Hyperactivity and altered functional connectivity of the ventral striatum in schizophrenia compared with bipolar disorder: A resting state fMRI study.

BACKGROUND: Schizophrenia patients frequently present with structural and functional abnormalities of the ventral striatum (VS). METHODS: we examined basal activation state and functional connectivity (FC) in four subregions of the bilateral ventral striatum: left inferior ventral striatum (VSi_L), left superior ventral striatum(VSs_L), right inferior ventral striatum(VSi_R), and right superior ventral striatum(VSs_R). Resting-state functional magnetic resonance images were obtained from 62 schizophrenia patients (SCH), 57 bipolar disorder (BD) patients, and 26 healthy controls (HCs). RESULTS: The schizophrenia group exhibited greater fALFF in bilateral VS subregions compared to BD and HC groups as well as greater FC between the bilateral VSi and multiple brain regions, including the thalamus, putamen, posterior cingulate gyrus (PCC), frontal cortex and caudate. Moreover, the fALFF values of the bilateral ventral striatum were positively correlated with the severity of positive symptoms. We also found the functional connectivity between the bilateral inferior ventral striatum and some brain regions aforementioned were positively correlated with the severity of negative symptoms. CONCLUSION: These findings confirm a crucial contribution of ventral striatum dysfunction, especially of the bilateral VSi in schizophrenia. Functionally dissociated regions of the ventral striatum are differentially disturbed in schizophrenia.

Trajectory of associative memory impairment during electroconvulsive therapy in depression.

Memory impairment is a serious cognitive side effect of electroconvulsive therapy (ECT) in the treatment of major depressive episodes (MDEs) and has garnered widespread attention in clinical practice, but its underlying evolution pattern during the course of ECT remains rarely understood in detail. Associative memory (AM) is a core indicator that reflects memory impairment in ECT. This study aimed to identify the dynamic trajectory of AM impairment and explore associated predictive factors. 405 intensive longitudinal AM data from 81 patients with MDE were collected at the baseline, after the first, third, fifth, and eighth ECT using five sets of face-cued word memory paradigms. Changes in AM score over time were analyzed using a linear mixed effects model. Trajectory subgroups and predictive factors were investigated using growth mixture model and logistic regression. AM score during ECT were significantly lower than at baseline, with the lowest scores observed after the eighth ECT session. Two trajectories of rapid (N = 56, 69.14%) and slow (N = 25, 30.86%) AM impairment were differentiated. Older female with lower education level were significant predictors contributing to more rapid memory impairment for ECT. The evolving pattern of associative memory impairment during ECT appears to occur early and worsen with subsequent treatment. This study may provide the important evidence understanding of the number effect of ECT sessions on memory impairment and suggest individual factors for predicting ECT memory outcome.

Abnormal large-scale resting-state functional networks in anti-N-methyl-D-aspartate receptor encephalitis.

Background: Patients with anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis often experience severe symptoms. Resting-state functional MRI (rs-fMRI) has revealed widespread impairment of functional networks in patients. However, the changes in information flow remain unclear. This study aims to investigate the intrinsic functional connectivity (FC) both within and between resting-state networks (RSNs), as well as the alterations in effective connectivity (EC) between these networks. Methods: Resting-state functional MRI (rs-fMRI) data were collected from 25 patients with anti-NMDAR encephalitis and 30 healthy controls (HCs) matched for age, sex, and educational level. Changes in the intrinsic functional connectivity (FC) within and between RSNs were analyzed using independent component analysis (ICA). The functional interaction between RSNs was identified by granger causality analysis (GCA). Results: Compared to HCs, patients with anti-NMDAR encephalitis exhibited lower performance on the Wisconsin Card Sorting Test (WCST), both in terms of correct numbers and correct categories. Additionally, these patients demonstrated decreased scores on the Montreal Cognitive Assessment (MoCA). Neuroimaging studies revealed abnormal intra-FC within the default mode network (DMN), increased intra-FC within the visual network (VN) and dorsal attention network (DAN), as well as increased inter-FC between VN and the frontoparietal network (FPN). Furthermore, aberrant effective connectivity (EC) was observed among the DMN, DAN, FPN, VN, and somatomotor network (SMN). Conclusion: Patients with anti-NMDAR encephalitis displayed noticeable deficits in both memory and executive function. Notably, these patients exhibited widespread impairments in intra-FC, inter-FC, and EC. These results may help to explain the pathophysiological mechanism of anti-NMDAR encephalitis.

