Publications by authors named "Kuniyoshi L Sakai"

54 Publications

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

Cereb Cortex Commun 2020 1;1(1):tgaa061. Epub 2020 Sep 1.

Department of Basic Science, Graduate School of Arts and Sciences, The University of Tokyo, Tokyo 153-8902, Japan.

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 -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.
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http://dx.doi.org/10.1093/texcom/tgaa061DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8152871PMC
September 2020

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

Cereb Cortex Commun 2020 27;1(1):tgaa027. Epub 2020 Jun 27.

Department of Basic Science, Graduate School of Arts and Sciences, The University of Tokyo, Tokyo, 153-8902, Japan.

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 hemisphere were mainly characterized by a decrease in CT and mild concomitant decrease in FD, whereas those in the peripheral regions of the glioma ( 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.
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http://dx.doi.org/10.1093/texcom/tgaa027DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8152868PMC
June 2020

Modality-Dependent Brain Activation Changes Induced by Acquiring a Second Language Abroad.

Front Behav Neurosci 2021 26;15:631957. Epub 2021 Mar 26.

Department of Basic Science, Graduate School of Arts and Sciences, The University of Tokyo, Tokyo, Japan.

The dynamic nature of cortical activation changes during language acquisition, including second-language learning, has not been fully elucidated. In this study, we administered two sets of reading and listening tests (Pre and Post) to participants who had begun to learn Japanese abroad. The two sets were separated by an interval of about 2 months of Japanese language training. We compared the results of longitudinal functional MRI experiments between the two time-points and obtained the following major findings. First, the left-dominant language areas, as well as bilateral visual and auditory areas, were activated, demonstrating the synergistic effects of multiple modalities. There was also significant activation in the bilateral hippocampi, indicating the expected involvement of memory-related processes. Second, consistent with the behavioral improvements from Pre to Post, the brain activations in the left inferior and middle frontal gyri during the listening tests, as well as in the visual areas (the bilateral inferior and superior parietal lobules, and left inferior and middle occipital gyri) during the reading tests, while activations in the right superior and middle temporal gyri during the listening tests. These modality-dependent activation changes could not be explained by domain-general cognitive factors, such as habituation or familiarization, because we used completely different test sets for Pre and Post. Third, the posterior hippocampus showed a main effect of the hemisphere, whereas the anterior hippocampus showed a significant main effect of the event (i.e., specific to first listening events), reflecting initial encoding of auditory information alone. In summary, activation changes from Pre to Post indicate functional changes in modality-dependent networks over a short period of staying abroad, which would enable effective acquisition of a second language.
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http://dx.doi.org/10.3389/fnbeh.2021.631957DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8032875PMC
March 2021

Paper Notebooks vs. Mobile Devices: Brain Activation Differences During Memory Retrieval.

Front Behav Neurosci 2021 19;15:634158. Epub 2021 Mar 19.

Department of Basic Science, Graduate School of Arts and Sciences, The University of Tokyo, Tokyo, Japan.

It remains to be determined how different inputs for memory-encoding, such as the use of paper notebooks or mobile devices, affect retrieval processes. We compared three groups of participants who read dialogues on personal schedules and wrote down the scheduled appointments on a calendar using a paper notebook (Note), an electronic tablet (Tablet), or a smartphone (Phone). After the retention period for an hour including an interference task, we tested recognition memory of those appointments with visually presented questions in a retrieval task, while scanned with functional magnetic resonance imaging. We obtained three major results. First, the duration of writing down schedules was significantly shorter for the Note group than the Tablet and Phone groups, and accuracy was much higher for the Note group in easier (i.e., more straightforward) questions. Because the input methods were equated as much as possible between the Note and Tablet groups, these results indicate that the cognitive processes for the Note group were deeper and more solid. Second, brain activations for all participants during the retrieval phase were localized in the bilateral hippocampus, precuneus, visual cortices, and language-related frontal regions, confirming the involvement of verbalized memory retrieval processes for appointments. Third, activations in these regions were significantly higher for the Note group than those for the Tablet and Phone groups. These enhanced activations for the Note group could not be explained by general cognitive loads or task difficulty, because overall task performances were similar among the groups. The significant superiority in both accuracy and activations for the Note group suggested that the use of a paper notebook promoted the acquisition of rich encoding information and/or spatial information of real papers and that this information could be utilized as effective retrieval clues, leading to higher activations in these specific regions.
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http://dx.doi.org/10.3389/fnbeh.2021.634158DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8017158PMC
March 2021

Enhanced activations in syntax-related regions for multilinguals while acquiring a new language.

