Tumor location and reduction in functional MRI estimates of language laterality

J Neurosurg 135:1674–1684, 2021

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.


Comparison of language cortex reorganization patterns between cerebral arteriovenous malformations and gliomas: a functional MRI study

Comparison of language cortex reorganization patterns between cerebral arteriovenous malformations and gliomas- a functional MRI study

J Neurosurg 122:996–1003, 2015

Cerebral arteriovenous malformations (AVMs) are congenital malformations that may grow in the language cortex but usually do not lead to aphasia. In contrast, language dysfunction is a common presentation for patients with a glioma that involves language areas. The authors attempted to demonstrate the difference in patterns of language cortex reorganization between cerebral AVMs and gliomas by blood oxygen level–dependent (BOLD) functional MRI (fMRI) evaluation.

Methods The authors retrospectively reviewed clinical and imaging data of 63 patients with an unruptured cerebral AVM (AVM group) and 38 patients with a glioma (glioma group) who underwent fMRI. All the patients were right handed, and all their lesions were located in the left cerebral hemisphere. Patients were further categorized into 1 of the 2 following subgroups according to their lesion location: the BA subgroup (overlying or adjacent to the inferior frontal or the middle frontal gyri [the Broca area]) and the WA subgroup (overlying or adjacent to the supramarginal, angular, or superior temporal gyri [the Wernicke area]). Lateralization indices of BOLD signal activations were calculated separately for the Broca and Wernicke areas. Statistical analysis was performed to identify the difference in patterns of language cortex reorganization between the 2 groups.

Results In the AVM group, right-sided lateralization of BOLD signal activations was observed in 23 patients (36.5%), including 6 with right-sided lateralization in the Broca area alone, 12 in the Wernicke area alone, and 5 in both areas. More specifically, in the 34 patients in the AVM-BA subgroup, right-sided lateralization of the Broca area was detected in 9 patients (26.5%), and right-sided lateralization of the Wernicke area was detected in 4 (11.8%); in the 29 patients in the AVM-WA subgroup, 2 (6.9%) had right-sided lateralization of the Broca area, and 13 (44.8%) had right-sided lateralization of the Wernicke area. In the glioma group, 6 patients (15.8%) showed right-sided lateralization of the Wernicke area, including 2 patients in the glioma-BA subgroup and 4 patients in the glioma-WA subgroup. No patient showed right-sided lateralization of the Broca area. Moreover, although the incidence of right-sided lateralization was higher in cases of low-grade gliomas (5 in 26 [19.2%]) than in high-grade gliomas (1 in 12 [8.3%]), no significant difference was detected between them (p = 0.643). Compared with the AVM group, the incidence of aphasia was significantly higher (p < 0.001), and right-sided lateralization of language areas was significantly rarer (p = 0.026) in the glioma group.

Conclusions Right-sided lateralization of BOLD signal activations was observed in patients with a cerebral AVM and in those with a glioma, suggesting that language cortex reorganization may occur with both diseases. However, the potential of reorganization in patients with gliomas seems to be insufficient compared with patients AVMs, which is suggested by clinical manifestations and the fMRI findings. Moreover, this study seems to indicate that in patients with an AVM, a nidus near the Broca area mainly leads to right-sided lateralization of the Broca area, and a nidus near the Wernicke area mainly leads to right-sided lateralization of the Wernicke area.

Subcortical Injury Is an Independent Predictor of Worsening Neurological Deficits Following Awake Craniotomy Procedures


Neurosurgery 72:160–169, 2013

Tailored craniotomies for awake procedures limit cortical exposure. Recently we demonstrated that the identification of eloquent areas increased the risk of postoperative deficits. However, it was not clear whether the observed neurological deficits were caused by proximity of functional cortex to the tumor [cortical injury] or subcortical injury.

OBJECTIVE: We hypothesize that subcortical injury during tumor resection is an important predictor of postoperative neurological deficits compared to cortical injury.

METHODS: A retrospective review of 214 patients undergoing awake craniotomy was carried out in whom preoperative functional magnetic resonance imaging (fMRI) and cortical mapping (CM) were performed. A radiologist blinded to the clinical data reviewed and graded the postoperative changes on diffusion-weighted MR-imaging (DWI).

RESULTS: Of the 40 cases who developed new intraoperative neurological deficit, 36 (90%) occurred during subcortical dissection, 3 (7.5%) during both subcortical and cortical dissection, and 1 (2.5%) during cortical dissection. Neurological dysfunction acquired during subcortical dissection was an independent predictor of postoperative deficits both in the immediate postoperative period (P< .001) and at the 3-month follow-up (P < .001). Significant DWI restriction in the subcortical white matter was predictive of neurological deficits both immediately and at 3 months, P = .011 and P < .001, respectively. New or worsening deficits were seen in 38% of patients; however, at 3 months 13% had a mild persistent neurological deficit.

CONCLUSION: Subcortical injury with significant DWI changes result in postoperative neurological decline despite our efforts to preserve cortical areas of function. This underscores the importance of preserving subcortical fiber tracts during awake craniotomy procedures.

A Detailed Analysis of Functional Magnetic Resonance Imaging in the Frontal Language Area: A Comparative Study With Extraoperative Electrocortical Stimulation

Neurosurgery 69:590–597, 2011 DOI: 10.1227/NEU.0b013e3182181be1

Functional magnetic resonance imaging (fMRI) is a less invasive way of mapping brain functions. The reliability of fMRI for localizing language-related function is yet to be determined.

OBJECTIVE: We performed a detailed analysis of language fMRI reliability by comparing the results of 3-T fMRI with maps determined by extraoperative electrocortical stimulation (ECS).

METHODS: This study was performed on 8 epileptic patients who underwent subdural electrode placement. The tasks performed during fMRI included verb generation, abstract/ concrete categorization, and picture naming. We focused on the frontal lobe, which was effectively activated by these tasks. In extraoperative ECS, 4 tasks were combined to determine the eloquent areas: spontaneous speech, picture naming, reading, and comprehension. We calculated the sensitivity and specificity with different Z score thresholds for each task and appropriate matching criteria. For further analysis, we divided the frontal lobe into 5 areas and investigated intergyrus variations in sensitivity and specificity.

RESULTS: The abstract/concrete categorization task was the most sensitive and specific task in fMRI, whereas the picture naming task detected eloquent areas most efficiently in ECS. The combination of the abstract/concrete categorization task and a 3-mm matching criterion gave the best tradeoff (sensitivity, 83%; specificity, 61%) when the Z score was 2.24. As for intergyrus variation, the posterior inferior frontal gyrus showed the best tradeoff (sensitivity, 91%; specificity, 59%), whereas the anterior middle frontal gyrus had low specificity.

CONCLUSION: Despite different tasks for fMRI and extraoperative ECS, the relatively low specificity might be caused by a fundamental discrepancy between the 2 techniques. Reliability of language fMRI activation might differ, depending on the brain region.