Altered Functional Connectivity of the Thalamus Subregions Associated with Impaired Attention After Sleep Deprivation.

Objective: The thalamus plays a critical role in attentional maintenance. Previous studies have revealed the dysfunction of the thalamus in attention decline after acute sleep deprivation (SD). However, the functional connectivity (FC) between the thalamus subregions and cortical regions underlying attentional impairment after acute SD remains unclear. Here, we aimed to probe the relationship between attentional function and the altered thalamocortical FC after acute SD. Methods: In this study, 25 healthy participants with regular sleep conducted an attentional network test and received a resting-state fMRI scan before and after 24 hours of SD. Then, we analyzed the FC between the thalamus and cerebrum and relationships with attentional function in the enrolled subjects. Results: Our results showed that the participants showed a significantly lower alerting effect, a higher executive effect, and lower accuracy after acute SD. Compared to the rested wakefulness state, we observed decreased FCs between the "somatosensory" thalamic seed and left frontal pole, right frontal pole, left middle temporal gyrus (posterior division), and right middle temporal gyrus (posterior division). Furthermore, the reduced FC between the right middle temporal gyrus and "somatosensory" thalamic seed was negatively associated with the change in orienting effect of the participants. Conclusion: Our findings reveal that the disrupted FC between thalamus subregions and cortical regions may contribute to impaired attention after SD.

The role of the immune system in depersonalisation disorder.

OBJECTIVES: Depersonalisation-derealization disorder (DPD) is a dissociative disorder that impairs cognitive function and occupational performance. Emerging evidence indicate the levels of tumour necrosis factor-α and interleukin associated with the dissociative symptoms. In this study, we aimed to explore the role of the immune system in the pathology of DPD. METHODS: We screened the protein expression in serum samples of 30 DPD patients and 32 healthy controls. Using a mass spectrometry-based proteomic approach, we identified differential proteins that were verified in another group of 25 DPD patients and 30 healthy controls using immune assays. Finally, we performed a correlation analysis between the expression of differential proteins and clinical symptoms of patients with DPD. RESULTS: We identified several dysregulated proteins in patients with DPD compared to HCs, including decreased levels of C-reactive protein (CRP), complement C1q subcomponent subunit B, apolipoprotein A-IV, and increased levels of alpha-1-antichymotrypsin (SERPINA3). Moreover, the expression of CRP was positively correlated with visuospatial memory and the ability to inhibit cognitive interference of DPD. The expression of SERPINA3 was positively correlated with the ability to inhibit cognitive interference and negatively correlated with the perceptual alterations of DPD. CONCLUSIONS: The dysregulation of the immune system may be the underlying biological mechanism in DPD. And the expressions of CRP and SERPINA3 can be the potential predictors for the cognitive performance of DPD.

How BDNF affects working memory in acute sleep deprivation: The mediating role of spontaneous brain activity.

The brain-derived neurotrophic factor (BDNF) mediates the plasticity associated with memory processing, and compensatorily increases after acute sleep deprivation (SD). However, whether the altered spontaneous brain activity mediates the association between BDNF and working memory in SD remains unknown. Here, we aimed to probe the mediating role of the spontaneous brain activity between plasma BDNF and WM function in SD. A total of 30 healthy subjects with regular sleep were enrolled in this study. Resting-sate functional magnetic resonance imaging (fMRI) scans and the peripheral blood were collected before and after 24 h SD. All participants also received n-back task assessing working memory (WM) performance. The amplitude of low-frequency fluctuation (ALFF) and fractional ALFF (fALFF) were calculated to reflect the intensity of regional spontaneous brain activity. Plasma BDNF was measured by sandwich ELISA. Our results revealed a significant decline in WM and increase in plasma BDNF level after SD, and negative association between the changed WM performance and plasma BDNF level. Specially, the ALFF of the left inferior parietal cortex and right inferior frontal cortex, and fALFF of the left anterior cingulate and medial prefrontal cortex and left posterior opercular cortex regulated the association between the BDNF and one-back reaction time respectively. Our results suggest that the association between BDNF and working memory may be mediated through regional spontaneous brain activity involving in the cerebral cortex, which may provide new sight into the interaction between neurotrophic factors and cognition, and potential targets for noninvasive brain stimulation on WM decline after acute SD.

