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.

Merge-Generability as the Key Concept of Human Language: Evidence From Neuroscience.

Ever since the inception of generative linguistics, various dependency patterns have been widely discussed in the literature, particularly as they pertain to the hierarchy based on "weak generation" - the so-called Chomsky Hierarchy. However, humans can make any possible dependency patterns by using artificial means on a sequence of symbols (e.g., computer programing). The differences between sentences in human language and general symbol sequences have been routinely observed, but the question as to why such differences exist has barely been raised. Here, we address this problem and propose a theoretical explanation in terms of a new concept of "Merge-generability," that is, whether the structural basis for a given dependency is provided by the fundamental operation Merge. In our functional magnetic resonance imaging (fMRI) study, we tested the judgments of noun phrase (NP)-predicate (Pred) pairings in sentences of Japanese, an SOV language that allows natural, unbounded nesting configurations. We further introduced two pseudo-adverbs, which artificially force dependencies that do not conform to structures generated by Merge, i.e., non-Merge-generable; these adverbs enable us to manipulate Merge-generability (Natural or Artificial). By employing this novel paradigm, we obtained the following results. Firstly, the behavioral data clearly showed that an NP-Pred matching task became more demanding under the Artificial conditions than under the Natural conditions, reflecting cognitive loads that could be covaried with the increased number of words. Secondly, localized activation in the left frontal cortex, as well as in the left middle temporal gyrus and angular gyrus, was observed for the [Natural - Artificial] contrast, indicating specialization of these left regions in syntactic processing. Any activation due to task difficulty was completely excluded from activations in these regions, because the Natural conditions were always easier than the Artificial ones. And finally, the [Artificial - Natural] contrast resulted in the dorsal portion of the left frontal cortex, together with wide-spread regions required for general cognitive demands. These results indicate that Merge-generable sentences are processed in these specific regions in contrast to non-Merge-generable sentences, demonstrating that Merge is indeed a fundamental operation, which comes into play especially under the Natural conditions.

Activation changes of the left inferior frontal gyrus for the factors of construction and scrambling in a sentence.

Our previous functional magnetic resonance imaging (fMRI) studies have indicated that the left dorsal inferior frontal gyrus (L. dF3op/F3t) and left lateral premotor cortex (L. LPMC) are crucial regions for syntactic processing among the syntax-related networks. In the present study, we further examined how activations in these regions were modified by the factors of construction and scrambling (object-initial type). Using various sentence types, we clarified three major points. First, we found that the main effects of construction and scrambling consistently activated the L. dF3op/F3t and L. LPMC. Secondly, the main effects of scrambling clearly localized activation in the L. dF3op/F3t and L. LPMC, indicating the more narrowed down processing of syntax. Thirdly, step-wise percent signal changes were observed in the L. dF3op/F3t, demonstrating synergistic effects of construction and scrambling. These results demonstrate the abstract and intensive nature of syntactic processing carried out by these regions, i.e., the grammar center.