Diffuse glioma-induced structural reorganization in close association with preexisting syntax-related networks.

Glioma in the left frontal cortex has been reported to cause agrammatic comprehension and induce global functional connectivity alterations within the syntax-related networks. However, it remains unclear to what extent the structural reorganization is affected by preexisting syntax-related networks. We examined 28 patients with a diffuse glioma in the left hemisphere and 23 healthy participants. Syntactic abilities were assessed by a picture-sentence matching task with various sentence types. The lesion responsible for agrammatic comprehension was identified by region-of-interest-based lesion-symptom mapping (RLSM). Cortical structural alterations were examined by surface-based morphometry (SBM), in which the cortical thickness and fractal dimension were measured with three-dimensional magnetic resonance imaging (MRI). Fiber tracking on the human population-averaged diffusion MRI template was performed to examine whether the cortical structural alterations were associated with the syntax-related networks. The RLSM revealed associations between agrammatic comprehension and a glioma in the posterior limb of the left internal capsule. The SBM demonstrated that decreased cortical thickness and/or increased complexity of the right posterior insula were associated not only with agrammatic comprehension of the patients but also with the syntactic abilities of healthy participants. The fiber tracking revealed that the route between these two regions was anatomically integrated into the preexisting syntax-related networks previously identified. These results suggest a potential association between agrammatic comprehension in patients with diffuse glioma and structural variations in specific tracts and cortical regions, which may be closely related to the syntax-related networks.

Differential Effects of a Left Frontal Glioma on the Cortical Thickness and Complexity of Both Hemispheres.

Glioma is a type of brain tumor that infiltrates and compresses the brain as it grows. Focal gliomas affect functional connectivity both in the local region of the lesion and the global network of the brain. Any anatomical changes associated with a glioma should thus be clarified. We examined the cortical structures of 15 patients with a glioma in the left lateral frontal cortex and compared them with those of 15 healthy controls by surface-based morphometry. Two regional parameters were measured with 3D-MRI: the cortical thickness (CT) and cortical fractal dimension (FD). The FD serves as an index of the topological complexity of a local cortical surface. Our comparative analyses of these parameters revealed that the left frontal gliomas had global effects on the cortical structures of both hemispheres. The structural changes in the right hemisphere were mainly characterized by a decrease in CT and mild concomitant decrease in FD, whereas those in the peripheral regions of the glioma (left hemisphere) were mainly characterized by a decrease in FD with relative preservation of CT. These differences were found irrespective of tumor volume, location, or grade. These results elucidate the structural effects of gliomas, which extend to the distant contralateral regions.

Task-Induced Functional Connectivity of the Syntax-Related Networks for Patients with a Cortical Glioma.

Analysis of the functional connectivity has enabled understanding of the cortical networks. In the present study, we used a picture-sentence matching task to introduce syntactically harder conditions, and clarified 3 major points. First, patients with a glioma in the lateral premotor cortex/inferior frontal gyrus or in other cortical regions showed much weaker activations than controls, especially in the left inferior frontal gyrus. Moreover, the error rates under the harder conditions were much higher for these patients. Secondly, syntactic loads induced selective connectivity with enhancement and suppression, consistently for both patients and controls. More specifically, the local connectivity was enhanced among the 3 syntax-related networks within the left frontal cortex, while the global connectivity of both dorsal and ventral pathways was suppressed. In addition, the exact reproducibility of r-values across the control and patient groups was remarkable, since under easier conditions alone, connectivity patterns for the patients were completely unmatched with those for the controls. Thirdly, we found an additional syntax-related network, further confirming the intergroup similarity of task-induced functional connectivity. These results indicate that functional connectivity of agrammatic patients is mostly preserved regardless of a glioma, and that the connectivity can change dynamically and systematically according to syntactic loads.

Difficulty in identification of the frontal language area in patients with dominant frontal gliomas that involve the pars triangularis.