Sci Rep 2021 Mar 31;11(1):7296. Epub 2021 Mar 31.

Department of Basic Science, Graduate School of Arts and Sciences, The University of Tokyo, 3-8-1 Komaba, Meguro-ku, Tokyo, 153-8902, Japan.

The neuroscientific foundation of multilingualism, a unique cognitive capacity, necessitates further elucidation. We conducted an fMRI experiment to evaluate the acquisition of syntactic features in a new language (Kazakh) for multilinguals and bilinguals. Results showed that the multilinguals who were more proficient in their second/third languages needed fewer task trials to acquire Kazakh phonology. Regarding group differences, the reduction in response times during the initial exposure to Kazakh were significantly larger for the multilinguals than the bilinguals. For the multilinguals, activations in the bilateral frontal/temporal regions were maintained at a higher level than the initial level during subsequent new grammar conditions. For the bilinguals, activations in the basal ganglia/thalamus and cerebellum decreased to the initial level each time. Direct group comparisons showed significantly enhanced activations for the multilinguals in the left ventral inferior frontal gyrus. These results indicate that both syntax-related and domain-general brain networks were more enhanced for the multilinguals. We also unexpectedly observed significant activations in the visual areas for the multilinguals, implying the use of visual representation even when listening to speech sounds alone. Because the multilinguals were able to successfully utilize acquired knowledge in an accumulated manner, the results support the cumulative-enhancement model of language acquisition.
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http://dx.doi.org/10.1038/s41598-021-86710-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8012711PMC
March 2021

[Multilingualism and the Development of the Brain].

Brain Nerve 2021 Mar;73(3):203-210

Department of Basic Science, Graduate School of Arts and Sciences, The University of Tokyo.

Multilingualism is merely a parametric variation in the faculty of natural language, and it is possible to simultaneously acquire multiple languages, including dialects, at any age. While acquisition of a native language, which occurs in synchrony with development of the brain, is a multiple-step process, second language acquisition is continuous. Here, we introduce the Cumulative-Enhancement model, which states that acquisition of one additional language is beneficial for the subsequent acquisition of another. We further discuss how syntax-related networks, including multiple language areas in the brain, become functional during the course of language acquisition.
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http://dx.doi.org/10.11477/mf.1416201741DOI Listing
March 2021

[Brain Activations Reflecting Mental States Induced by the Context of Cartoons].

Brain Nerve 2021 Jan;73(1):79-87

Department of Basic Science, Graduate School of Arts and Sciences, The University of Tokyo.

Although context can be presumed to exert effects on both language and visual information processing, the relevant brain regions have not been elucidated. In the present study, we used silent manga to focus on mental states induced by visual stimuli alone. When participants read manga on a double-page spread with preserved context, significant activation was observed in the bilateral visual cortex and cerebellum. Moreover, the activated region corresponded to lesions associated with hemispatial neglect, when this condition was directly compared with a single-page presentation that impaired context. These results indicate that higher-order visual information processing is enhanced by context.
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http://dx.doi.org/10.11477/mf.1416201713DOI Listing
January 2021

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

Front Psychol 2019 29;10:2673. Epub 2019 Nov 29.

Department of Basic Science, Graduate School of Arts and Sciences, The University of Tokyo, Tokyo, Japan.

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 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 , unbounded nesting configurations. We further introduced two pseudo-adverbs, which force dependencies that do conform to structures generated by Merge, i.e., non-Merge-generable; these adverbs enable us to manipulate Merge-generability ( or ). 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.
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http://dx.doi.org/10.3389/fpsyg.2019.02673DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6895067PMC
November 2019

[The Last Lecture of Professor Masao Ito: The Cerebellum and Cerebrum].

Brain Nerve 2019 Dec;71(12):1391-1396

Department of Basic Science, Graduate School of Arts and Sciences, The University of Tokyo.