Effects of aripiprazole on resting-state functional connectivity of large-scale brain networks in first-episode drug-naïve schizophrenia patients.

Aripiprazole modulates functional connectivity (FC) between several brain regions in first-episode schizophrenia patients, contributing to improvement in clinical symptoms. However, the effects of aripiprazole on abnormal connections among extensive brain networks in schizophrenia patients remain unclear. We aimed to investigate the effects of 12 weeks of aripiprazole treatment on the FC of large-scale brain networks. Forty-five first-episode drug-naïve schizophrenia patients and 45 healthy controls were recruited for this longitudinal study. Resting-state functional magnetic resonance imaging (fMRI) data were collected at baseline and after 12 weeks of aripiprazole treatment. The patients were classified into those in response (SCHr group) and non-response (SCHnr group) according to the improvement of clinical symptoms after 12-weeks treatment. The FC were evaluated for seven large-scale brain networks. In addition, correlation analysis was performed to investigate associations between changes FC of large-scale brain networks and clinical symptoms. Before aripiprazole treatment, schizophrenia patients showed decreased FC of extensive brain networks compared to healthy controls. The 12-week aripiprazole treatment significantly prevented the constantly decreased FC of subcortical network, default mode network and other brain networks in patients with SCHr, in association with the improvement of clinical symptoms. Taken together, these findings have revealed the effects of aripiprazole on FC in large-scale networks in schizophrenia patients, which could provide new insight on interpreting symptom improvement in SCH.

Altered Functional Connectivity in Working Memory Network After Acute Sleep Deprivation.

Acute sleep deprivation (SD) has a detrimental effect on working memory (WM). However, prior functional magnetic resonance imaging (fMRI) studies have failed to reach consistent results on brain functions underlying WM decline after acute SD. Thus, we aimed to identify convergent patterns of abnormal brain functions due to WM decline after acute SD. A coordinate-based activation likelihood estimation (ALE) meta-analysis of task-state fMRI studies testing the effects of acute SD on WM was performed to construct WM network. Then 26 healthy subjects with regular sleep performed the n-back task and underwent resting-state fMRI scanning before and after 24 h of SD. The functional connectivity (FC) among these brain regions and correlations with WM performance were calculated. The ALE results displayed that SD subjects performing WM-related tasks had consistent hypoactivation in the occipital lobe, left middle occipital gyrus, parietal lobe, precuneus, inferior parietal lobule, right sub-gyral, right cuneus, right limbic lobe, and right posterior cingulate. Consistent hyperactivation was showed in the left cerebrum, including the lingual gyrus, posterior lobe, cuneus, temporal lobe, and fusiform gyrus. These identified brain regions as the seeds to construct WM network. The increased FC between the left declive and right sub-gyral, left cuneus and left lingual gyrus, and left cuneus and right post cingulate were found. Furthermore, the impaired WM performance negatively correlated with increased FC. Taken together, our findings highlight that the altered FC in WM network may be the underlying mechanisms of WM decline after acute SD.

Dysfunction of large-scale brain networks underlying cognitive impairments in shift work disorder.

