Aberrant brain functional connectivity mediates the effects of negative symptoms on cognitive function in schizophrenia: A structural equation model.

BACKGROUND: Schizophrenia is a severe psychiatric disorder, characterized by positive symptoms, negative symptoms, and cognitive deficits. Elucidating the mechanism of negative symptom and cognitive deficits could contribute to the treatment and prognosis of schizophrenia. We hypothesized that abnormal functional connectivity would be involved in the indirect effects of negative symptoms on cognitive function. METHODS: A total of 150 schizophrenia male patients and 108 healthy controls matched for age, education and gender were enrolled in the study. The scores of Brief Negative Symptom Scale were divided into two factors: motivation and pleasure deficits (MAP) and diminished expression (EXP). Subsequently, a series of classic neurocognitive tests were used to evaluate cognitive functions. Resting-state fMRI data was collected from all participants. The Anatomical Automatic Labeling template was employed to establish regions of interest, thereby constructing the functional connectivity network across the entire brain. Eventually, scores of patients' negative symptoms scale, cognitive function, and strengths of abnormal functional connectivity were incorporated into a structural equation model to explore the interactions among variables. RESULTS: MAP exhibited a distinctly and significantly negative impact on cognitive function. The functional connectivity between the left insula and left precuneus, along with that between the left precuneus and right angular gyrus, collectively served as intermediaries, contributing to the indirect effects of MAP and EXP on cognitive function. CONCLUSIONS: Our findings demonstrated the moderating role of aberrant brain functional connectivity between negative symptoms and cognitive function, providing clues about the neural correlates of negative symptoms and cognitive deficits in schizophrenia.

Polygenic effects on brain functional endophenotype for deficit and non-deficit schizophrenia.

Deficit schizophrenia (DS) is a subtype of schizophrenia (SCZ). The polygenic effects on the neuroimaging alterations in DS still remain unknown. This study aims to calculate the polygenic risk scores for schizophrenia (PRS-SCZ) in DS, and further explores the potential associations with functional features of brain. PRS-SCZ was calculated according to the Whole Exome sequencing and Genome-wide association studies (GWAS). Resting-state fMRI, as well as biochemical features and neurocognitive data were obtained from 33 DS, 47 NDS and 41 HCs, and association studies of genetic risk with neuroimaging were performed in this sample. The analyses of amplitude of low-frequency fluctuation (ALFF), regional homogeneity (ReHo) and functional connectivity (FC) were performed to detect the functional alterations between DS and NDS. In addition, correlation analysis was used to investigate the relationships between functional features (ALFF, ReHo, FC) and PRS-SCZ. The PRS-SCZ of DS was significantly lower than that in NDS and HC. Compared to NDS, there was a significant increase in the ALFF of left inferior temporal gyrus (ITG.L) and left inferior frontal gyrus (IFG.L) and a significant decrease in the ALFF of right precuneus (PCUN.R) and ReHo of right middle frontal gyrus (MFG.R) in DS. FCs were widely changed between DS and NDS, mainly concentrated in default mode network, including ITG, PCUN and angular gyrus (ANG). Correlation analysis revealed that the ALFF of left ITG, the ReHo of right middle frontal gyrus, the FC value between insula and ANG, left ITG and right corpus callosum, left ITG and right PCUN, as well as the scores of Trail Making Test-B, were associated with PRS-SCZ in DS. The present study demonstrated the differential polygenic effects on functional changes of brain in DS and NDS, providing a potential neuroimaging-genetic perspective for the pathogenesis of schizophrenia.

Aberrant Functional Connectivity of the Orbitofrontal Cortex Is Associated With Excited Symptoms in First-Episode Drug-Naïve Patients With Schizophrenia.

Background: Schizophrenia (SZ) is associated with the highest disability rate among serious mental disorders. Excited symptoms are the core symptoms of SZ, which appear in the early stage, followed by other stages of the disease subsequently. These symptoms are destructive and more prone to violent attacks, posing a serious economic burden to the society. Abnormal spontaneous activity in the orbitofrontal cortex had been reported to be associated with excited symptoms in patients with SZ. However, whether the abnormality appears in first-episode drug-naïve patients with SZ has still remained elusive. Methods: A total of 56 first-episode drug-naïve patients with SZ and 27 healthy controls underwent resting-state functional magnetic resonance imaging (rs-fMRI) and positive and negative syndrome scale (PANSS). First, differences in fractional amplitude of low-frequency fluctuations (fALFF) between first-episode drug-naïve patients with SZ and healthy controls were examined to identify cerebral regions exhibiting abnormal local spontaneous activity. Based on the fALFF results, the resting-state functional connectivity analysis was performed to determine changes in cerebral regions exhibiting abnormal local spontaneous activity. Finally, the correlation between abnormal functional connectivity and exciting symptoms was analyzed. Results: Compared with the healthy controls, first-episode drug-naïve patients with SZ showed a significant decrease in intrinsic activity in the bilateral precentral gyrus, bilateral postcentral gyrus, and the left orbitofrontal cortex. In addition, first-episode drug-naïve patients with SZ had significantly reduced functional connectivity values between the left orbitofrontal cortex and several cerebral regions, which were mainly distributed in the bilateral postcentral gyrus, the right middle frontal gyrus, bilateral paracentral lobules, the left precentral gyrus, and the right median cingulate. Further analyses showed that the functional connectivity between the left orbitofrontal cortex and the left postcentral gyrus, as well as bilateral paracentral lobules, was negatively correlated with excited symptoms in first-episode drug-naïve patients with SZ. Conclusion: Our results indicated the important role of the left orbitofrontal cortex in first-episode drug-naïve patients with SZ and suggested that the abnormal spontaneous activity of the orbitofrontal cortex may be valuable to predict the occurrence of excited symptoms. These results may provide a new direction to explore the excited symptoms of SZ.