Comment Professor Masao Ito's last lecture, delivered at the University of Tokyo Faculty of Medicine on March 7, 1989, is reproduced here in an abridged form. Its original title was "the Cerebellum and Cerebrum," and this lecture was a real masterpiece, full of insights and suggestions on brain functions, together with humorous phrases here and there. When I tried to reproduce this lecture by using all figures at that time, just one week after Professor Ito passed away, I was struck by his foresight even after thirty years. I deeply appreciate his family's permission for the reproduction.
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http://dx.doi.org/10.11477/mf.1416201459DOI Listing
December 2019

[Lateralization of the Frontal Association Cortex: Syntax-related Networks].

Brain Nerve 2018 Oct;70(10):1075-1085

Department of Neurology, Showa University Fujigaoka Hospital.

The left inferior frontal gyrus, a part of the left frontal association cortex, is known to be involved in syntactic processing. Recently, we identified three syntax-related networks, which included each of the three regions of the left frontal association cortex. Moreover, patients with agrammatic comprehension caused by damage to the left association cortex showed changes in functional connectivity in the entire syntax-related network. These findings suggest that the left frontal association cortex is at the core of syntax-related networks.
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http://dx.doi.org/10.11477/mf.1416201139DOI Listing
October 2018

[The Brain, the Source of Multilingualism].

Brain Nerve 2018 Jun;70(6):633-638

Department of Basic Science, Graduate School of Arts and Sciences, The University of Tokyo.

Multiple languages can be used at command, if those language abilities were acquired in childhood. In this article, we report the possibility that such abilities are retained throughout adulthood for linguistic savants. We focus on Emil Krebs, a speaker of dozens of languages, and argue about the vast capacity of the multilingual brain. Moreover, we introduce the asymmetry of the grammar center and brain activation changes due to linguistic proficiency, both of which are findings from research on the second language acquisition capability of the brain. It is plausible that research on multilingualism will shed light on the mystery of human creativity in fine arts.
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http://dx.doi.org/10.11477/mf.1416201055DOI Listing
June 2018

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

Proc Jpn Acad Ser B Phys Biol Sci 2017 ;93(7):511-522

Department of Basic Science, Graduate School of Arts and Sciences, The University of Tokyo.

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.
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http://dx.doi.org/10.2183/pjab.93.031DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5713179PMC
March 2018

Differential Signatures of Second Language Syntactic Performance and Age on the Structural Properties of the Left Dorsal Pathway.

Front Psychol 2017 23;8:829. Epub 2017 May 23.

Department of Basic Science, Graduate School of Arts and Sciences, The University of TokyoTokyo, Japan.

In adult second language (L2) acquisition, individual differences are considerably large even among people with similar experiences. The neural mechanisms underlying this variability would include structural plasticity of language-related pathways. To elucidate such neuroplasticity, we focused on the transitional period of adolescence, which is associated with certain plasticity toward maturation following the sensitive period of language acquisition (≤12 years old). The adolescent brain would thus be influenced by age-dependent factors, as well as performances in L2. Here, we examined individual differences in L2 performances controlling the duration of experience to reveal the differential signatures of performances and age on the plasticity of structural properties in major language-related pathways. We recruited Japanese students at two ages, i.e., junior (age: 13-14) and senior (age: 16-17) high-school students, all of whom started to expose to English at age 12 or 13. We divided them into subgroups, so that either L2 performance [Junior (High)/Senior (Low)] or age [Senior (Low)/Senior (High)] was matched in group comparisons; the duration of L2 experience was also controlled between the Senior (Low) and Senior (High) groups. We then examined the thickness and fractional anisotropy (FA) of the dorsal and ventral pathways, i.e., the arcuate fasciculus (Arcuate) and inferior fronto-occipital fasciculus (IFOF), respectively, using semi-automatic methods for selecting regions without branches. Regarding FA in the left Arcuate, the Senior (High) group showed significantly higher FA than the other two groups, indicating performance-related group differences. Further, FA in the left Arcuate was selectively correlated with the accuracy of a syntactic task. Regarding the thickness of the left Arcuate, the Senior (High) and Senior (Low) groups showed significantly larger thickness than the Junior (High) group, indicating age-related group differences. These differential performance-related and age-related signatures were evident on the left Arcuate alone, in contrast to the right Arcuate that showed only mild differences in thickness, and to the bilateral IFOF that lacked either signature. Our results suggest that the left dorsal pathway continued to develop to adolescence, and that performance differences in a syntactic task can be predicted by its FA, independent of age and the duration of experience.
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http://dx.doi.org/10.3389/fpsyg.2017.00829DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5440582PMC
May 2017

Dissociating Effects of Scrambling and Topicalization within the Left Frontal and Temporal Language Areas: An fMRI Study in Kaqchikel Maya.