It has been demonstrated that shift work can affect cognitive functions. Several neuroimaging studies have revealed altered brain function and structure for patients with shift work disorder (SWD). However, knowledge on the dysfunction of large-scale brain networks underlying cognitive impairments in shift work disorder is limited. This study aims to identify altered functional networks associated with cognitive declines in shift work disorder, and to assess their potential diagnostic value. Thirty-four patients with shift work disorder and 36 healthy controls (HCs) were recruited to perform the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and resting-state functional scans. After surface-based preprocessing, we calculated within- and between-network functional connectivity (FC) using the Dosenbach atlas. Moreover, correlation analysis was done between altered functional connectivity of large-scale brain networks and scores of cognitive assessments in patients with shift work disorder. Finally, we established a classification model to provide features for patients with shift work disorder concerning the disrupted large-scale networks. Compared with healthy controls, increased functional connectivity within-networks across the seven brain networks, and between-networks involving ventral attention network (VAN)-subcortical network (SCN), SCN-frontoparietal network (FPN), and somatosensory network (SMN)-SCN were observed in shift work disorder. Decreased functional connectivity between brain networks was found in shift work disorder compared with healthy controls, including visual network (VN)-FPN, VN-default mode network (DMN), SMN-DMN, dorsal attention network (DAN)-DMN, VAN-DMN, and FPN-DMN. Furthermore, the altered functional connectivity of large-scale brain networks was significantly correlated with scores of immediate memory, visuospatial, and delayed memory in patients with shift work disorder, respectively. Abnormal functional connectivity of large-scale brain networks may play critical roles in cognitive dysfunction in shift work disorder. Our findings provide new evidence to interpret the underlying neural mechanisms of cognitive impairments in shift work disorder.

Altered Functional Connectivity of Large-Scale Brain Networks in Psychogenic Erectile Dysfunction Associated with Cognitive Impairments.

Purpose: Several studies have demonstrated that psychogenic erectile dysfunction (pED) patients potentially suffer from cognitive dysfunction. Despite that previous neuroimaging studies have reported abnormal functional connections of brain areas associated with cognitive function in pED, the underlying mechanisms of cognitive dysfunction in pED remain elusive. This study aims to investigate the underlying mechanisms of cognitive dysfunction by analyzing large-scale brain networks. Patients and Methods: A total of 30 patients with pED and 30 matched healthy controls (HCs) were recruited in this study and scanned by resting-state functional magnetic resonance imaging. The Dosenbach Atlas was used to define large-scale networks across the brain. The resting-state functional connectivity (FC) within and between large-scale brain networks was calculated to compare pED patients with HCs. The relationship among cognitive performances and altered FC of large-scale brain networks was further explored in pED patients. Results: Our results showed that the decreased FC within visual network, and between visual network and default mode network, visual network and frontoparietal network, and ventral attention and default mode network were found in pED patients. Furthermore, there was a positive correlation between immediate memory score and FC within visual network. The visuospatial score was negatively correlated with decreased FC between ventral attention network and default mode network. Conclusion: Taken together, our findings revealed the relationship between cognitive impairments and altered FC between large-scale brain networks in pED patients, providing the new evidence about the neural mechanisms of cognitive dysfunction in pED patients.

Altered functional connectivity after acute sleep deprivation reveals potential locations for noninvasive brain stimulation techniques.

BACKGROUNDS: Non-invasive brain stimulation (NIBS) techniques are emerging as efficacious treatments for sleep deprivation (SD). However, the stimulation location of NIBS (e.g. transcranial magnetic stimulation and transcranial direct current stimulation) on intervening acute SD is limited in previous studies. In this study, we aimed to investigate potentially effective targets of NIBS on intervening acute SD. METHODS: We firstly performed a meta-analysis of 95 functional magnetic resonance imaging studies to find SD-related brain regions as regions of interest (ROI). Subsequently, we used resting-state functional connectivity analysis in 32 young individuals suffering from 24 h SD to identify brain surface regions associated with the ROIs. Finally, we applied 10-20 system coordinates to locate scalp sites for NIBS corresponding to the brain surface regions. RESULTS: We identified the bilateral dorsolateral prefrontal cortex, bilateral inferior frontal gyrus, left supplementary motor area, precentral, right precuneus, bilateral inferior parietal gyrus, right middle temporal gyrus, and superior frontal gyrus as potential targets of NIBS for intervening SD. The 10-20 system coordinates corresponding to these brain surface regions were identified as potential sites for NIBS. CONCLUSIONS: In conclusion, we identified several potential targets which could provide alternative stimulation locations for the use of NIBS on young patients suffering from acute SD.