OBJECTIVE Identification of language areas using functional brain mapping is sometimes impossible using current methods but essential to preserve language function in patients with gliomas located within or near the frontal language area (FLA). However, the factors that influence the failure to detect language areas have not been elucidated. The present study evaluated the difficulty in identifying the FLA in dominant-side frontal gliomas that involve the pars triangularis (PT) to determine the factors that influenced failed positive language mapping. METHODS Awake craniotomy was performed on 301 patients from April 2000 to October 2013 at Tokyo Women's Medical University. Recurrent cases were excluded, and patients were also excluded if motor mapping indicated their glioma was in or around the motor area on the dominant or nondominant side. Eighty-two consecutive cases of primary frontal glioma on the dominant side were analyzed for the present study. MRI was used for all patients to evaluate whether tumors involved the PT and to perform language functional mapping with a bipolar electrical stimulator. Eighteen of 82 patients (mean age 39 ± 13 years) had tumors that showed involvement of the PT, and the detailed characteristics of these 18 patients were examined. RESULTS The FLA could not be identified with intraoperative brain mapping in 14 (17%) of 82 patients; 11 (79%) of these 14 patients had a tumor involving the PT. The negative response rate in language mapping was only 5% in patients without involvement of the PT, whereas this rate was 61% in patients with involvement of the PT. Univariate analyses showed no significant correlation between identification of the FLA and sex, age, histology, or WHO grade. However, failure to identify the FLA was significantly correlated with involvement of the PT (p < 0.0001). Similarly, multivariate analyses with the logistic regression model showed that only involvement of the PT was significantly correlated with failure to identify the FLA (p < 0.0001). In 18 patients whose tumors involved the PT, only 1 patient had mild preoperative dysphasia. One week after surgery, language function worsened in 4 (22%) of 18 patients. Six months after surgery, 1 (5.6%) of 18 patients had a persistent mild speech deficit. The mean extent of resection was 90% ± 7.1%. Conclusions Identification of the FLA can be difficult in patients with frontal gliomas on the dominant side that involve the PT, but the positive mapping rate of the FLA was 95% in patients without involvement of the PT. These findings are useful for establishing a positive mapping strategy for patients undergoing awake craniotomy for the treatment of frontal gliomas on the dominant side. Thoroughly positive language mapping with subcortical electrical stimulation should be performed in patients without involvement of the PT. More careful continuous neurological monitoring combined with subcortical electrical stimulation is needed when removing dominant-side frontal gliomas that involve the PT.

Left frontal glioma induces functional connectivity changes in syntax-related networks.

BACKGROUND: A glioma leads to a global loss of functional connectivity among multiple regions. However, the relationships between performance/activation changes and functional connectivity remain unclear. Our previous studies (Brain 137:1193-1212; Brain Lang 110:71-80) have shown that a glioma in the left lateral premotor cortex or the opercular/triangular parts of the left inferior frontal gyrus causes agrammatic comprehension accompanied by abnormal activations in 14 syntax-related regions. We have also confirmed that a glioma in the other left frontal regions does not affect task performances and activation patterns. RESULTS: By a partial correlation method for the time-series functional magnetic resonance imaging data, we analyzed the functional connectivity in 21 patients with a left frontal glioma. We observed that almost all of the functional connectivity exhibited chaotic changes in the agrammatic patients. In contrast, some functional connectivity was preserved in an orderly manner in the patients who showed normal performances and activation patterns. More specifically, these latter patients showed normal connectivity between the left fronto-parietal regions, as well as normal connectivity between the left triangular and orbital parts of the left inferior frontal gyrus. CONCLUSIONS: Our results indicate that these pathways are most crucial among the syntax-related networks. Both data from the activation patterns and functional connectivity, which are different in temporal domains, should thus be combined to assess any behavioral deficits associated with brain abnormalities.

[Three neural networks that support syntactic processing in language].

Elucidation of language disorders is one of the fundamental issues in clinical neuroscience. We used magnetic resonance imaging and a syntactic task in Japanese to examine the behavior and brain structures of patients with a left frontal glioma. We successfully showed that they had different types of language disorders (particularly agrammatic comprehension) dependent on the location of the glioma. Moreover, we describe three neural networks that support syntactic processing, including an extensive network within the cerebellum and both hemispheres of the brain.

Intraoperative cortico-cortical evoked potentials for the evaluation of language function during brain tumor resection: initial experience with 13 cases.

OBJECTIVES: The objective in the present study was to evaluate the usefulness of cortico-cortical evoked potentials (CCEP) monitoring for the intraoperative assessment of speech function during resection of brain tumors. METHODS: Intraoperative monitoring of CCEP was applied in 13 patients (mean age 34 ± 14 years) during the removal of neoplasms located within or close to language-related structures in the dominant cerebral hemisphere. For this purpose strip electrodes were positioned above the frontal language area (FLA) and temporal language area (TLA), which were identified with direct cortical stimulation and/or preliminary mapping with the use of implanted chronic subdural grid electrodes. The CCEP response was defined as the highest observed negative peak in either direction of stimulation. In 12 cases the tumor was resected during awake craniotomy. RESULTS: An intraoperative CCEP response was not obtained in one case because of technical problems. In the other patients it was identified from the FLA during stimulation of the TLA (7 cases) and from the TLA during stimulation of the FLA (5 cases), with a mean peak latency of 83 ± 15 msec. During tumor resection the CCEP response was unchanged in 5 cases, decreased in 4, and disappeared in 3. Postoperatively, all 7 patients with a decreased or absent CCEP response after lesion removal experienced deterioration in speech function. In contrast, in 5 cases with an unchanged intraoperative CCEP response, speaking abilities after surgery were preserved at the preoperative level, except in one patient who experienced not dysphasia, but dysarthria due to pyramidal tract injury. This difference was statistically significant (p < 0.01). The time required to recover speech function was also significantly associated with the type of intraoperative change in CCEP recordings (p < 0.01) and was, on average, 1.8 ± 1.0, 5.5 ± 1.0, and 11.0 ± 3.6 months, respectively, if the response was unchanged, was decreased, or had disappeared. CONCLUSIONS: Monitoring CCEP is feasible during the resection of brain tumors affecting language-related cerebral structures. In the intraoperative evaluation of speech function, it can be a helpful adjunct or can be used in its direct assessment with cortical and subcortical mapping during awake craniotomy. It can also be used to predict the prognosis of language disorders after surgery and decide on the optimal resection of a neoplasm.

