BackgroundA lack of a sufficiently large sample at single sites causes poor generalizability in automatic diagnosis classification of heterogeneous psychiatric disorders such as schizophrenia based on brain imaging scans. Advanced deep learning methods may be capable of learning subtle hidden patterns from high dimensional imaging data, overcome potential site-related variation, and achieve reproducible cross-site classification. However, deep learning-based cross-site transfer classification, despite less imaging site-specificity and more generalizability of diagnostic models, has not been investigated in schizophrenia.MethodsA large multi-site functional MRI sample (n = 734, including 357 schizophrenic patients from seven imaging resources) was collected, and a deep discriminant autoencoder network, aimed at learning imaging site-shared functional connectivity features, was developed to discriminate schizophrenic individuals from healthy controls.FindingsAccuracies of approximately 85·0% and 81·0% were obtained in multi-site pooling classification and leave-site-out transfer classification, respectively. The learned functional connectivity features revealed dysregulation of the cortical-striatal-cerebellar circuit in schizophrenia, and the most discriminating functional connections were primarily located within and across the default, salience, and control networks.InterpretationThe findings imply that dysfunctional integration of the cortical-striatal-cerebellar circuit across the default, salience, and control networks may play an important role in the “disconnectivity” model underlying the pathophysiology of schizophrenia. The proposed discriminant deep learning method may be capable of learning reliable connectome patterns and help in understanding the pathophysiology and achieving accurate prediction of schizophrenia across multiple independent imaging sites.

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Auditory verbal hallucinations (AVHs) are a core symptom of schizophrenia, and resistant to antipsychotic medication in a substantial proportion of patients. This study aimed to investigate the neural correlates of AVHs in schizophrenia patients and its response to a modified continuous theta-burst stimulation (cTBS) by transcranial magnetic stimulation. In a cross-sectional experiment, resting-state functional magnetic resonance images were collected from 31 AVH schizophrenia patients, 26 non-AVH schizophrenia patients, and 33 sex-/age-matched healthy controls (HCs). Functional connectivity strength (FCS) maps were compared among groups by 1-way analysis of variance (ANOVA). In a longitudinal experiment, 16 and 11 AVH patients received real and sham cTBS treatment for 15 days, respectively. Notably, this was not a randomized control trail. Changes in AVH and FCS were analyzed by 2-way ANOVA and 2-sample t-test, respectively. In the cross-sectional experiment, comparison of FCS maps identified 8 clusters among groups, but only one cluster (in left cerebellum) differed significantly in AVH patients compared to both HCs and non-AVH patients. In the longitudinal experiment, the real cTBS group showed a greater improvement in symptoms and a larger FCS decrease in left cerebellum than the sham group. Pearson's correlation analysis indicated that baseline FCS of the overlapping cerebellum cluster (between the cross-sectional and longitudinal findings) was negatively correlated with symptom improvement in the real treatment group. These findings emphasize the role of the left cerebellum in both the pathophysiology and clinical treatment of AVHs in schizophrenia patients.

Background:Tamoxifen is the most widely used drug for treating patients with estrogen receptor-sensitive breast cancer. There is evidence that breast cancer patients treated with tamoxifen exhibit cognitive dysfunction. However, the underlying neural mechanism remains unclear. The present study aimed to investigate the neural mechanisms underlying working memory deficits in combination with functional connectivity changes in premenopausal women with breast cancer who received long-term tamoxifen treatment.Methods:A total of 31 premenopausal women with breast cancer who received tamoxifen and 32 matched healthy control participants were included. The participants completed n-back tasks and underwent resting-state functional magnetic resonance imaging, which measure working memory performance and brain functional connectivity, respectively. A seed-based functional connectivity analysis within the whole brain was conducted, for which the dorsolateral prefrontal cortex was chosen as the seed region.Results:Our results indicated that the tamoxifen group had significant deficits in working memory and general executive function performance and significantly lower functional connectivity of the right dorsolateral prefrontal cortex with the right hippocampus compared with the healthy controls. There were no significant changes in functional connectivity in the left dorsolateral prefrontal cortex within the whole brain between the tamoxifen group and healthy controls. Moreover, significant correlations were found in the tamoxifen group between the functional connectivity strength of the dorsolateral prefrontal cortex with the right hippocampus and decreased working memory performance.Conclusion:This study demonstrates that the prefrontal cortex and hippocampus may be affected by tamoxifen treatment, supporting an antagonistic role of tamoxifen in the long-term treatment of breast cancer patients.

These results suggest that the functional disconnection in MTL subsystem of the DMN may have association with attention function of BC after chemotherapy.

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Previous studies have reported that trait anxiety (TA) affects decision making. However, results remain largely inconsistent across studies. The aim of the current study was to further address the interaction between TA and decision making. 304 subjects without depression from a sample consisting of 642 participants were grouped into high TA (HTA), medium TA (MTA) and low TA (LTA) groups based on their TA scores from State Trait Anxiety Inventory. All subjects were assessed with the Iowa Gambling Task (IGT) that measures decision making under ambiguity and the Game of Dice Task (GDT) that measures decision making under risk. While the HTA and LTA groups performed worse on the IGT compared to the MTA group, performances on the GDT between the three groups did not differ. Furthermore, the LTA and HTA groups showed different individual deck level preferences in the IGT: the former showed a preference for deck B indicating that these subjects focused more on the magnitude of rewards, and the latter showed a preference for deck A indicating significant decision making impairment. Our findings suggest that trait anxiety has effect on decision making under ambiguity but not decision making under risk and different levels of trait anxiety related differently to individual deck level preferences in the IGT.

Objectives: Binocular rivalry is a typical example of bistable perception that arises when two monocular images are simultaneously presented to each eye. Binocular rivalry is a heritable perceptual cognitive function that is impaired in patients with schizophrenia (SZ). Despite its potential suitability as a visual endophenotype, binocular rivalry has hardly been studied in the unaffected siblings of schizophrenia (SIB). There is also little research about whether binocular rivalry is a potential visual endophenotype between SZ and SIB.Methods: In our cross-sectional study, we included 40 SZ and their unaffected SIBs, as well as 40 age- and sex-matched healthy controls (HC). All subjects underwent the binocular rivalry test, the Positive and Negative Syndrome Scale (PANSS) and a battery of cognitive neuropsychological assessments evaluating attention, memory and executive function domains.Results: Our results demonstrate that the switching rate in SZ was significantly slower than in HC (p < 0.001), and compared to the SIB, the mean alternation rates were significantly different (p < 0.01). Moreover, there was a significant difference in mean switching rate between the SIB and the HC (p < 0.001). There was no significant correlation between the alternation rate of binocular rivalry and these cognitive tasks and the PANSS scores.Conclusion: The present study shows that SZ and SIB both exhibit changes in binocular rivalry, with SIB exhibiting intermediate performance compared with that of SZ and the HC. This supports the claim that the switching rate for SZ differs from that of SIB and suggests that binocular rivalry may qualify as a visual endophenotype for SZ.