Altered White Matter Structural Network Connectivity Associated with Cognitive Declines in Psychogenic Erectile Dysfunction.

It has been reported that individuals with psychogenic erectile dysfunction (pED) potentially suffer from cognitive declines. Despite that increasing neuroimaging studies have demonstrated abnormalities of cerebral structural changes in pED, the association between altered white matter (WM) structural network and cognitive impairments remains unclear. Hence, this study aimed to explore the relationship between WM structural network connectivity and cognitive performance in patients with pED. Forty pED patients and 33 healthy controls (HCs) were recruited to perform cognitive assessments, and diffusion tensor imaging scans. We firstly constructed the WM structural network and applied the machine learning method to identify the important features. Then, we examined group differences in cognitive assessments, WM structural network connectivity within the identified features, and associations between altered WM structural network connectivity and cognitive scores in pED patients. From 26,896 features of DTI data, 24 important features were identified by K-Nearest Neighbor classification with a satisfactory accuracy (78%). Compared with HCs, we found that pED patients showed higher fractional anisotropy (FA) values between left transverse temporal sulcus and left supramarginal gyrus, and lower FA values between left suborbital sulcus and left para-hippocampal part of the medial occipito-temporal gyrus in pED patients. Furthermore, the increased FA between left transverse temporal sulcus and left supramarginal gyrus was observed to be negatively associated with impaired delayed memory. Overall, our findings provide new insights into WM network alterations associated with impaired cognitive functions in pED, which may unravel the potential neural mechanisms underlying the cognitive impairments of pED patients.

Effect of Shi-Zhen-An-Shen herbal formula granule in the treatment of young people at ultra-high risk for psychosis: a pilot study.

Introduction: To date, there is no conclusive evidence for early interventions on ultra-high risk (UHR) for psychosis. The Chinese herbal medicine is confirmed to be beneficial in improving psychiatric symptoms and cognitive impairments for schizophrenia patients. However, the effect of Chinese herbal medicine on treating UHR patients remains unknown. Methods: Eighty UHR patients were recruited from the outpatient department. They were randomly assigned to receive either Shi-Zhen-An-Shen herbal formula granule (SZAS-HFG) combined with aripiprazole placebo or aripiprazole combined with SZAS-HFG placebo for a 12-week treatment. The psychiatric symptoms were assessed using the Structured Interview for Prodromal Syndromes (SIPS). The Trail Making Test part A (TMT-A), Brief Visuospatial Memory Test (BVMT), Hopkins Verbal Learning Test (HVLT), and Continuous Performance Test (CPT) were used to assess cognitive functions. we also employed the Global Assessment of Functioning (GAF) to evaluate social functioning. The linear mixed-effects models were performed to detect the difference in effectiveness between the two groups. Results: After 12-week treatment, both groups showed significant effects of time on SIPS, TMT-A, HVLT, BVMT, and GAF. There was a significant effect of group only on CPT. Moreover, we also found a significant interaction effect on GAF. Conclusion: SZAS-HFG can effectively alleviate psychosis symptoms, and improve cognitive impairments and overall functioning as well as aripiprazole.Clinical trial registration: Chinese Clinical Trial Registry, ChiCTR-IOR-17013513.

Altered functional connectivity of cerebellar networks in first-episode schizophrenia.