Front Psychol 2017 9;8:748. Epub 2017 May 9.

Department of Basic Science, Graduate School of Arts and Sciences, The University of TokyoTokyo, Japan.

Some natural languages grammatically allow different types of changing word orders, such as object scrambling and topicalization. Scrambling and topicalization are more related to syntax and semantics/phonology, respectively. Here we hypothesized that scrambling should activate the left frontal regions, while topicalization would affect the bilateral temporal regions. To examine such distinct effects in our functional magnetic resonance imaging study, we targeted the Kaqchikel Maya language, a Mayan language spoken in Guatemala. In Kaqchikel, the syntactically canonical word order is verb-object-subject (VOS), but at least three non-canonical word orders (i.e., SVO, VSO, and OVS) are also grammatically allowed. We used a sentence-picture matching task, in which the participants listened to a short Kaqchikel sentence and judged whether a picture matched the meaning of the sentence. The advantage of applying this experimental paradigm to an understudied language such as Kaqchikel is that it will allow us to validate the universality of linguistic computation in the brain. We found that the conditions with scrambled sentences [+scrambling] elicited significant activation in the left inferior frontal gyrus and lateral premotor cortex, both of which have been proposed as grammar centers, indicating the effects of syntactic loads. In contrast, the conditions without topicalization [-topicalization] resulted in significant activation in bilateral Heschl's gyrus and superior temporal gyrus, demonstrating that the syntactic and phonological processes were clearly dissociated within the language areas. Moreover, the pre-supplementary motor area and left superior/middle temporal gyri were activated under relatively demanding conditions, suggesting their supportive roles in syntactic or semantic processing. To exclude any semantic/phonological effects of the object-subject word orders, we performed direct comparisons while making the factor of topicalization constant, and observed localized activations in the left inferior frontal gyrus and lateral premotor cortex. These results establish that the types of scrambling and topicalization have different impacts on the specified language areas. These findings further indicate that the functional roles of these left frontal and temporal regions involve aspects themselves, namely syntax versus semantics/phonology, rather than output/input aspects of speech processing.
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http://dx.doi.org/10.3389/fpsyg.2017.00748DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5422526PMC
May 2017

[Syntactic Processing in Broca's Area: Brodmann Areas 44 and 45].

Brain Nerve 2017 Apr;69(4):479-487

Department of Physics, Graduate School of Science, The University of Tokyo.

Brodmann areas 44 and 45 are known as Broca's area; however, their true functional roles are still unknown. Recent developments in neuroimaging techniques revealed the structures and functions of Broca's area in detail. More specifically regarding language functions, sufficient evidence has been accumulated that this region subserves the center of syntactic processing, not necessarily motor functions. Here, we review a role of Broca's area as the grammar center, including other roles in nonlinguistic functions.
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http://dx.doi.org/10.11477/mf.1416200767DOI Listing
April 2017

[Language Functions in the Frontal Association Area: Brain Mechanisms That Create Language].

Brain Nerve 2016 Nov;68(11):1283-1290

Department of Basic Science, Graduate School of Arts and Sciences, The University of Tokyo.

Broca's area is known to be critically involved in language processing for more than 150 years. Recent neuroimaging techniques, including functional magnetic resonance imaging (fMRI) and diffusion MRI, enabled the subdivision of Broca's area based on both functional and anatomical aspects. Networks among the frontal association areas, especially the left inferior frontal gyrus (IFG), and other cortical regions in the temporal/parietal association areas, are also important for language-related information processing. Here, we review how neuroimaging studies, combined with research paradigms based on theoretical linguistics, have contributed to clarifying the critical roles of the left IFG in syntactic processing and those of language-related networks, including cortical and cerebellar regions.
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http://dx.doi.org/10.11477/mf.1416200592DOI Listing
November 2016

The Dorsal Rather than Ventral Pathway Better Reflects Individual Syntactic Abilities in Second Language.

