Asymmetric projections of the arcuate fasciculus to the temporal cortex underlie lateralized language function in the human brain

The arcuate fasciculus (AF) in the human brain has asymmetric structural properties. However, the topographic organization of the asymmetric AF projections to the cortex and its relevance to cortical function remain unclear. Here we mapped the posterior projections of the human AF in the inferior parietal and lateral temporal cortices using surface-based structural connectivity analysis based on diffusion MRI and investigated their hemispheric differences. We then performed the cross-modal comparison with functional connectivity based on resting-state functional MRI (fMRI) and task-related cortical activation based on fMRI using a semantic classification task of single words. Structural connectivity analysis showed that the left AF connecting to Broca's area predominantly projected in the lateral temporal cortex extending from the posterior superior temporal gyrus to the mid part of the superior temporal sulcus and the middle temporal gyrus, whereas the right AF connecting to the right homolog of Broca's area predominantly projected to the inferior parietal cortex extending from the mid part of the supramarginal gyrus to the anterior part of the angular gyrus. The left-lateralized projection regions of the AF in the left temporal cortex had asymmetric functional connectivity with Broca's area, indicating structure-function concordance through the AF. During the language task, left-lateralized cortical activation was observed. Among them, the brain responses in the temporal cortex and Broca's area that were connected through the left-lateralized AF pathway were specifically correlated across subjects. These results suggest that the human left AF, which structurally and functionally connects the mid temporal cortex and Broca's area in asymmetrical fashion, coordinates the cortical activity in these remote cortices during a semantic decision task. The unique feature of the left AF is discussed in the context of the human capacity for language.National Institutes of Health (U.S.) (Grant R01NS069696)National Institutes of Health (U.S.) (Grant P41EB015896)National Institutes of Health (U.S.) (Grant S10ODRR031599)National Institutes of Health (U.S.) (Grant S10RR021110)National Science Foundation (U.S.) (Grant NFS-DMS-1042134)Uehara Memorial Foundation (Fellowship)Society of Nuclear Medicine and Molecular Imaging (Wagner-Torizuka Fellowship)United States. Dept. of Energy (Grant DE-SC0008430

ナンチセイ ナイソク ソクトウヨウ テンカン カンジャ ニ オケル ゼントウ ゼンヤ キノウ テイカ

京都大学0048新制・課程博士博士(医学)甲第12652号医博第3021号新制||医||934(附属図書館)UT51-2006-U357京都大学大学院医学研究科脳統御医科学系専攻(主査)教授 髙橋 良輔, 教授 河野 憲二, 教授 林 拓二学位規則第4条第1項該当Doctor of Medical ScienceKyoto UniversityDA

Task-dependent reorganization of functional connectivity networks during visual semantic decision making

INTRODUCTION: Functional MRI is widely used to study task-related changes in neuronal activity as well as resting-state functional connectivity. In this study, we explore task-related changes in functional connectivity networks using fMRI. Dynamic connectivity may represent a new measure of neural network robustness that would impact both clinical and research efforts. However, prior studies of task-related changes in functional connectivity have shown apparently conflicting results, leading to several competing hypotheses regarding the relationship between task-related and resting-state brain networks. METHODS: We used a graph theory-based network approach to compare functional connectivity in healthy subjects between the resting state and when performing a clinically used semantic decision task. We analyzed fMRI data from 21 healthy, right-handed subjects. RESULTS: While three nonoverlapping, highly intraconnected functional modules were observed in the resting state, an additional language-related module emerged during the semantic decision task. Both overall and within-module connectivity were greater in default mode network (DMN) and classical language areas during semantic decision making compared to rest, while between-module connectivity was diffusely greater at rest, revealing a more widely distributed pattern of functional connectivity at rest. CONCLUSIONS: The results of this study suggest that there are differences in network topology between resting and task states. Specifically, semantic decision making is associated with a reduction in distributed connectivity through hub areas of the DMN as well as an increase in connectivity within both default and language networks

The lack of expression of the peripheral benzodiazepine receptor characterises microglial response in anaplastic astrocytomas.