Introduction: Abnormalities of the cerebellum have been displayed to be a manifestation of schizophrenia (SCH) which is a detrimental psychiatric disorder. It has been recognized that the cerebellum contributes to motor function, sensorimotor function, cognition, and other brain functions in association with cerebral functions. Multiple studies have observed that abnormal alterations in cerebro-cerebellar functional connectivity (FC) were shown in patients with SCH. However, the FC of cerebellar networks in SCH remains unclear. Methods: In this study, we explored the FC of cerebellar networks of 45 patients with first-episode SCH and 45 healthy control (HC) subjects by using a defined Yeo 17 network parcellation system. Furthermore, we performed a correlation analysis between cerebellar networks' FC and positive and negative symptoms in patients with first-episode SCH. Finally, we established the classification model to provide relatively suitable features for patients with first-episode SCH concerning the cerebellar networks. Results: We found lower between-network FCs between 14 distinct cerebellar network pairs in patients with first-episode SCH, compared to the HCs. Significantly, the between-network FC in N2-N15 was positively associated with positive symptom severity; meanwhile, N4-N15 was negatively associated with negative symptom severity. Besides, our results revealed a satisfactory classification accuracy (79%) of these decreased between-network FCs of cerebellar networks for correctly identifying patients with first-episode SCH. Conclusion: Conclusively, between-network abnormalities in the cerebellum are closely related to positive and negative symptoms of patients with first-episode SCH. In addition, the classification results suggest that the cerebellar networks can be a potential target for further elucidating the underlying mechanisms in first-episode SCH.

Protective Effects of Shi-Zhen-An-Shen Decoction on the Cognitive Impairment in MK801-Induced Schizophrenia Model.

BACKGROUND: Cognitive dysfunction is a core feature of schizophrenia that strongly correlates to the patients' difficulties in independent living and occupational functioning. Synaptic dysfunction may result in cognitive and behavioral changes similar to what have been identified in schizophrenia. Shi-Zhen-An-Shen Decoction (SZASD) is the empirical formula of traditional Chinese medicine adopted in treating psychiatric symptoms, especially the cognitive impairment in schizophrenia patients, with proven efficacy in the long term of clinical practice in Beijing Anding Hospital, Capital Medical University. However, the mechanisms of SZASD on the cognitive improvement in schizophrenia is still unclear. Here, we aim to investigate the underlying mechanisms of the impact of SZASD on the cognitive impairment in MK801-induced schizophrenia-like rats. METHODS: Six rat groups (n = 12 per group) were subjected to different treatments for 14 days. All the six groups were injected intraperitoneally with a given volume of 0.9% saline and MK801 (0.2 mg/kg) for consecutive 14 days for modelling. And the rats in the SZASD-treated groups and the clozapine-treated group were given SZASD (low, middle, and high doses) or clozapine, respectively, by intragastric administration. Then, we performed behavioral tests after the treatments, and the rats were sacrificed on the 19th day for biological analysis. RESULTS: Behavioral tests indicated that SZASD mitigated the aberrant motor activity and improved schizophrenia-like rats' spatial reference memory and sensory gating ability. Furthermore, SZASD significantly increased the expressions of PSD95, BDNF, and synapsin I in the hippocampus of MK801-induced schizophrenia-like rats. CONCLUSIONS: Our findings suggest that SZASD may ameliorate cognitive impairment by restoring the levels of synaptic proteins in the hippocampus.

The altered intrinsic functional connectivity after acupuncture at shenmen (HT7) in acute sleep deprivation.

Introduction: Accumulating evidence has shown that acupuncture could significantly improve the sleep quality and cognitive function of individuals suffering from insufficient sleep. Numerous animal studies have confirmed the effects and mechanisms of acupuncture on acute sleep deprivation (SD). However, the role of acupuncture on individuals after acute SD remains unclear. Methods: In the current study, we recruited 30 healthy subjects with regular sleep. All subjects received resting-state fMRI scans during the rested wakefulness (RW) state and after 24 h of total SD. The scan after 24 h of total SD included two resting-state fMRI sessions before and after needling at Shenmen (HT7). Both edge-based and large-scale network FCs were calculated. Results: The edge-based results showed the suprathreshold edges with abnormal between-network FC involving all paired networks except somatosensory motor network (SMN)-SCN between the SD and RW state, while both decreased and increased between-network FC of edges involving all paired networks except frontoparietal network (FPN)-subcortical network (SCN) between before and after acupuncture at HT7. Compared with the RW state, the large-scale brain network results showed decreased between-network FC in SMN-Default Mode Network (DMN), SMN-FPN, and SMN-ventral attention network (VAN), and increased between-network FC in Dorsal Attention Network (DAN)-VAN, DAN-SMN between the RW state and after 24 h of total SD. After acupuncture at HT7, the large-scale brain network results showed decreased between-network FC in DAN-VAN and increased between-network FC in SMN-VAN. Conclusion: Acupuncture could widely modulate extensive brain networks and reverse the specific between-network FC. The altered FC after acupuncture at HT7 may provide new evidence to interpret neuroimaging mechanisms of the acupuncture effect on acute SD.

