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Although semantic system is composed of two distinctive processes (i.e., semantic knowledge and semantic control), it remains unknown in which way these two processes dissociate from each other. Investigating the white matter neuroanatomy underlying these processes helps improve understanding of this question. To address this issue, we recruited brain-damaged patients with semantic dementia (SD) and semantic aphasia (SA), who had selective predominant deficits in semantic knowledge and semantic control, respectively. We built regression models to identify the white matter network associated with the semantic performance of each patient group. Semantic knowledge deficits in the SD patients were associated with damage to the left medial temporal network, while semantic control deficits in the SA patients were associated with damage to the other two networks (left frontal-temporal/occipital and frontal-subcortical networks). The further voxel-based analysis revealed additional semantic-relevant white matter tracts. These findings specify different processing principles of the components in semantic system.

Funder: Chinese Scholarship Council, Funder: National Key R&D Program of China (2016YFC1306305), Funder: ERC grant (GAP: 670428 - BRAIN2MIND_NEUROCOMP), The anterior temporal lobes (ATL) have become a key brain region of interest in cognitive neuroscience founded upon neuropsychological investigations of semantic dementia (SD). The purposes of this investigation are to generate a single unified model that captures the known cognitive-behavioural variations in SD and map these to the patients’ distribution of frontotemporal atrophy. Here we show that the degree of generalised semantic impairment is related to the patients’ total, bilateral ATL atrophy. Verbal production ability is related to total ATL atrophy as well as to the balance of left > right ATL atrophy. Apathy is found to relate positively to the degree of orbitofrontal atrophy. Disinhibition is related to right ATL and orbitofrontal atrophy, and face recognition to right ATL volumes. Rather than positing mutually-exclusive sub-categories, the data-driven model repositions semantics, language, social behaviour and face recognition into a continuous frontotemporal neurocognitive space.

Although the human temporal lobe has been documented to participate in semantic processing of both verbal and nonverbal stimuli, the exact neural basis underlying the common and unique processing of the two modalities is unclear. Semantic dementia (SD), a disease with a semantic-selective deficit due to predominant temporal lobe atrophy is an ideal lesion model to address this issue. However, many previous studies of SD used an impure patient sample or did not appropriately control for common components between tasks. To overcome these limitations, the present study aims to identify amodal semantic hubs and modality-specific regions in the temporal lobe by investigating behavioral performance on a verbal modality task (word associative matching) and a nonverbal modality task (picture associative matching) and neuroimaging data in 33 SD patients. We found that the left anterior fusiform gyrus was an amodal semantic hub whose gray matter volume correlated significantly with both modalities. We also observed two verbal modality-specific regions (the left posterior inferior temporal gyrus and the left middle superior temporal gyrus) and a nonverbal modality-specific region (the right lateral anterior middle temporal gyrus) whose gray matter volume correlated significantly with one modality when performance on the other modality was partialled out. The results remained significant when we excluded a wide range of potential confounding variables. Furthermore, to confirm the observed effects, we compared the performance of left- and right-hemispheric-predominant atrophic patients on the verbal and nonverbal tasks. The left-predominant patients showed more severe deficits in performance of the verbal task than the right-predominant patients, whereas the two groups of patients presented comparable deficits in the performance of the nonverbal task. These findings refined the structure of semantic network in the temporal lobe, deepening our understanding of the critical role of the temporal lobe in semantic processing.

Background Semantic dementia (SD) is characterized by a selective decline in semantic processing. Although the neuropsychological pattern of this disease has been identified, its topological global alterations and symptom-relevant modules in the whole-brain anatomical network have not been fully elucidated. Objective This study aims to explore the topological alteration of anatomical network in SD and reveal the modules associated with semantic deficits in this disease. Methods We first constructed the whole-brain white-matter networks of 20 healthy controls and 19 patients with SD. Then, the network metrics of graph theory were compared between these two groups. Finally, we separated the network of SD patients into different modules and correlated the structural integrity of each module with the severity of the semantic deficits across patients. Results The network of the SD patients presented a significantly reduced global efficiency, indicating that the long-distance connections were damaged. The network was divided into the following four distinctive modules: the left temporal/occipital/parietal, frontal, right temporal/occipital, and frontal/parietal modules. The first two modules were associated with the semantic deficits of SD. Conclusion These findings illustrate the skeleton of the neuroanatomical network of SD patients and highlight the key role of the left temporal/occipital/parietal module and the left frontal module in semantic processing.