Facial emotion perception abilities are related to grey matter volume in the culmen of cerebellum anterior lobe in drug-naïve patients with first-episode schizophrenia.

Impaired capability for understanding and interpreting the expressions on other people's faces manifests itself as a core feature of schizophrenia, contributing to social dysfunction. With the purpose of better understanding of the neurobiological basis of facial emotion perception deficits in schizophrenia, we investigated facial emotion perception abilities and regional structural brain abnormalities in drug-naïve patients with first-episode schizophrenia, and then examined the correlation between them. Fifty-two drug-naive patients with first-episode schizophrenia and 29 group-matched healthy controls were examined for facial emotion perception abilities assessed with the Facial Emotion Categorization and performed magnetic resonance imaging. The Facial Emotion Categorization data were inserted into a logistic function model so as to calculate shift point and slope as outcome measurements. Voxel-based morphometry was applied to investigate regional grey matter volume (GMV) alterations. The relationship between facial emotion perception and GMV was explored in patients using voxel-wise correlation analysis within brain regions that showed a significant GMV alterations in patients compared with controls. The schizophrenic patients performed differently on Facial Emotion Categorization tasks from the controls and presented a higher shift point and a steeper slope. Relative to the controls, patients showed GMV reductions in the superior temporal gyrus, middle occipital gyrus, parahippocampa gyrus, posterior cingulate, the culmen of cerebellum anterior lobe, cerebellar tonsil, and the declive of cerebellum posterior lobe. Importantly, abnormal performance on Facial Emotion Categorization was found correlated with GMV alterations in the culmen of cerebellum anterior lobe in schizophrenia. This study suggests that reduced GMV in the culmen of cerebellum anterior lobe occurs in first-episode schizophrenia, constituting a potential neuropathological basis for the impaired facial emotion perception in schizophrenia.

Abnormalities of regional homogeneity and its correlation with clinical symptoms in Naïve patients with first-episode schizophrenia.

Several resting-state neuroimaging studies have indicated abnormal regional homogeneity (ReHo) in chronic schizophrenia; however, little work has been conducted to investigate naïve patients with first-episode schizophrenia (FES). Even less investigated is the association between ReHo measures and clinical symptom severity in naïve patients with FES. The current study evaluated ReHo alterations in whole brain, and assessed the correlations between ReHo measures and clinical variables in naïve patients with FES. Forty-four naïve patients with FES and 26 healthy controls (HC) underwent resting-state functional magnetic resonance imaging (rs-fMRI). Group-level analysis was utilized to analyze the ReHo differences between FES and HC in a voxel-by-voxel manner. Severity of symptoms was evaluated using a five-factor model of the Positive and Negative Syndrome Scale (PANSS). The correlation between the severity of symptoms and ReHo map was examined in patients using voxel-wise correlation analyses within brain areas that showed a significant ReHo alteration in patients compared with controls. Compared with the healthy control group, the FES group showed a significant decrease in ReHo values in the left medial frontal gyrus (MFG), right precentral gyrus, left superior temporal gyrus (STG), left left middle temporal gyrus (MTG), left thalamus, and significant increase in ReHo values in the left MFG, left inferior parietal lobule (IPL), left precuneus, and right lentiform nucleus (LN). In addition, the correlation analysis showed the PANSS total score negatively correlated with ReHo in the right precentral gyrus and positively correlated with ReHo in the left thalamus, the positive factor positively correlated with ReHo in the right thalamus, the disorganized/concrete factor positively correlated with ReHo in left posterior cingulate gyrus (PCG), the excited factor positively correlated with ReHo in the left precuneus, and the depressed factor negatively correlated with ReHo in the right postcentral gyrus and positively correlated with ReHo in the right thalamus. Our results indicate that widespread ReHo abnormalities occurred in an early stage of schizophrenic onset, suggesting a potential neural basis for the pathogenesis and symptomatology of schizophrenia.

An Association Study on the Cognitive Function and the Cerebral Grey Matter Volume of Patients with First-Episode Schizophrenia.