Association between non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio (NHHR) and the risk of post-stroke depression: A cross-sectional study.

BACKGROUND: Limited observational research has explored the relationship between the non-high-density lipoprotein cholesterol (non-HDL-C) to high-density lipoprotein cholesterol (HDL-C) ratio (NHHR) and the risk of post-stroke depression (PSD). This study aims to investigate the potential associations between NHHR and PSD. METHODS: A cross-sectional study was conducted using data from stroke participants aged 20 and older, sourced from the National Health and Nutrition Examination Survey (NHANES) spanning 2005 to 2018. Depression was assessed using the PHQ-9 questionnaire. The association between NHHR and PSD risk was evaluated through weighted multivariate logistic regression and restricted cubic spline (RCS) models. Subgroup and sensitivity analyses were performed to validate the findings. RESULTS: In the continuous model, the NHHR value for the PSD group (3.23±1.84) was significantly higher than that of the non-PSD group (2.79±1.40, p=0.015). Logistic regression analysis in the fully adjusted model revealed a positive association between NHHR and PSD (OR 1.16, 95 % CI 1.03-1.30, p=0.016). Interaction tests showed no significant differences across strata (p > 0.05 for interaction). Restricted cubic spline results indicated a linear dose-response relationship between NHHR and PSD risk (P for non-linearity = 0.6). This association persisted in various subgroup analyses. CONCLUSION: NHHR was significantly correlated with an increased risk of PSD among U.S. adults. Further re-search on NHHR could contribute to the prevention and treatment of PSD.

The shared genetic etiology of antisocial behavior and psychiatric disorders: Insights from pleiotropy and causality analysis.

BACKGROUND: Antisocial behavior (ASB) infringes on the rights of others and significantly disrupts social order. Studies have shown that ASB is phenotypically associated with various psychiatric disorders. However, these studies often neglected the importance of genetic foundations. METHODS: This study utilized genome-wide association studies and pleiotropy analysis to explore the genetic correlation between ASB and psychiatric disorders. Linkage disequilibrium score regression (LDSC) and high-definition likelihood (HDL) methods were employed to assess genetic correlations, and the PLACO method was used for pleiotropy analysis. Functional annotation and biological pathway analysis of identified pleiotropic genes were performed using enrichment analysis. Furthermore, Mendelian randomization (MR) analysis was conducted to validate these causal relationships. RESULTS: LDSC and HDL analysis showed that significant positive genetic correlations were between ASB and attention deficit hyperactivity disorder (ADHD), schizophrenia (SCZ), major depressive disorder (MDD), and post-traumatic stress disorder (PTSD). Multiple potential pleiotropic genetic loci were identified, particularly the FOXP2 and MDFIC genes located at the 7q31.1 locus. Enrichment analysis showed that these pleiotropic genes are highly expressed in several brain regions (such as the hypothalamus, cerebellar hemisphere, cortex, and amygdala) and immune-related cells. MR analysis further confirmed the causal effects ADHD, SCZ, and MDD on ASB risk. CONCLUSION: This study reveals significant genetic correlations and potential causal mechanisms between ASB and various psychiatric disorders. The MR analysis confirmed the causal effects of psychiatric disorders on ASB. These findings deepen our understanding of the genetic architecture of psychiatric disorders and ASB.