Lin Huang,1 Ke-Liang Chen,1 Bi-Ying Lin,1 Le Tang,1 Qian-Hua Zhao,1 Ying-Ru Lv,2,* Qi-Hao Guo1,* 1Department of Neurology, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China; 2Department of Radiology, Huashan Hospital, Fudan University, Shanghai, China *These authors contributed equally to this work Objectives: To find out whether the Chinese version of Montreal Cognitive Assessment Basic (MoCA-BC) and its subtests could be applied in discrimination among cognitively normal controls (NC), mild cognitive impairment (MCI), mild and moderate Alzheimer’s Disease (AD), and furthermore, to determine the optimal cutoffs most sensitive to distinguish between them.Design: A cross-sectional validation study.Setting: Huashan Hospital, Shanghai, China.Participants: There was a total of 1,969 participants: individuals with MCI (n=663), mild (n=345), moderate (n=441) AD, and cognitively NC (n=520) were recruited from the Memory Clinic, Huashan Hospital, Shanghai, China.Measurements: Baseline MoCA-BC scores were collected from firsthand data. Two subtests were calculated from MoCA-BC: the Memory Index Score of MoCA-BC (MoCA-BC-MIS) and the Non-memory Index Score of MoCA-BC (MoCA-BC-NM).Results: MoCA-BC was an effective cognitive tool to discriminate among NC, MCI, mild and moderate AD in the Chinese elderly across all education groups, implying that it was efficient not only for detecting MCI, but for different severities of AD as well. For MCI screening, the total score of MoCA-BC (MoCA-BC-T) and MoCA-BC-MIS had similar high sensitivity and specificity. For discrimination among MCI, mild and moderate AD, the MoCA-BC-T and MoCA-BC-NM had similar performance.Conclusion: MoCA-BC is an effective cognitive test to distinguish between NC, MCI, mild and moderate AD among the Chinese elderly with various levels of education. Keywords: mild cognitive impairment, Montreal Cognitive Assessment, Alzheimer’s disease, cutoff study

Individuals with semantic dementia (SD) typically suffer from selective semantic deficits due to degenerative brain atrophy. Although some brain regions have been found to be correlated with the semantic impairments of SD patients, it is unclear if the damage is actually responsible for SD patients’ semantic disorders because these findings were primarily obtained by examining the roles of local individual regions themselves without considering the influence of other regions that are functionally or structurally connected to the local individual regions. To resolve this problem, we investigated, from the brain network perspective, the relationship between the brain-network measures of regions and connections with semantic performance in 17 SD patients. We found that the severity of semantic deficits of SD patients was significantly correlated with the degree centrality values of the left anterior hippocampus (aHIP). Moreover, the semantic performance of the patients was also significantly correlated with the strength of gray matter functional connectivity of this region and two other regions: the left temporal pole/insula (TP/INS) and the left middle temporal gyrus. We further observed that the strength of the white matter structural connectivity of the left aHIP-left TP/INS tract could effectively predict the semantic performance of SD patients. When we controlled for a wide range of potential confounding factors (e.g., total gray matter volume), the above effects still held well. These findings revealed the critical brain network with the left aHIP as the center that could be contributing to the semantic impairments of SD.

Given that extensive cerebral regions are co-atrophic in semantic dementia (SD), it is not yet known which critical regions (SD-semantic-critical regions) are really responsible for the semantic deficits of SD. To identify the SD-semantic-critical regions, we explored the relationship between the degree of cerebral atrophy in the whole brain and the severity of semantic deficits in 19 individuals with SD. We found that the gray matter volumes of two regions [left fusiform gyrus (lFFG) and left parahippocampal gyrus (lPHG)] significantly correlated with the semantic scores of patients with SD. Importantly, the effects of the lFFG remained significant after controlling for the gray matter volumes of the lPHG. Moreover, the effects of the region could not be accounted for by the total gray matter volume, general cognitive ability, laterality of brain atrophy, or control task performance. We further observed that each atrophic portion of the lFFG along the anterior-posterior axis might dedicate to the loss of semantic functions in SD. These results reveal that the lFFG could be a critical region contributing to the semantic deficits of SD.