Front Hum Neurosci 2016 14;10:295. Epub 2016 Jun 14.

Department of Basic Science, Graduate School of Arts and Sciences, The University of TokyoTokyo, Japan; Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology AgencyTokyo, Japan.

The left inferior frontal gyrus (IFG) has been reported to be critically involved in syntactic processing, not only in first language (L1), but in second language (L2). Indeed, the leftward lateralization of the IFG has been shown to be correlated with the performance of a syntactic task in L2. Given that posterior language-related regions are systematically connected with the left IFG, the next question is which of the dorsal and ventral pathways is more critical to the individual syntactic abilities in L2. Here we used diffusion magnetic resonance imaging (MRI) and tractography with newly developed semi-automatic methods of defining seeds and selecting regions of interest (ROIs). We calculated mean thickness and fractional anisotropy (FA) in each ROI for the arcuate fasciculus (Arcuate) of the dorsal pathway, as well as for the inferior fronto-occipital fasciculus (IFOF) of the ventral pathway. In Experiment I, we performed partial correlation analyses between FA and the accuracy of the syntactic task, removing the effects of the accuracy of a spelling task, gender, and handedness. Among the two pathways in each hemisphere, only FA of the left Arcuate was significantly correlated with individual accuracy of the syntactic task. In Experiment II, we recruited monozygotic twins and examined to what extent their L2 abilities and their structural properties were similar. Within twin pairs, the highest significant correlation was observed for reaction times of the spelling task, while the correlation for the accuracy of the syntactic task was marginal; these two correlation coefficients were significantly different. Moreover, the thickness of the left Arcuate was highly correlated within pairs, while its FA, as well as the thickness/FA in the ventral pathways, was not significantly correlated. The correlation coefficient for the thickness of the left Arcuate was significantly larger than that of the left IFOF. These results suggest that the thickness of the left Arcuate is more associated with the shared genetic/environmental factors, whereas both of mutually correlated FA in the left Arcuate and individual syntactic abilities in L2 may be less prone to these shared factors.
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http://dx.doi.org/10.3389/fnhum.2016.00295DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4906050PMC
July 2016

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

J Neurosurg 2016 10 22;125(4):803-811. Epub 2016 Jan 22.

Departments of 1 Neurosurgery and.

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.
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http://dx.doi.org/10.3171/2015.8.JNS151204DOI Listing
October 2016

[Visualization of Gray Matter Myelin and Fiber Bundles Critical for Relative Pitch: A Role of the Left Posterior Long Insular Cortex].

Brain Nerve 2015 Sep;67(9):1147-55

Department of Basic Science, Graduate School of Arts and Sciences, The University of Tokyo.

Relative pitch is the ability to identify a tone pitch based on external or internal pitches. Here we used magnetic resonance imaging (MRI) to determine which cortical region is responsible for relative pitch. Forty-eight participants were asked to listen to 24 piano tones, and then write down the names of the tones (except reference tones of a(1)=440 Hz, which were intermittently presented three times). We classified the participants into three groups based on their task scores: Group A (n=12, full points), Group B (n=22, 6-20 points), and Group C (n=14, 0-5 points). We focused on the myelin of the gray matter, which can be visualized by the ratio of MR signals from a pair of T(1)- and T(2)-weighted images. We found significantly increased ratios in the left posterior long insular cortex for Group A. We also observed more consistent pathways in the anterior region of the left middle longitudinal fasciculus for Group A compared to Group C, which passed through the left superior temporal gyrus. Because these regions are involved in the processing of speech sounds, the present results suggest that the ability to identify musical pitches is associated with universal linguistic abilities.
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http://dx.doi.org/10.11477/mf.1416200274DOI Listing
September 2015

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

Springerplus 2015 4;4:317. Epub 2015 Jul 4.

Department of Basic Science, Graduate School of Arts and Sciences, The University of Tokyo, 3-8-1 Komaba, Meguro-ku, Tokyo, 153-8902 Japan ; CREST, Japan Science and Technology Agency, 7 Gobancho, Chiyoda-ku, Tokyo, 102-0076 Japan.

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.
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http://dx.doi.org/10.1186/s40064-015-1104-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4491091PMC
July 2015

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

Brain Nerve 2015 Mar;67(3):303-10

Division of Neurology, Department of Internal Medicine, Showa University Northern Yokohama Hospital.