Genetically proxied appendicular lean mass and stroke risk: A two-step mendelian randomization study.

BACKGROUND AND PURPOSE: Prior observational studies have suggested a strong correlation between sarcopenia and stroke, but the causal link between them remains uncertain. This study aims to investigate the associations between genetically predicted sarcopenia-related traits and stroke using a two-step Mendelian randomization (MR) approach. METHODS: Genome-wide association study (GWAS) summary data for sarcopenia-related traits were acquired from the UK Biobank. Genetic associations for ischemic stroke (IS) and its subtypes were selected from the MEGASTROKE consortium comprising European ancestry participants. GWAS summary data for cerebral hemorrhage were obtained from the FinnGen consortium, including intracerebral hemorrhage (ICH) and subarachnoid hemorrhage (SAH). MR estimates were calculated using the inverse-variance weighted (IVW) method. The robustness of results was assessed for heterogeneity and pleiotropy of individual single nucleotide polymorphisms (SNPs). RESULTS: Higher appendicular lean mass (ALM) exhibited a potential causal association with a reduced incidence of large artery atherosclerosis (LAA) (odds ratio [OR] = 0.81, 95% confidence interval [CI]:0.71-0.93; P = 0.003) and small vessel disease (SVD) (OR = 0.83, 95% CI:0.74-0.94; P = 0.002). The associations of ALM with IS and ICH were compromised after adjusting for body fat and physical activity with multivariable MR. Two-step MR mediation analysis explored 33 candidate mediators, among which hypertension and SBP accounted for more than 10% of the mediation proportion in the relationship between ALM and stroke and its subtypes. CONCLUSION: Our research findings indicate that lower ALM is associated with a increased risk of stroke . It is necessary to explore the specific protective mechanisms of higher ALM for preventing stroke occurrence.

The Montreal cognitive assessment: normative data from a large, population-based sample of Chinese healthy adults and validation for detecting vascular cognitive impairment.

Background: The Montreal Cognitive Assessment (MoCA) is a valuable tool for detecting cognitive impairment, widely used in many countries. However, there is still a lack of large sample normative data and whose cut-off values for detecting cognitive impairment is considerable controversy. Methods: The assessment conducted in this study utilizes the MoCA scale, specifically employing the Mandarin-8.1 version. This study recruited a total of 3,097 healthy adults aged over 20 years. We performed multiple linear regression analysis, incorporating age, gender, and education level as predictor variables, to examine their associations with the MoCA total score and subdomain scores. Subsequently, we established normative values stratified by age and education level. Finally, we included 242 patients with vascular cognitive impairment (VCI) and 137 controls with normal cognition, and determined the optimal cut-off value of VCI through ROC curves. Results: The participants in this study exhibit a balanced gender distribution, with an average age of 54.46 years (SD = 14.38) and an average education period of 9.49 years (SD = 4.61). The study population demonstrates an average MoCA score of 23.25 points (SD = 4.82). The multiple linear regression analysis indicates that MoCA total score is influenced by age and education level, collectively accounting for 46.8% of the total variance. Higher age and lower education level are correlated with lower MoCA total scores. A score of 22 is the optimal cut-off value for diagnosing vascular cognitive impairment (VCI). Conclusion: This study offered normative MoCA values specific to the Chinese adults. Furthermore, this study indicated that a score of 26 may not represent the most optimal cut-off value for VCI. And for detecting VCI, a score of 22 may be a better cut-off value.

Non-invasive brain stimulation in the treatment of generalized anxiety disorder: A systematic review and meta-analysis.