Potential Targets for Noninvasive Brain Stimulation on Depersonalization-Derealization Disorder.

INTRODUCTION: Non-invasive brain stimulation seems to be beneficial for DPD patients. However, the sites used in previous studies were empirical. Exploring new stimulation locations via functional magnetic resonance imaging may improve the efficacy. OBJECTIVES: The objective was to find potential locations for non-invasive brain stimulation on the depersonalization-derealization disorder. METHODS: We explored the potential brain surface regions from three pipelines: pipeline 1: activation likelihood estimation meta-analysis (five studies with 36 foci included); pipeline 2: functional connectivity analysis based on DPD-network (76 subjects included); and pipeline 3: functional connectivity analysis based on DPD regions of interest from the meta-analysis. Potential targets were the 10-20 system coordinates for brain surface regions. RESULTS: We identified several potential brain surface regions, including the bilateral medial prefrontal cortex, dorsal lateral prefrontal cortex, superior parietal gyrus, superior temporal gyrus, and right ventrolateral prefrontal cortex as potential sites. CONCLUSION: Our findings of the potential stimulation targets might help clinicians optimize the application of non-invasive brain stimulation therapy in individuals with DPD.

Altered Functional Connectivity and Topological Organization of Brain Networks Correlate to Cognitive Impairments After Sleep Deprivation.

Introduction: Sleep deprivation (SD) has a detrimental effect on cognitive functions. Numerous studies have indicated the mechanisms underlying cognitive impairments after SD in brain networks. However, the findings based on the functional connectivity (FC) and topological architecture of brain networks are inconsistent. Methods: In this study, we recruited 30 healthy participants with regular sleep (aged 25.20 ± 2.20 years). All participants performed the repeatable battery for the assessment of neuropsychological status and resting-state fMRI scans twice, during the rested wakefulness (RW) state and after 24 h of total SD. Using the Dosenbach atlas, both large-scale FC and topological features of brain networks (ie nodal, global and local efficiency) were calculated for the RW and SD states. Furthermore, the correlation analysis was conducted to explore the relationship between the changes in FC and topological features of brain networks and cognitive performances. Results: Compared to the RW state, the large-scale brain network results showed decreased between-network FC in somatomotor network (SMN)-default mode network (DMN), SMN-frontoparietal network (FPN), and SMN-ventral attention network (VAN), and increased between-network FC in the dorsal attention network (DAN)-VAN, DAN-SMN after SD. The clustering coefficient, characteristic path length and local efficiency decreased after SD. Moreover, the decreased attention score positively correlated with the decreased topological measures and negatively correlated with the FC of DAN-SMN. Conclusion: Our results suggested that the increased FC of DAN-SMN and decreased topological features of brain networks may act as neural indicators for the decrease in attention after SD. Clinical Trial Registration: The study was registered at the Chinese Clinical Trial Registry, registration ID: ChiCTR2000039858, China.

White matter abnormalities in first-episode patients with depersonalization/derealization disorder: A tract-based spatial statistics study.