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.
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http://dx.doi.org/10.11477/mf.1416200136DOI Listing
March 2015

Language and cognition.

Front Behav Neurosci 2014 16;8:436. Epub 2014 Dec 16.

Department of Basic Science, Graduate School of Arts and Sciences, The University of Tokyo Tokyo, Japan.

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http://dx.doi.org/10.3389/fnbeh.2014.00436DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4267264PMC
January 2015

Subliminal enhancement of predictive effects during syntactic processing in the left inferior frontal gyrus: an MEG study.

Front Syst Neurosci 2014 3;8:217. Epub 2014 Nov 3.

Department of Basic Science, Graduate School of Arts and Sciences, The University of Tokyo Meguro-ku, Japan ; CREST, Japan Science and Technology Agency Chiyoda-ku, Japan.

Predictive syntactic processing plays an essential role in language comprehension. In our previous study using Japanese object-verb (OV) sentences, we showed that the left inferior frontal gyrus (IFG) responses to a verb increased at 120-140 ms after the verb onset, indicating predictive effects caused by a preceding object. To further elucidate the automaticity of the predictive effects in the present magnetoencephalography study, we examined whether a subliminally presented verb ("subliminal verb") enhanced the predictive effects on the sentence-final verb ("target verb") unconsciously, i.e., without awareness. By presenting a subliminal verb after the object, enhanced predictive effects on the target verb would be detected in the OV sentences when the transitivity of the target verb matched with that of the subliminal verb ("congruent condition"), because the subliminal verb just after the object could determine the grammaticality of the sentence. For the OV sentences under the congruent condition, we observed significantly increased left IFG responses at 140-160 ms after the target verb onset. In contrast, responses in the precuneus and midcingulate cortex (MCC) were significantly reduced for the OV sentences under the congruent condition at 110-140 and 280-300 ms, respectively. By using partial Granger causality analyses for the OV sentences under the congruent condition, we revealed a bidirectional interaction between the left IFG and MCC at 60-160 ms, as well as a significant influence from the MCC to the precuneus. These results indicate that a top-down influence from the left IFG to the MCC, and then to the precuneus, is critical in syntactic decisions, whereas the MCC shares its task-set information with the left IFG to achieve automatic and predictive processes of syntax.
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http://dx.doi.org/10.3389/fnsys.2014.00217DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4217366PMC
November 2014

Neural mechanisms underlying the computation of hierarchical tree structures in mathematics.

PLoS One 2014 7;9(11):e111439. Epub 2014 Nov 7.

Department of Basic Science, Graduate School of Arts and Sciences, The University of Tokyo, Komaba, Meguro-ku, Tokyo, Japan; CREST, Japan Science and Technology Agency, Goban-cho, Chiyoda-ku, Tokyo, Japan.

Whether mathematical and linguistic processes share the same neural mechanisms has been a matter of controversy. By examining various sentence structures, we recently demonstrated that activations in the left inferior frontal gyrus (L. IFG) and left supramarginal gyrus (L. SMG) were modulated by the Degree of Merger (DoM), a measure for the complexity of tree structures. In the present study, we hypothesize that the DoM is also critical in mathematical calculations, and clarify whether the DoM in the hierarchical tree structures modulates activations in these regions. We tested an arithmetic task that involved linear and quadratic sequences with recursive computation. Using functional magnetic resonance imaging, we found significant activation in the L. IFG, L. SMG, bilateral intraparietal sulcus (IPS), and precuneus selectively among the tested conditions. We also confirmed that activations in the L. IFG and L. SMG were free from memory-related factors, and that activations in the bilateral IPS and precuneus were independent from other possible factors. Moreover, by fitting parametric models of eight factors, we found that the model of DoM in the hierarchical tree structures was the best to explain the modulation of activations in these five regions. Using dynamic causal modeling, we showed that the model with a modulatory effect for the connection from the L. IPS to the L. IFG, and with driving inputs into the L. IFG, was highly probable. The intrinsic, i.e., task-independent, connection from the L. IFG to the L. IPS, as well as that from the L. IPS to the R. IPS, would provide a feedforward signal, together with negative feedback connections. We indicate that mathematics and language share the network of the L. IFG and L. IPS/SMG for the computation of hierarchical tree structures, and that mathematics recruits the additional network of the L. IPS and R. IPS.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0111439PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4224410PMC
July 2015

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

J Neurosurg 2014 Oct 30;121(4):827-38. Epub 2014 May 30.