BACKGROUND: Non-invasive brain stimulation (NIBS), including repetitive transcranial magnetic stimulation (rTMS), continuous theta-burst stimulation (cTBS), and transcranial direct current stimulation (tDCS), is an emerging intervention that has been used to treat various mental illnesses. However, previous studies have not comprehensively compared the efficacies of various NIBS modalities in alleviating anxiety symptoms among patients with generalized anxiety disorder (GAD). Therefore, this study conducted a systematic review and meta-analysis to assess the efficacy of NIBS for patients with GAD. METHODS: A systematic search of four major bibliographic databases (Embase, PubMed, Web of Science and The Cochrane Library) was conducted from inception dates to November 26, 2023 to identify eligible studies. The data were analyzed using a random-effects model. RESULTS: Seven randomized controlled trials (RCTs) were included in the meta-analysis. Significant differences were found in changes in Hamilton anxiety rating scale (HARS) scores, study-defined response, and remission between the intervention and control groups. Moreover, the intervention groups experienced a significantly higher frequency of headaches. CONCLUSION: The results revealed that interventions improved GAD compared to control groups. cTBS and rTMS exhibited better treatment efficacy than tDCS, which did not appear to have a significant therapeutic effect. Longer follow-up periods and larger sample sizes are required in future RCTs. TRIAL REGISTRATION: This meta-analysis was conducted in accordance with PRISMA guidelines and registered at PROSPERO (https://www.crd.york.ac.uk/PROSPERO/, CRD42023466285).

Alterations in neural circuit dynamics between the limbic network and prefrontal/default mode network in patients with generalized anxiety disorder.

BACKGROUND: Widespread functional alterations have been implicated in patients with generalized anxiety disorder (GAD). However, most studies have primarily focused on static brain network features in patients with GAD. The current research focused on exploring the dynamics within functional brain networks among individuals diagnosed with GAD. METHODS: Seventy-five participants were divided into patients with GAD and healthy controls (HCs), and resting-state functional magnetic resonance imaging data were collected. The severity of symptoms was measured using the Hamilton Anxiety Scale and the Patient Health Questionnaire. Co-activation pattern (CAP) analysis, centered on the bed nucleus of the stria terminalis, was applied to explore network dynamics. The capability of these dynamic characteristics to distinguish between patients with GAD and HCs was evaluated using a support vector machine. RESULTS: Patients with GAD exhibited disruptions in the limbic-prefrontal and limbic-default-mode network circuits. Particularly noteworthy was the marked reduction in dynamic indicators such as occurrence, EntriesFromBaseline, ExitsToBaseline, in-degree, out-degree, and resilience. Moreover, these decreased dynamic features effectively distinguished the GAD group from the HC in this study. CONCLUSIONS: The current findings revealed the underlying brain networks associated with compromised emotion regulation in individuals with GAD. The dynamic reduction in connectivity between the limbic-default mode network and limbic-prefrontal networks could potentially act as a biomarker and therapeutic target for GAD in the future.

Inhibiting the JNK Signaling Pathway Attenuates Hypersensitivity and Anxiety-Like Behavior in a Rat Model of Non-specific Chronic Low Back Pain.

Low back pain (LBP) has become a leading cause of disability worldwide. Astrocyte activation in the spinal cord plays an important role in the maintenance of latent sensitization of dorsal horn neurons in LBP. However, the role of spinal c-Jun N-terminal kinase (JNK) in astrocytes in modulating pain behavior of LBP model rats and its neurobiological mechanism have not been elucidated. Here, we investigate the role of the JNK signaling pathway on hypersensitivity and anxiety-like behavior caused by repetitive nerve growth factor (NGF) injections in male non-specific LBP model rats. LBP was produced by two injections (day 0, day 5) of NGF into multifidus muscle of the low backs of rats. We observed prolonged mechanical and thermal hypersensitivity in the low backs or hindpaws. Persistent anxiety-like behavior was observed, together with astrocyte, p-JNK, and neuronal activation and upregulated expression of monocyte chemoattractant protein-1 (MCP-1), and chemokine (C-X-C motif) ligand 1 (CXCL1) proteins in the spinal L2 segment. Second, the JNK inhibitor SP600125 was intrathecally administrated in rats from day 10 to day 12. It attenuated mechanical and thermal hypersensitivity of the low back or hindpaws and anxiety-like behavior. Meanwhile, SP600125 decreased astrocyte and neuronal activation and the expression of MCP-1 and CXCL1 proteins. These results showed that hypersensitivity and anxiety-like behavior induced by NGF in LBP rats could be attenuated by the JNK inhibitor, together with downregulation of spinal astrocyte activation, neuron activation, and inflammatory cytokines. Our results indicate that intervening with the spinal JNK signaling pathway presents an effective therapeutic approach to alleviating LBP.