Differential reorganization of three syntax-related networks induced by a left frontal glioma.

The opercular/triangular parts of the left inferior frontal gyrus and the left lateral premotor cortex are critical in syntactic processing. We have recently indicated that a glioma in one of these regions is sufficient to cause agrammatic comprehension. In the present study, we aimed to show how normally existing syntax-related networks are functionally reorganized by a lesion. Twenty-one patients with a left frontal glioma preoperatively performed a picture-sentence matching task, and underwent functional magnetic resonance imaging scans in an event-related design. We established two qualitatively different types of agrammatic comprehension, depending on glioma location. Patients with a glioma in the left lateral premotor cortex had a more profound deficit in the comprehension of scrambled sentences than that of active and passive sentences. In contrast, patients with a glioma in the opercular/triangular parts of the left inferior frontal gyrus had a more profound deficit in the comprehension of passive and scrambled sentences than that of active sentences. Moreover, we found dramatic changes in the activation patterns in these two patient groups, which accompanied abnormal overactivity and/or underactivity in the syntax-related regions. Furthermore, by examining functional connectivity in the normal brain, we identified three syntax-related networks among those regions, and anatomically visualized connections within individual networks by using diffusion tensor imaging. The first network consists of the opercular/triangular parts of the left inferior frontal gyrus, left intraparietal sulcus, right frontal regions, presupplementary motor area, and right temporal regions. These regions were overactivated in the patients with a glioma in the left lateral premotor cortex only for correct responses, indicating a cognitive change. The second network consists of the left lateral premotor cortex, left angular gyrus, lingual gyrus, and cerebellar nuclei. These regions were overactivated in the patients with a glioma in the opercular/triangular parts of the left inferior frontal gyrus for both correct and incorrect responses, indicating a neuronal change. The third network consists of the left ventral frontal and posterior temporal regions. These regions were underactivated in the patients with a glioma in the opercular/triangular parts of the left inferior frontal gyrus, indicating another neuronal change. These results demonstrate that agrammatic comprehension is associated with the global reorganization of functionally distinct networks, which indeed reflects a differential change in the relative contribution of these three networks to normal syntax-related functions.

Agrammatic comprehension caused by a glioma in the left frontal cortex.

It has been known that lesions in the left inferior frontal gyrus (L. IFG) do not always cause Broca's aphasia, casting doubt upon the specificity of this region. We have previously devised a picture-sentence matching task for a functional magnetic resonance imaging (fMRI) study, and observed that both pars triangularis (L. F3t) of L. IFG (extending to pars opercularis (L. F3op)) and the left lateral premotor cortex (L. LPMC) are selectively involved in syntactic processing. The present study with lesion-symptoms mapping was conducted to examine whether the function of these regions is indeed critical for syntactic comprehension. Using the same picture-sentence matching task, we examined 21 patients with a glioma in the left frontal cortex but with no apparent disability in verbal/written communication or intelligence quotient. This task included three main conditions of sentence types: canonical/subject-initial active sentences, non-canonical/subject-initial passive sentences, and non-canonical/object-initial scrambled sentences. The patients preoperatively underwent a high-resolution 3D-MRI, and voxel-based lesion-symptom mapping was employed for the error rates data. We found that the patients with a lesion in L. F3op/F3t or L. LPMC showed differential patterns of condition-selective deficits in the comprehension of sentences. More specifically, the L. F3op/F3t-damaged patients had more profound deficits in the comprehension of non-canonical sentences, whereas the L. LPMC-damaged patients had more profound deficits in the comprehension of object-initial scrambled sentences. These results establish that a lesion in L. F3op/F3t or L. LPMC is sufficient to cause agrammatic comprehension.