BACKGROUND: Neuroimaging studies on depersonalization / derealization disorder (DPD) have revealed that there are structural and functional alterations across numerous brain regions. However, to date, the exact white matter abnormalities that are associated with different clinical symptoms and cognitive impairments in first-episode, drug-naïve patients with DPD remain unclear. METHODS: Overall, 25 first-episode, drug-naïve patients with DPD and 23 healthy controls were recruited and underwent DTI scans. The tract-based spatial statistics analysis was conducted in order to determine white matter microstructural changes between the two groups. Correlation analysis was conducted between the fractional anisotropy (FA) of abnormal WM fibers and the total score of the 30-item Cambridge Depersonalization Scale (CDS-30), cognitive assessments. RESULTS: Patients with DPD demonstrated higher FA in the right corpus callosum (CC), and posterior corona radiate (CR), compared to healthy controls. The FA in the right CC demonstrated a positive correlation with total score of CDS-30, numbing, unreality of self, perceptual alterations, and temporal disintegration, respectively. FA in the right CR region indicated a positive correlation with the total score of CDS-30, unreality of self, perceptual alterations, and temporal disintegration, respectively. Furthermore, FA in the right CR region was found to be negatively correlated with the Continuous Performance Test and the Stroop color-word test. CONCLUSION: The altered white matter microstructure and cognitive impairments of medication naïve DPD patients were observed. Abnormalities in the integrity of CC and CR were associated with severity of symptoms and cognitive impairments, which may provide a potential biomarker for clinical studies on DPD.

Paliperidone Compared with Haloperidol on the Theory of Mind Tasks in Schizophrenia: A Pilot Trial.

PURPOSE: Theory of mind (ToM) is an important part of social cognitive function and is associated with medial prefrontal cortical (mPFC) activity. This study aimed to evaluate the efficacy of paliperidone in improving ToM task performance in patients with schizophrenia compared with haloperidol. PATIENTS AND METHODS: This study was a single-center, single-blinded (assessor), parallel-group randomized clinical trial of patients with schizophrenia randomized to paliperidone or haloperidol. ToM was assessed at weeks 0, 8, 12, and 16 using the first-order belief, higher-order belief, faux-pas, and Reading the Mind in the Eyes tests. The primary outcome was the change in the ToM performance scores from baseline to after 16 weeks of treatment. RESULTS: The participants received paliperidone (n = 29) or haloperidol (n = 31). For the first-order belief task, there were no between-group differences (P > 0.05) but time differences in both groups (P < 0.05). For the higher-order belief task, there were no between-group differences (P > 0.05), but there were time differences in both groups (P < 0.05) and a time×group interaction in the paliperidone group only (P < 0.05). For the faux-pas task, there was a difference between groups at week 16 (P < 0.05), and the improvement in time was significant for the paliperidone group only (P < 0.05). For the Reading the Mind in the Eyes task, there was an improvement over time for the paliperidone group only (P < 0.05). Safety was manageable in both groups. CONCLUSION: Paliperidone treatment might be more effective than haloperidol in improving ToM task performance in schizophrenia. TRIAL REGISTRATION: chictr.org.cn_identifier ChiCTR-IPR-15007635.

Disrupted Resting-State Functional Connectivity between the Dorsal Attention, Default Mode, and Frontoparietal Networks in Nonorganic Gastrointestinal Disorder Patients with Spleen Deficiency Syndrome.

INTRODUCTION: Spleen deficiency syndrome (SDS), a common clinical syndrome of traditional Chinese medicine, is manifested with digestive symptoms and cognitive impairments. However, the cognitive neural mechanism in brain networks of SDS still remained unclear. Our aim was to investigate the changes between the default mode, dorsal attention, and frontoparietal networks in SDS. METHODS: Twenty nonorganic gastrointestinal disorder (NOGD) patients with SDS and eighteen healthy controls were enrolled to attend functional magnetic resonance imaging scan and participated a continuous performance test (CPT) before scanning. RESULTS: Compared with healthy controls, NOGD patients with SDS showed the significantly increased functional connectivity (FC) between dorsal attention network (DAN) and left frontal-parietal control network (LFPN) and significantly decreased FC between LFPN and default mode network (DMN). The functional network connectivity analysis showed positive correlation coefficients between the DAN and LFPN and DAN and DMN as well as negative correlation between LFPN and DMN in NOGD patients with SDS compared with healthy controls. Correlation analysis revealed that the increased FC between LFPN and DAN was positively correlated with 4-digitnumber reaction time mean (RTM) and 3-digitnumber RTM. CONCLUSION: Our study may provide novel insights into the relationship among the DMN, DAN, and FPN in NOGD patients with SDS to deepen our understanding of the neuropsychological mechanisms of SDS.