Altered Resting-State Brain Entropy in Cerebral Small Vessel Disease Patients with Cognitive Impairment.

Objective: Cerebral small vessel disease (CSVD) is a primary vascular disease of cognitive impairment. Previous studies have predominantly focused on brain linear features. However, the nonlinear measure, brain entropy (BEN), has not been elaborated. Thus, this study aims to investigate if BEN abnormalities could manifest in CSVD patients with cognitive impairment. Methods: Thirty-four CSVD patients with cognitive impairment and 37 healthy controls (HCs) were recruited. Analysis of gray matter approximate entropy (ApEn) and sample entropy (SampEn) which are two indices of BEN was calculated. To explore whether BEN can provide unique information, we further performed brain linear methods, namely, amplitude of low frequency fluctuation (ALFF) and regional homogeneity (ReHo), to observe their differences. The ratios of BEN/ALFF and BEN/ReHo which represent the coupling of nonlinear and linear features were introduced. Correlation analysis was conducted between imaging indices and cognition. Subsequently, the linear support vector machine (SVM) was used to assess their discriminative ability. Results: CSVD patients exhibited lower ApEn and SamEn values in sensorimotor areas, which were correlated with worse memory and executive function. In addition, the results of BEN showed little overlap with ALFF and ReHo in brain regions. Correlation analysis also revealed a relationship between the two ratios and cognition. SVM analysis using BEN and its ratios as features achieved an accuracy of 74.64% (sensitivity: 86.49%, specificity: 61.76%, and AUC: 0.82439). Conclusion: Our study reveals that the reduction of sensorimotor system complexity is correlated with cognition. BEN exhibits distinctive characteristics in brain activity. Combining BEN and the ratios can be new biomarkers to diagnose CSVD with cognitive impairment.

The association between lipid accumulation products and depression in U.S. adults: A cross-sectional study from NHANES 2005-2018.

OBJECTIVE: To investigate the potential correlation between lipid accumulation products (LAP) and depression in adults in the United States. METHODS: We analyzed data from 13,051 participants from the NHANES 2005-2018 cycle. The LAP index was calculated using the waist circumference (WC) and serum triglyceride (TG) levels, which reflect lipid toxicity. Participants who scored ≥10 on the patient health questionnaire-9 (PHQ-9) were considered depressed. Multivariate logistic regression analyses were conducted to explore the association between the LAP index and depression. Furthermore, we conducted subgroup analysis to identify potentially sensitive populations. Smoothed curve fitting and generalized additive model (GAM) regression were performed to verify the association between the LAP index and depression. RESULTS: A total of 13,051 participants were eligible for analysis. After adjusting for all potential confounders, the risk of depression tended to increase with an increasing LAP index (odds ratio [OR]: 1.0011, 95% confidence interval [CI]: 1.0001, 1.0021). Compared to participants with LAP quartile 1, participants with LAP quartile 3 exhibited the highest risk of depression (OR: 1.43, 95%CI: 1.03, 1.99). Subgroup analysis demonstrated a strong association between the LAP index and depression in men (OR: 1.002, 95%CI: 1.001, 1.004) or those with hypertension (OR: 1.002, 95%CI: 1.000, 1.003). Additionally, smoothed curve fitting and GAM regression demonstrated a positive linear correlation between the LAP index and depression. CONCLUSIONS: Our findings suggest that individuals with a higher LAP index may be at higher risk of depression, particularly men or those with hypertension. However, further studies are required to confirm these findings.

