Macroscale Thalamic Functional Organization Disturbances and Underlying Core Cytoarchitecture in Early-Onset Schizophrenia.

BACKGROUND AND HYPOTHESIS: Schizophrenia is a polygenetic mental disorder with heterogeneous positive and negative symptom constellations, and is associated with abnormal cortical connectivity. The thalamus has a coordinative role in cortical function and is key to the development of the cerebral cortex. Conversely, altered functional organization of the thalamus might relate to overarching cortical disruptions in schizophrenia, anchored in development. STUDY DESIGN: Here, we contrasted resting-state fMRI in 86 antipsychotic-naive first-episode early-onset schizophrenia (EOS) patients and 91 typically developing controls to study whether macroscale thalamic organization is altered in EOS. Employing dimensional reduction techniques on thalamocortical functional connectome (FC), we derived lateral-medial and anterior-posterior thalamic functional axes. STUDY RESULTS: We observed increased segregation of macroscale thalamic functional organization in EOS patients, which was related to altered thalamocortical interactions both in unimodal and transmodal networks. Using an ex vivo approximation of core-matrix cell distribution, we found that core cells particularly underlie the macroscale abnormalities in EOS patients. Moreover, the disruptions were associated with schizophrenia-related gene expression maps. Behavioral and disorder decoding analyses indicated that the macroscale hierarchy disturbances might perturb both perceptual and abstract cognitive functions and contribute to negative syndromes in patients. CONCLUSIONS: These findings provide mechanistic evidence for disrupted thalamocortical system in schizophrenia, suggesting a unitary pathophysiological framework.

The thalamic functional gradient and its relationship to structural basis and cognitive relevance.

The human thalamus is an integrative hub richly connected with cortical networks, involving diverse cognitive functions. Emerging evidence suggests that multiscale structural and functional gradients integrate various information across modalities into an abstract representation. However, the presence of functional gradients in the thalamus and its relationship to structural properties and cognitive functions remain unknown. We estimated the functional gradients of the thalamus in two independent normal cohorts using a novel diffusion embedding analysis. We identified two main axes of the functional connectivity patterns, and examined associations with thalamic anatomy, morphology, intrinsic geometry, and specific behavioral relevance. We found that the dominant gradient indicated a lateral/medial axis across the thalamus and captured associations with anatomical nuclei and gray matter volume. The second gradient was an anterior/posterior axis and provided a behavioral characterization from lower level perception to higher level cognition. Furthermore, these two gradients strongly correlated with spatial distance, indicating the prominence of intrinsic geometry in functional hierarchies. These findings were replicated in an independent dataset. Overall, our findings suggested that macroscale gradients showed a coordination of structural and functional interactions, with hierarchical organization contributing to behavior characterization.

Disconnectivity between the raphe nucleus and subcortical dopamine-related regions contributes altered salience network in schizophrenia.

Numerous studies strongly have suggested the significant role of serotonin in the pathomechanism of schizophrenia. However, few studies have directly explored the altered serotonin function in schizophrenia. In the current study, we explored the altered serotonin function in first-episode treatment-naive patients with schizophrenia with resting-state functional magnetic resonance imaging. A total 42 first-episode treatment-naive patients with schizophrenia and carefully matched healthy controls are included in the study. Considering that the raphe nucleus providing a substantial proportion of the serotonin innervation to the forebrain, the raphe nucleus was chosen as the seed to construct voxel-based functional connectivity (FC) maps. In the results, subcortical dopamine-related regions presented decreased FC with the raphe nucleus, such as the bilateral striatum, pallidum, and thalamus, in patients with schizophrenia. Decreased FC in these regions was significantly correlated with the total negative scores in PANSS. Furthermore, these regions presented with decreased FC connection to salience network. Our results presented that the raphe nucleus played an important role in the dysfunction of subcortical DA-related regions, and contributed to the altered salience network in schizophrenia. Our study emphasized the importance of the raphe nucleus in the pathophysiology of schizophrenia.

Six new cycloartane triterpene glycosides from Actaea asiatica.

Six new cycloartane triterpene glycosides, (3',12beta)-O-diacetyl-cimigenol-3-O-beta-D-xylopyranoside (1), (4',25)-O-diacetyl-cimigenol-3-O-beta-D-xylopyranoside (2), 2'-O-acetyl-25-O-methyl-cimigenol-3-O-beta-D-xylopyranoside (3), 2'-O-acetyl-25-O-ethyl-cimigenol-3-O-beta-D-xylopyranoside (4), 3'-O-acetyl-cimicifugoside (5), and 4'-O-acetyl-23-epi-26-deoxycimifugoside (6), were isolated from the rhizomes of Actaea asiatica. Their structures were elucidated on the basis of chemical methods and spectroscopic analysis. Compounds 1, 2, 4-6 exhibited positive cytotoxic activities.

[A new cycloartane triterpene saponin from rhizome of Actaea asiatica].

OBJECTIVE: To isolate and elucidate the chemical constituents with the cytotoxicity activity from the rhizome of Actaea asiatica. METHOD: The chemical constituents were isolated by repeated column chromatography (Toyopearl HW40C and preparative HPLC) and the structure of compound 1 was elucidated by spectral data analysis. RESULT: A cycloartane triterpene saponin com- pound was isolated and identified to be (23R)-16beta, 23: 23alpha, 26: 24alpha: 25-triepoxy-9, 19-cyclolanost-7-en-3beta-O-beta-D-xylopyranoside. CONCLUSION: Compound 1 was a new compound and named (23R)-26-deoxycimicifugoside. The IC50 values of compound 1 for cell growth inhibition of Hela and L929 cell lines were 72.24 and 55.97 mg x L(-1), respectively.