BACKGROUND: The impairment of cognitive function is one of the core symptoms in schizophrenia, and the degree of recovery is closely related to whether patients are able to rejoin society successfully. OBJECTIVE: This study was to clarify the correlation between cognitive function and cerebral grey matter volume in schizophrenia. METHODS: The neuro-cognitive functions of thirty-seven patients with first-episode schizophrenia (the patient group) and thirty healthy controls (the control group) was evaluated with the Clock Drawing Test, Trail Marking Test, Digit Span Test, Auditory Verbal Learning Test, Wisconsin Card Sorting Test, Verbal Fluency Test, Semantic Similarity Test and Stroop Color-Word Test. The facial emotion cognitive task was employed to assess the facial emotion cognitive functions of thirty-two patients with first-episode schizophrenia (the patient group) and 29 healthy controls (the control group). The psychotic symptoms of patients with first-episode schizophrenia were evaluated using the Positive and Negative Syndrome Scale (PANSS). The brain imaging data of the patient group and control group were collected using the magnetic resonance imagine (MRI). RESULTS: The difference between the patient group and the control group in the results of Clock Drawing Test, Trail Marking Test, Digit Span Test, Auditory Verbal Learning Test, Wisconsin Card Sorting Test, Verbal Fluency Test, Semantic Similarity Test and Stroop Color-Word Test's reaction time were significant. These two groups' Slopes in the facial emotion cognitive task were also significantly different from each other. According to the comparison of cerebral grey matter volume between the patient group and the control group, it was found that the grey matter volume of the patient group increased in the left superior frontal gyrus, and decreased in the left occipital gyrus, lingual gyrus and upper cerebellum. Based on the analyses of neuro-cognitive data and brain imaging data of the patient group, the scores of the number of correct responses in Stroop Color-Word Test's Card C were negatively correlated with grey matter volumes of the left upper frontal gyrus, right upper frontal gyrus and middle frontal gyrus. The analyses on the facial emotion cognitive task and brain imaging data of the patient group showed that the slope data were positively correlated with grey matter volumes of the right superior temporal gyrus, middle temporal gyrus, left middle temporal gyrus, inferior temporal gyrus and fusiform gyrus. CONCLUSION: There are general impairments in the neuro-cognitive functions and facial emotion cognitive functions of patients with first-episode schizophrenia, and the results suggest that brain areas with abnormal grey matter volumes are likely to be the brain structure and functional basis of the cognitive impairments.

Alcoholism Detection by Data Augmentation and Convolutional Neural Network with Stochastic Pooling.

Alcohol use disorder (AUD) is an important brain disease. It alters the brain structure. Recently, scholars tend to use computer vision based techniques to detect AUD. We collected 235 subjects, 114 alcoholic and 121 non-alcoholic. Among the 235 image, 100 images were used as training set, and data augmentation method was used. The rest 135 images were used as test set. Further, we chose the latest powerful technique-convolutional neural network (CNN) based on convolutional layer, rectified linear unit layer, pooling layer, fully connected layer, and softmax layer. We also compared three different pooling techniques: max pooling, average pooling, and stochastic pooling. The results showed that our method achieved a sensitivity of 96.88%, a specificity of 97.18%, and an accuracy of 97.04%. Our method was better than three state-of-the-art approaches. Besides, stochastic pooling performed better than other max pooling and average pooling. We validated CNN with five convolution layers and two fully connected layers performed the best. The GPU yielded a 149× acceleration in training and a 166× acceleration in test, compared to CPU.

Reduced white matter integrity and facial emotion perception in never-medicated patients with first-episode schizophrenia: A diffusion tensor imaging study.

BACKGROUND: Facial emotion perception is impaired in schizophrenia. Although the pathology of schizophrenia is thought to involve abnormality in white matter (WM), few studies have examined the correlation between facial emotion perception and WM abnormalities in never-medicated patients with first-episode schizophrenia. The present study tested associations between facial emotion perception and WM integrity in order to investigate the neural basis of impaired facial emotion perception in schizophrenia. METHODS: Sixty-three schizophrenic patients and thirty control subjects underwent facial emotion categorization (FEC). The FEC data was inserted into a logistic function model with subsequent analysis by independent-samples T test and the shift point and slope as outcome measurements. Severity of symptoms was measured using a five-factor model of the Positive and Negative Syndrome Scale (PANSS). Voxelwise group comparison of WM fractional anisotropy (FA) was operated using tract-based spatial statistics (TBSS). The correlation between impaired facial emotion perception and FA reduction was examined in patients using simple regression analysis within brain areas that showed a significant FA reduction in patients compared with controls. The same correlation analysis was also performed for control subjects in the whole brain. RESULTS: The patients with schizophrenia reported a higher shift point and a steeper slope than control subjects in FEC. The patients showed a significant FA reduction in left deep WM in the parietal, temporal and occipital lobes, a small portion of the corpus callosum (CC), and the corona radiata. In voxelwise correlation analysis, we found that facial emotion perception significantly correlated with reduced FA in various WM regions, including left forceps major (FM), inferior longitudinal fasciculus (ILF), inferior fronto-occipital fasciculus (IFOF), Left splenium of CC, and left ILF. The correlation analyses in healthy controls revealed no significant correlation of FA with FEC task. CONCLUSIONS: These results showed disrupted WM integrity in these regions constitutes a potential neural basis for the facial emotion perception impairments in schizophrenia.