Shi-Zhen-An-Shen Decoction, a Herbal Medicine That Reverses Cuprizone-Induced Demyelination and Behavioral Deficits in Mice Independent of the Neuregulin-1 Pathway.

Shi-Zhen-An-Shen decoction (SZASD), a Chinese herbal medicine that is a liquor extracted from plants by boiling, has been reported to be effective in treating schizophrenia. However, the mechanism is unclear. Abnormal demyelination has been implicated in schizophrenia. The aim of this study was to investigate the effect of SZASD on myelin in demyelinated mice exhibiting schizophrenia-like behaviors. Sixty male C57BL/6 mice were randomly divided into six groups (n = 10 per group): (1) control group, (2) cuprizone (CPZ, a copper chelator that induced demyelination, 0.2% w/w)+saline, (3) CPZ+low-dose SZASD (8.65 g·kg-1·d-1), (4) CPZ+medium-dose SZASD (17.29 g·kg-1·d-1), (5) CPZ+high-dose SZASD (25.94 g·kg-1·d-1), and (6) CPZ+quetiapine (QTP, an atypical antipsychotic that served as a positive treatment control, 10 mg·kg-1·d-1). Mice in groups 2-6 were treated with CPZ added to rodent chow for six weeks to induce demyelination. During the last two weeks, these mice were given an oral gavage of sterile saline, SZASD, or quetiapine. Behavioral tests and brain analyses were conducted after the last treatment. The brain expression of myelin basic protein (MBP) and neuregulin-1 (NRG-1) was assessed using immunohistochemistry and Western blots. CPZ induced significant schizophrenia-like behaviors in the mice, including reduced nest-building activity and sensory gating deficits. Hyperlocomotor activity was accompanied by significant reductions in MBP expression in the corpus callosum, hippocampus, and cerebral cortex. However, both QTP and SZASD significantly reversed the schizophrenia-like behaviors and demyelination in CPZ-fed mice. The QTP and medium-dose SZASD resulted in better therapeutic effects compared to the low and high SZASD doses. Reduced NRG-1 expression was observed in CPZ-fed mice compared with controls, but neither QTP nor SZASD showed significant influence on NRG-1 expression in the hippocampus. Together, SZASD showed a therapeutic effect on demyelinated mice, and the improvement of demyelination might not be through the NRG-1 pathway.

Potential Locations for Non-Invasive Brain Stimulation in Treating Schizophrenia: A Resting-State Functional Connectivity Analysis.

Introduction: Non-invasive brain stimulation (NIBS) techniques have been widely used for the purpose of improving clinical symptoms of schizophrenia. However, the ambiguous stimulation targets may limit the efficacy of NIBS for schizophrenia. Exploring effective stimulation targets may improve the clinical efficacy of NIBS in schizophrenia. Methods: We first conducted a neurosynth-based meta-analysis of 715 functional magnetic resonance imaging studies to identify schizophrenia-related brain regions as regions of interest. Then, we performed the resting-state functional connectivity analysis in 32 patients with first-episode schizophrenia to find brain surface regions correlated with the regions of interest in three pipelines. Finally, the 10-20 system coordinates corresponding to the brain surface regions were considered as potential targets for NIBS. Results: We identified several potential targets of NIBS, including the bilateral dorsal lateral prefrontal cortex, supplementary motor area, bilateral inferior parietal lobule, temporal pole, medial prefrontal cortex, precuneus, superior and middle temporal gyrus, and superior and middle occipital gyrus. Notably, the 10-20 system location of the bilateral dorsal lateral prefrontal cortex was posterior to F3 (F4), not F3 (F4). Conclusion: Conclusively, our findings suggested that the stimulation locations corresponding to these potential targets might help clinicians optimize the application of NIBS therapy in individuals with schizophrenia.