Brain functional specialization and cooperation in Alzheimer's disease.

BACKGROUND: Cerebral specialization and interhemispheric cooperation are two vital features of the human brain. Their dysfunction may be associated with disease progression in patients with Alzheimer's disease (AD), which is featured as progressive cognitive degeneration and asymmetric neuropathology. OBJECTIVE: This study aimed to examine and define two inherent properties of hemispheric function in patients with AD by utilizing resting-state functional magnetic resonance imaging (rs-fMRI). METHODS: Sixty-four clinically diagnosed AD patients and 52 age- and sex-matched cognitively normal subjects were recruited and underwent MRI and clinical evaluation. We calculated and compared brain specialization (autonomy index, AI) and interhemispheric cooperation (connectivity between functionally homotopic voxels, CFH). RESULTS: In comparison to healthy controls, patients with AD exhibited enhanced AI in the left middle occipital gyrus. This increase in specialization can be attributed to reduced functional connectivity in the contralateral region, such as the right temporal lobe. The CFH of the bilateral precuneus and prefrontal areas was significantly decreased in AD patients compared to controls. Imaging-cognitive correlation analysis indicated that the CFH of the right prefrontal cortex was marginally positively related to the Montreal Cognitive Assessment score in patients and the Auditory Verbal Learning Test score. Moreover, taking abnormal AI and CFH values as features, support vector machine-based classification achieved good accuracy, sensitivity, specificity, and area under the curve by leave-one-out cross-validation. CONCLUSION: This study suggests that individuals with AD have abnormal cerebral specialization and interhemispheric cooperation. This provides new insights for further elucidation of the pathological mechanisms of AD.

Decreased inter-hemispheric cooperation in major depressive disorder and its association with neurotransmitter profiles.

BACKGROUND: Inter-hemispheric cooperation is a prominent feature of the human brain, and previous neuroimaging studies have revealed aberrant inter-hemispheric cooperation patterns in patients with major depressive disorder (MDD). Typically, inter-hemispheric cooperation is examined by calculating the functional connectivity (FC) between each voxel in one hemisphere and its anatomical (structurally homotopic) counterpart in the opposite hemisphere. However, bilateral hemispheres are actually asymmetric in anatomy. METHODS: In the present study, we utilized connectivity between functionally homotopic voxels (CFH) to investigate abnormal inter-hemispheric cooperation in 96 MDD patients compared to 173 age- and sex-matched healthy controls (HCs). In addition, we analyzed the spatial correlations between abnormal CFH and the density maps of 13 neurotransmitter receptors and transporters. RESULTS: The CFH values in bilateral orbital frontal gyri and bilateral postcentral gyri were abnormally decreased in patients with MDD. Furthermore, these CFH abnormalities were correlated with clinical symptoms. In addition, the abnormal CFH pattern in MDD patients was spatially correlated with the distribution pattern of 5-HT1AR. LIMITATIONS: drug effect; the cross-sectional research design precludes causal inferences; the neurotransmitter atlases selected were constructed from healthy individuals rather than MDD patients. CONCLUSION: These findings characterized the abnormal inter-hemispheric cooperation in MDD using a novel method and the underlying neurotransmitter mechanism, which promotes our understanding of the pathophysiology of depression.

Reviving Bistable Perception in Patients With Depression by Decreasing the Overestimation of Prior Precision.

