROIs per hemisphere known to subserve language function. Two separate repeated-measures ANOVAs were conducted with the volume per region as the dependent variables. For the patients, tumor lateralization (right versus left) served as a between-subject factor. The current study demonstrated that the presence of a brain tumor generates a global volumetric change affecting left language regions and their contralateral homologues. These changes are mediated by the lateralization of the lesion. Our findings suggest that compensatory functional mechanisms are supported by the rearrangement of the grey matter, although future longitudinal research should determine the temporal course of such changes.

Grey Matter Reshaping of Language-Related Regions Depends on Tumor Lateralization.

A brain tumor in the left hemisphere can decrease language laterality as assessed through fMRI. However, it remains unclear whether or not this decreased language laterality is associated with a structural reshaping of the grey matter, particularly within the language network. Here, we examine if the disruption of the language hubs exclusively affects the macrostructural properties of the contralateral homologues or whether it affects both hemispheres. This study uses voxel-based morphometry applied to high-resolution MR T1-weighted MPRAGE images from 31 adult patients' left hemisphere, which is dominant for language. Eighteen patients had brain tumors in the left hemisphere, and thirteen had tumors in the right hemisphere. A cohort of 71 healthy individuals matched with respect to age and sex was used as a baseline. We defined 10 ROIs per hemisphere involved in language function. Two separate repeated-measure ANOVAs were conducted with the volume per region as the dependent variable. For the patients, tumor lateralization (right versus left) served as a between-subject factor. The current study demonstrated that the presence of a brain tumor generates global volumetric changes affecting the left language regions and their contralateral homologues. These changes are mediated by the lateralization of the lesion. Our findings suggest that functional mechanisms are supported by the rearrangement of the grey matter.

Organizing Variables Affecting fMRI Estimates of Language Dominance in Patients with Brain Tumors.

Numerous variables can affect the assessment of language dominance using presurgical functional magnetic resonance (fMRI) in patients with brain tumors. This work organizes the variables into confounding and modulating factors. Confounding factors give the appearance of changed language dominance. Most confounding factors are fMRI-specific and they can substantially disrupt the evaluation of language dominance. Confounding factors can be divided into two categories: tumor-related and fMRI analysis. The tumor-related confounds further subdivide into tumor characteristics (e.g., tumor grade) and tumor-induced conditions (aphasia). The fMRI analysis confounds represent technical aspects of fMRI methods (e.g., a fixed versus an individual threshold). Modulating factors can modify language dominance without confounding it. They are not fMRI-specific, and they can impact language dominance both in healthy individuals and neurosurgical patients. The effect of most modulating factors on fMRI language dominance is smaller than that of confounding factors. Modulating factors include demographics (e.g., age) and linguistic variables (e.g., early bilingualism). Three cases of brain tumors in the left hemisphere are presented to illustrate how modulating confounding and modulating factors can impact fMRI estimates of language dominance. Distinguishing between confounding and modulating factors can help interpret the results of presurgical language mapping with fMRI.

General principles governing the amount of neuroanatomical overlap between languages in bilinguals.

The literature has identified many important factors affecting the extent to which languages in bilinguals rely on the same neural populations in the specific brain region. The factors include the age of acquisition of the second language (L2), proficiency level of the first language (L1) and L2, and the amount of language exposure, among others. What is lacking is a set of global principles that explain how the many factors relate to the degree to which languages overlap neuroanatomically in bilinguals. We are offering a set of such principles that together account for the numerous sources of data that have been examined individually but not collectively: (1) the principle of acquisition similarity between L1 and L2, (2) the principle of linguistic similarity between L1 and L2, and (3) the principle of cognitive control and effort. Referencing the broad characteristics of language organization in bilinguals, as presented by the principles, can provide a roadmap for future clinical and basic science research.

Prior Neurosurgery Decreases fMRI Estimates of Language Laterality in Patients with Gliomas within Anterior Language Sites.