Department of Neurosurgery;

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.
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http://dx.doi.org/10.3171/2014.4.JNS131195DOI Listing
October 2014

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

Brain 2014 Apr 11;137(Pt 4):1193-212. Epub 2014 Feb 11.

1 Department of Basic Science, Graduate School of Arts and Sciences, The University of Tokyo, Tokyo 153-8902, Japan.

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.
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http://dx.doi.org/10.1093/brain/awu013DOI Listing
April 2014

Computational principles of syntax in the regions specialized for language: integrating theoretical linguistics and functional neuroimaging.

Front Behav Neurosci 2013 18;7:204. Epub 2013 Dec 18.

Department of Life Sciences, Graduate School of Arts and Sciences, The University of Tokyo Tokyo, Japan ; CREST, Japan Science and Technology Agency Tokyo, Japan ; Department of Basic Science, Graduate School of Arts and Sciences, The University of Tokyo Tokyo, Japan.

The nature of computational principles of syntax remains to be elucidated. One promising approach to this problem would be to construct formal and abstract linguistic models that parametrically predict the activation modulations in the regions specialized for linguistic processes. In this article, we review recent advances in theoretical linguistics and functional neuroimaging in the following respects. First, we introduce the two fundamental linguistic operations: Merge (which combines two words or phrases to form a larger structure) and Search (which searches and establishes a syntactic relation of two words or phrases). We also illustrate certain universal properties of human language, and present hypotheses regarding how sentence structures are processed in the brain. Hypothesis I is that the Degree of Merger (DoM), i.e., the maximum depth of merged subtrees within a given domain, is a key computational concept to properly measure the complexity of tree structures. Hypothesis II is that the basic frame of the syntactic structure of a given linguistic expression is determined essentially by functional elements, which trigger Merge and Search. We then present our recent functional magnetic resonance imaging experiment, demonstrating that the DoM is indeed a key syntactic factor that accounts for syntax-selective activations in the left inferior frontal gyrus and supramarginal gyrus. Hypothesis III is that the DoM domain changes dynamically in accordance with iterative Merge applications, the Search distances, and/or task requirements. We confirm that the DoM accounts for activations in various sentence types. Hypothesis III successfully explains activation differences between object- and subject-relative clauses, as well as activations during explicit syntactic judgment tasks. A future research on the computational principles of syntax will further deepen our understanding of uniquely human mental faculties.
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http://dx.doi.org/10.3389/fnbeh.2013.00204DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3866525PMC
January 2014

Functional and anatomical correlates of word-, sentence-, and discourse-level integration in sign language.

Front Hum Neurosci 2013 22;7:681. Epub 2013 Oct 22.

Department of Basic Science, Graduate School of Arts and Sciences, The University of Tokyo Tokyo, Japan ; Japan Society for the Promotion of Science Tokyo, Japan.

In both vocal and sign languages, we can distinguish word-, sentence-, and discourse-level integration in terms of hierarchical processes, which integrate various elements into another higher level of constructs. In the present study, we used magnetic resonance imaging and voxel-based morphometry (VBM) to test three language tasks in Japanese Sign Language (JSL): word-level (Word), sentence-level (Sent), and discourse-level (Disc) decision tasks. We analyzed cortical activity and gray matter (GM) volumes of Deaf signers, and clarified three major points. First, we found that the activated regions in the frontal language areas gradually expanded in the dorso-ventral axis, corresponding to a difference in linguistic units for the three tasks. Moreover, the activations in each region of the frontal language areas were incrementally modulated with the level of linguistic integration. These dual mechanisms of the frontal language areas may reflect a basic organization principle of hierarchically integrating linguistic information. Secondly, activations in the lateral premotor cortex and inferior frontal gyrus were left-lateralized. Direct comparisons among the language tasks exhibited more focal activation in these regions, suggesting their functional localization. Thirdly, we found significantly positive correlations between individual task performances and GM volumes in localized regions, even when the ages of acquisition (AOAs) of JSL and Japanese were factored out. More specifically, correlations with the performances of the Word and Sent tasks were found in the left precentral/postcentral gyrus and insula, respectively, while correlations with those of the Disc task were found in the left ventral inferior frontal gyrus and precuneus. The unification of functional and anatomical studies would thus be fruitful for understanding human language systems from the aspects of both universality and individuality.
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http://dx.doi.org/10.3389/fnhum.2013.00681DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3804906PMC
October 2013

Syntactic computation in the human brain: the degree of merger as a key factor.