Slower perceptual alternations, a notable perceptual effect observed in psychiatric disorders, can be alleviated by antidepressant therapies that affect serotonin levels in the brain. While these phenomena have been well documented, the underlying neurocognitive mechanisms remain to be elucidated. Our study bridges this gap by employing a computational cognitive approach within a Bayesian predictive coding framework to explore these mechanisms in depression. We fitted a prediction error (PE) model to behavioral data from a binocular rivalry task, uncovering that significantly higher initial prior precision and lower PE led to a slower switch rate in patients with depression. Furthermore, serotonin-targeting antidepressant treatments significantly decreased the prior precision and increased PE, both of which were predictive of improvements in the perceptual alternation rate of depression patients. These findings indicated that the substantially slower perception switch rate in patients with depression was caused by the greater reliance on top-down priors and that serotonin treatment's efficacy was in its recalibration of these priors and enhancement of PE. Our study not only elucidates the cognitive underpinnings of depression, but also suggests computational modeling as a potent tool for integrating cognitive science with clinical psychology, advancing our understanding and treatment of cognitive impairments in depression.

A Study on the Effect of Executive Control Network Functional Connection on the Therapeutic Efficacy of Repetitive Transcranial Magnetic Stimulation in Alzheimer's Disease.

Background: Alzheimer's disease (AD) is a neurodegenerative disease characterized by brain network dysfunction. Few studies have investigated whether the functional connections between executive control networks (ECN) and other brain regions can predict the therapeutic effect of repetitive transcranial magnetic stimulation (rTMS). Objective: The purpose of this study is to examine the relationship between the functional connectivity (FC) within ECN networks and the efficacy of rTMS. Methods: We recruited AD patients for rTMS treatment. We established an ECN using baseline period fMRI data and conducted an analysis of the ECN's FC throughout the brain. Concurrently, the support vector regression (SVR) method was employed to project post-rTMS cognitive scores, utilizing the connectional attributes of the ECN as predictive markers. Results: The average age of the patients was 66.86±8.44 years, with 8 males and 13 females. Significant improvement on most cognitive measures. We use ECN connectivity and brain region functions in baseline patients as features for SVR model training and fitting. The SVR model could demonstrate significant predictability for changes in Montreal Cognitive Assessment scores among AD patients after rTMS treatment. The brain regions that contributed most to the prediction of the model (the top 10% of weights) were located in the medial temporal lobe, middle temporal gyrus, frontal lobe, parietal lobe and occipital lobe. Conclusions: The stronger the antagonism between ECN and parieto-occipital lobe function, the better the prediction of cognitive improvement; the stronger the synergy between ECN and fronto-temporal lobe function, the better the prediction of cognitive improvement.

Individual large-scale functional network mapping for major depressive disorder with electroconvulsive therapy.

Personalized functional connectivity mapping has been demonstrated to be promising in identifying underlying neurophysiological basis for brain disorders and treatment effects. Electroconvulsive therapy (ECT) has been proved to be an effective treatment for major depressive disorder (MDD) while its active mechanisms remain unclear. Here, 46 MDD patients before and after ECT as well as 46 demographically matched healthy controls (HC) underwent resting-state functional magnetic resonance imaging (rs-fMRI) scans. A spatially regularized form of non-negative matrix factorization (NMF) was used to accurately identify functional networks (FNs) in individuals to map individual-level static and dynamic functional network connectivity (FNC) to reveal the underlying neurophysiological basis of therepetical effects of ECT for MDD. Moreover, these static and dynamic FNCs were used as features to predict the clinical treatment outcomes for MDD patients. We found that ECT could modulate both static and dynamic large-scale FNCs at individual level in MDD patients, and dynamic FNCs were closely associated with depression and anxiety symptoms. Importantly, we found that individual FNCs, particularly the individual dynamic FNCs could better predict the treatment outcomes of ECT suggesting that dynamic functional connectivity analysis may be better to link brain functional characteristics with clinical symptoms and treatment outcomes. Taken together, our findings provide new evidence for the active mechanisms and biomarkers for ECT to improve diagnostic accuracy and to guide individual treatment selection for MDD patients.

Molecular mechanisms underlying structural plasticity of electroconvulsive therapy in major depressive disorder.