The impact of previous surgery on the assessment of language dominance with preoperative fMRI remains inconclusive in patients with recurrent brain tumors. Samples in this retrospective study included 17 patients with prior brain surgery and 21 patients without prior surgery (38 patients total; mean age 43.2, SD = 11.9; 18 females; seven left-handed). All the patients were left language dominant, as determined clinically. The two samples were matched on 10 known confounds, including, for example, tumor laterality and location (all tumors affected Brodmann areas 44/45/47). We calculated fMRI language dominance with laterality indices using a whole-brain and region of interest approach (ROI; Broca's and Wernicke's area). Patients with prior surgery had decreased fMRI language dominance (p = 0.03) with more activity in the right hemisphere (p = 0.03) than patients without surgery. Patients with prior brain surgery did not display less language activity in the left hemisphere than patients without surgery. These results were replicated using an ROI approach in the affected Broca's area. Further, we observed no differences between our samples in the unaffected Wernicke's area. In sum, prior brain surgery affecting Broca's area could be a confounding factor that needs to be considered when evaluating fMRI language dominance.

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

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

Factors Modifying the Amount of Neuroanatomical Overlap between Languages in Bilinguals-A Systematic Review of Neurosurgical Language Mapping Studies.

Neurosurgery on individuals with lesions around language areas becomes even more complicated when the patient is bilingual. It is thus important to understand the principles that predict the likelihood of convergent versus separate neuroanatomical organization of the first (L1) and the second language (L2) in these individuals. We reviewed all English-language publications on neurosurgical language mapping in bilinguals before January 2020 in three databases (e.g., PubMed). Our search yielded 28 studies with 207 participants. The reviewed data suggest several principles of language organization in bilingual neurosurgical patients: (1) separate cortical areas uniquely dedicated to each language in both anterior and posterior language sites are the rule rather than occasional findings, (2) In cases where there was a convergent neuroanatomical representation for L1 and L2, two factors explained the overlap: an early age of L2 acquisition and a small linguistic distance between L1 and L2 and (3) When L1 and L2 diverged neuroanatomically, more L1-specific sites were identified for early age of L2 acquisition, high L2 proficiency and a larger linguistic distance. This work provides initial evidence-based principles predicting the likelihood of converging versus separate neural representations of L1 and L2 in neurosurgical patients.

Lateralizing language function with pre-operative functional magnetic resonance imaging in early proficient bilingual patients.

Research on bilinguals with brain lesions is complicated by high patient variability, making it difficult to find well-matched controls. We benefitted from a database of over 700 patients and conducted an analysis of pre-operative functional magnetic resonance imaging data to assess language dominance in 25 early, highly proficient Spanish-English bilinguals, and 25 carefully matched monolingual controls. Our results showed that early bilingualism is associated with greater bilateral hemispheric involvement, and monolingualism is associated with stronger left hemisphere lateralization (p=0.009). The bilinguals showed more pronounced right hemisphere activation (p=0.008). Although language dominance values were concordant in the bilingual group, there were a few (12%) atypical cases with different lateralization patterns in L1 and L2. Finally, we found distinct areas of activity in first and second language within the language network, in addition to regions of convergence. These data underscore the need to map all languages proficiently spoken by surgical candidates.

Language system organization in a quadrilingual with a brain tumor: Implications for understanding of the language network.

In pre-neurosurgery language mapping it is critical to identify language-specific regions in multilingual speakers. We conducted pre-operative functional magnetic resonance imaging, and intraoperative language mapping in the unique case of a highly proficient quadrilingual with a left frontal brain tumor who acquired her second language at age 5, and her third and fourth languages at 15. We found a predominantly different organization in each language with only a few areas shared by all 4 languages. Contrary to existing evidence, impairment across languages was not related to age of acquisition, amount of exposure, or language similarity. This case suggests that the functional structure of the language system may be highly idiosyncratic in multilingual individuals and supports detailed study in this group to inform neurocognitive models of language.