PLoS One 2013 20;8(2):e56230. Epub 2013 Feb 20.

Department of Life Sciences, Graduate School of Arts and Sciences, The University of Tokyo, Komaba, Meguro-ku, Tokyo, Japan.

Our goal of this study is to characterize the functions of language areas in most precise terms. Previous neuroimaging studies have reported that more complex sentences elicit larger activations in the left inferior frontal gyrus (L. F3op/F3t), although the most critical factor still remains to be identified. We hypothesize that pseudowords with grammatical particles and morphosyntactic information alone impose a construction of syntactic structures, just like normal sentences, and that "the Degree of Merger" (DoM) in recursively merged sentences parametrically modulates neural activations. Using jabberwocky sentences with distinct constructions, we fitted various parametric models of syntactic, other linguistic, and nonlinguistic factors to activations measured with functional magnetic resonance imaging. We demonstrated that the models of DoM and "DoM+number of Search (searching syntactic features)" were the best to explain activations in the L. F3op/F3t and supramarginal gyrus (L. SMG), respectively. We further introduced letter strings, which had neither lexical associations nor grammatical particles, but retained both matching orders and symbol orders of sentences. By directly contrasting jabberwocky sentences with letter strings, localized activations in L. F3op/F3t and L. SMG were indeed independent of matching orders and symbol orders. Moreover, by using dynamic causal modeling, we found that the model with a inhibitory modulatory effect for the bottom-up connectivity from L. SMG to L. F3op/F3t was the best one. For this best model, the top-down connection from L. F3op/F3t to L. SMG was significantly positive. By using diffusion-tensor imaging, we confirmed that the left dorsal pathway of the superior longitudinal and arcuate fasciculi consistently connected these regions. Lastly, we established that nonlinguistic order-related and error-related factors significantly activated the right (R.) lateral premotor cortex and R. F3op/F3t, respectively. These results indicate that the identified network of L. F3op/F3t and L. SMG subserves the calculation of DoM in recursively merged sentences.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0056230PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3577822PMC
August 2013

Left inferior frontal activations depending on the canonicity determined by the argument structures of ditransitive sentences: an MEG study.

PLoS One 2012 22;7(5):e37192. Epub 2012 May 22.

Department of Basic Science, Graduate School of Arts and Sciences, The University of Tokyo, Komaba, Meguro-ku, Tokyo, Japan.

To elucidate the relationships between syntactic and semantic processes, one interesting question is how syntactic structures are constructed by the argument structure of a verb, where each argument corresponds to a semantic role of each noun phrase (NP). Here we examined the effects of possessivity [sentences with or without a possessor] and canonicity [canonical or noncanonical word orders] using Japanese ditransitive sentences. During a syntactic decision task, the syntactic structure of each sentence would be constructed in an incremental manner based on the predicted argument structure of the ditransitive verb in a verb-final construction. Using magnetoencephalography, we found a significant canonicity effect on the current density in the left inferior frontal gyrus (IFG) at 530-550 ms after the verb onset. This effect was selective to canonical sentences, and significant even when the precedent NP was physically identical. We suggest that the predictive effects associated with syntactic processing became larger for canonical sentences, where the NPs and verb were merged with a minimum structural distance, leading to the left IFG activations. For monotransitive and intransitive verbs, in which structural computation of the sentences was simpler than that of ditransitive sentences, we observed a significant effect selective to noncanonical sentences in the temporoparietal regions during 480-670 ms. This effect probably reflects difficulty in semantic processing of noncanonical sentences. These results demonstrate that the left IFG plays a predictive role in syntactic processing, which depends on the canonicity determined by argument structures, whereas other temporoparietal regions would subserve more semantic aspects of sentence processing.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0037192PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3358340PMC
December 2012
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