Although previous studies reported structural changes associated with electroconvulsive therapy (ECT) in major depressive disorder (MDD), the underlying molecular basis of ECT remains largely unknown. Here, we combined two independent structural MRI datasets of MDD patients receiving ECT and transcriptomic gene expression data from Allen Human Brain Atlas to reveal the molecular basis of ECT for MDD. We performed partial least square regression to explore whether/how gray matter volume (GMV) alterations were associated with gene expression level. Functional enrichment analysis was conducted using Metascape to explore ontological pathways of the associated genes. Finally, these genes were further assigned to seven cell types to determine which cell types contribute most to the structural changes in MDD patients after ECT. We found significantly increased GMV in bilateral hippocampus in MDD patients after ECT. Transcriptome-neuroimaging association analyses showed that expression levels of 726 genes were positively correlated with the increased GMV in MDD after ECT. These genes were mainly involved in synaptic signaling, calcium ion binding and cell-cell signaling, and mostly belonged to excitatory and inhibitory neurons. Moreover, we found that the MDD risk genes of CNR1, HTR1A, MAOA, PDE1A, and SST as well as ECT related genes of BDNF, DRD2, APOE, P2RX7, and TBC1D14 showed significantly positive associations with increased GMV. Overall, our findings provide biological and molecular mechanisms underlying structural plasticity induced by ECT in MDD and the identified genes may facilitate future therapy for MDD.

Modulation of hemispheric asymmetry in executive control of attention in schizophrenia with atypical antipsychotic treatment: Potential benefits of olanzapine.

Deficits in executive control of attention have been reported in schizophrenia patients, but can be ameliorated by treatment of atypical antipsychotics along with the symptoms. However, it remains unclear whether this effect is related to a modulation of hemispheric asymmetry in executive control by the medicine. In this behavioral study, we employed a lateralized version of the attention network test to examine the hemispheric asymmetry of executive control in schizophrenia patients before and after olanzapine treatment, compared to matched healthy controls. Executive control was measured as a conflict effect, indexed as the response time (RT) difference between incongruent versus congruent flanker conditions, and was compared between stimuli presented in the left and the right visual field (i.e., processed by right versus left hemisphere of the brain). Results showed that pre-treatment schizophrenia patients revealed a right hemisphere superiority in conflict effect (i.e., a smaller effect in the right hemisphere than in the left hemisphere), driven by the incongruent condition. Olanzapine treatment reduced this right hemisphere superiority by improving the efficiency of the left hemisphere in the incongruent condition. These results suggested that olanzapine treatment may improve the efficiency of executive control in the left hemisphere in schizophrenia patients.

Molecular basis underlying changes of brain entropy and functional connectivity in major depressive disorders after electroconvulsive therapy.

INTRODUCTION: Electroconvulsive therapy (ECT) is widely used for treatment-resistant depression. However, it is unclear whether/how ECT can be targeted to affect brain regions and circuits in the brain to dynamically regulate mood and cognition. METHODS: This study used brain entropy (BEN) to measure the irregular levels of brain systems in 46 major depressive disorder (MDD) patients before and after ECT treatment. Functional connectivity (FC) was further adopted to reveal changes of functional couplings. Moreover, transcriptomic and neurotransmitter receptor data were used to reveal genetic and molecular basis of the changes of BEN and functional connectivities. RESULTS: Compared to pretreatment, the BEN in the posterior cerebellar lobe (PCL) significantly decreased and FC between the PCL and the right temporal pole (TP) significantly increased in MDD patients after treatment. Moreover, we found that these changes of BEN and FC were closely associated with genes' expression profiles involved in MAPK signaling pathway, GABAergic synapse, and dopaminergic synapse and were significantly correlated with the receptor/transporter density of 5-HT, norepinephrine, glutamate, etc. CONCLUSION: These findings suggest that loops in the cerebellum and TP are crucial for ECT regulation of mood and cognition, which provides new evidence for the antidepressant effects of ECT and the potential molecular mechanism leading to cognitive impairment.