The peripheral benzodiazepine receptor (PBR) is a 18 kDa molecule mainly involved in cholesterol transport through the mitochondrial membrane. In microglia, PBR is expressed from the earliest stages of activation and appears to exert a pro-inflammatory function. This molecule is commonly up-regulated in inflammatory, degenerative, infective and ischaemic lesions of the central nervous system but it has never been reported in glioma-infiltrating microglia. We examined two anaplastic astrocytomas showing minimal contrast-enhancement and therefore little damage of the blood brain barrier to minimise the presence of blood borne macrophages within tumour tissue. The two lesions were studied in vivo using positron emission tomography (PET) with the specific PBR ligand [(11)C](R)-PK11195 and the corresponding tumour tissue was investigated with an anti-PBR antibody. Glioma-infiltrating microglia were characterised for molecules involved in antigen presentation and cytotoxic activity. As comparison, PBR was investigated in three brains with multiple sclerosis (MS) and three with Parkinson's disease (PD). The expression profile of four anaplastic astrocytomas was also exploited and results were compared to the profile of eleven samples of normal temporal lobe and nine cases of PD. PET studies showed that [(11)C](R)-PK11195 binding was markedly lower in tumours than in the contralateral grey matter. Pathological investigation revealed that glioma-infiltrating microglia failed to express PBR and cytotoxic molecules although some cells still expressed antigen presenting molecules. PBR and cytotoxic molecules were highly represented in MS and PD. Evaluation of microarray datasets confirmed these differences. Our results demonstrated PBR suppression in glioma-infiltrating microglia and suggested that PBR may have a relevant role in modulating the anti-tumour inflammatory response in astrocytic tumours

Asymmetric projections of the arcuate fasciculus to the temporal cortex underlie lateralized language function in the human brain

The arcuate fasciculus (AF) in the human brain has asymmetric structural properties. However, the topographic organization of the asymmetric AF projections to the cortex and its relevance to cortical function remain unclear. Here we mapped the posterior projections of the human AF in the inferior parietal and lateral temporal cortices using surface-based structural connectivity analysis based on diffusion MRI and investigated their hemispheric differences. We then performed the cross-modal comparison with functional connectivity based on resting-state functional MRI (fMRI) and task-related cortical activation based on fMRI using a semantic classification task of single words. Structural connectivity analysis showed that the left AF connecting to Broca's area predominantly projected in the lateral temporal cortex extending from the posterior superior temporal gyrus to the mid part of the superior temporal sulcus and the middle temporal gyrus, whereas the right AF connecting to the right homolog of Broca's area predominantly projected to the inferior parietal cortex extending from the mid part of the supramarginal gyrus to the anterior part of the angular gyrus. The left-lateralized projection regions of the AF in the left temporal cortex had asymmetric functional connectivity with Broca's area, indicating structure-function concordance through the AF. During the language task, left-lateralized cortical activation was observed. Among them, the brain responses in the temporal cortex and Broca's area that were connected through the left-lateralized AF pathway were specifically correlated across subjects. These results suggest that the human left AF, which structurally and functionally connects the mid temporal cortex and Broca's area in asymmetrical fashion, coordinates the cortical activity in these remote cortices during a semantic decision task. The unique feature of the left AF is discussed in the context of the human capacity for language

Network specific change in white matter integrity in mesial temporal lobe epilepsy

学位論文(出版社版): http://hdl.handle.net/2433/226747Objectives: To identify the specific change of white matter integrity that occurs in the brain network related to epileptic activity in patients with mesial temporal lobe epilepsy (MTLE). Methods: We recruited 18 patients with MTLE and 18 healthy subjects. In MTLE patients, the remote functional-deficit zone was delineated using fluorodeoxyglucose positron emission tomography as an extratemporal region showing glucose hypometabolism. Using diffusion magnetic resonance imaging tractography, we defined a seizure propagation tract (PT) as a white matter pathway that connects the focus with a remote functional deficit zone. We also used the corticospinal tract (CST) and inferior longitudinal fasciculus (ILF) as control tracts in the hemisphere ipsilateral to the focus. Fractional anisotropy (FA), mean diffusivity (MD), and volume of the tracts were compared among PT, CST, and ILF. Results: Tractographic analysis identified the uncinate fasciculus, arcuate fasciculus, and fornix as PTs. A decrease in FA was found in MTLE patients compared with healthy subjects in all tracts, but PTs showed a more significant decrease in FA than did the two control tracts. Although the change in MD was also found in MTLE patients compared with healthy controls, a tract-specific change was not observed. Although white-matter damage was observed in all candidate tracts examined, the integrity of white matter was most significantly decreased in PTs in MTLE. Conclusion: The change in white matter integrity occurs specifically in the pathways that connect the focus and remote functional deficit zones in patients with MTLE, i.e., the pathways that are assume to be associated with seizure propagation