Altered effective connectivity of the default mode network in juvenile myoclonic epilepsy.

Juvenile myoclonic epilepsy (JME) is associated with brain dysconnectivity in the default mode network (DMN). Most previous studies of patients with JME have assessed static functional connectivity in terms of the temporal correlation of signal intensity among different brain regions. However, more recent studies have shown that the directionality of brain information flow has a more significant regional impact on patients' brains than previously assumed in the present study. Here, we introduced an empirical approach incorporating independent component analysis (ICA) and spectral dynamic causal modeling (spDCM) analysis to study the variation in effective connectivity in DMN in JME patients. We began by collecting resting-state functional magnetic resonance imaging (rs-fMRI) data from 37 patients and 37 matched controls. Then, we selected 8 key nodes within the DMN using ICA; finally, the key nodes were analyzed for effective connectivity using spDCM to explore the information flow and detect patient abnormalities. This study found that compared with normal subjects, patients with JME showed significant changes in the effective connectivity among the precuneus, hippocampus, and lingual gyrus (p < 0.05 with false discovery rate (FDR) correction) with most of the effective connections being strengthened. In addition, previous studies have found that the self-connection of normal subjects' nodes showed strong inhibition, but the self-connection inhibition of the anterior cingulate cortex and lingual gyrus of the patient was decreased in this experiment (p < 0.05 with FDR correction); as the activity in these areas decreased, the nodes connected to them all appeared abnormal. We believe that the changes in the effective connectivity of nodes within the DMN are accompanied by changes in information transmission that lead to changes in brain function and impaired cognitive and executive function in patients with JME. Overall, our findings extended the dysconnectivity hypothesis in JME from static to dynamic causal and demonstrated that aberrant effective connectivity may underlie abnormal brain function in JME patients at early phase of illness, contributing to the understanding of the pathogenesis of JME. Supplementary Information: The online version contains supplementary material available at 10.1007/s11571-023-09994-4.

Effects of escitalopram therapy on effective connectivity among core brain networks in major depressive disorder.

BACKGROUND: Patients with major depressive disorder (MDD) have abnormal functional interaction among large-scale brain networks, indicated by aberrant effective connectivity of the default mode network (DMN), salience network (SN), and dorsal attention network (DAN). However, it remains unclear whether antidepressants can normalize the altered effective connectivity in MDD. METHODS: In this study, we collected resting-state functional magnetic resonance imaging data from 46 unmedicated patients with MDD at baseline and after 12 weeks of escitalopram treatment. We also collected data from 58 healthy controls (HCs) at the same time point with the same interval. Using spectral dynamic causal modeling and parametric empirical Bayes, we examined group differences, time effect and their interaction on the casual interactions among the regions of interest in the three networks. RESULTS: Compared with HCs, patients with MDD showed increased positive (excitatory) connections within the DMN, decreased positive connections within the SN and DAN, decreased absolute value of negative (inhibitory) connectivity from the SN and DAN to the DMN, and decreased positive connections between the DAN and the SN. Furthermore, we found that six connections related to the DAN showed decreased group differences in effective connectivity between MDD and HCs during follow-up compared to the baseline. CONCLUSIONS: Our findings suggest that escitalopram therapy can partly improve the disrupted effective connectivity among high-order brain functional networks in MDD. These findings deepened our understanding of the neural basis of antidepressants' effect on brain function in patients with MDD.

Altered effective connectivity from cerebellum to motor cortex in chronic low back pain: A multivariate pattern analysis and spectral dynamic causal modeling study.

To explore the central processing mechanism of pain perception in chronic low back pain (cLBP) using multi-voxel pattern analysis (MVPA) based on the static and dynamic fractional amplitude of low-frequency fluctuations (fALFF) analysis, and spectral dynamic causal modeling (spDCM). Thirty-two patients with cLBP and 29 matched healthy controls (HCs) for the first cohort and 24 patients with cLBP and 22 HCs for the validation cohort underwent resting-state fMRI scan. The alterations in static and dynamic fALFF were as classification features to distinguish patients with cLBP from HCs. The brain regions gotten from the MVPA results were used for further spDCM analysis. We found that the most discriminative brain regions that contributed to the classification were the right supplementary motor area (SMA.R), left paracentral lobule (PCL.L), and bilateral cerebellar Crus II. The spDCM results displayed decreased excitatory influence from the bilateral cerebellar Crus II to PCL.L in patients with cLBP compared with HCs. Moreover, the conversion of effective connectivity from the bilateral cerebellar Crus II to SMA.R from excitatory influence to inhibitive influence, and the effective connectivity strength exhibited partially mediated effects on Chinese Short Form Oswestry Disability Index Questionnaire (C-SFODI) scores. Our findings suggest that the cerebellum and its weakened or inhibited connections to the motor cortex may be one of the underlying feedback pathways for pain perception in cLBP, and partially mediate the degree of dysfunction.

Altered effective connectivity between reward and inhibitory control networks in people with binge eating episodes: A spectral dynamic causal modeling study.

BACKGROUND: Converging evidence points to the crucial role of brain connectivity involved in aberrant behavioral control and reward reactivity in the onset and maintenance of binge eating. However, the directional interaction pattern between brain's reward and inhibitory control systems in people with binge eating episodes is largely unknown. METHODS: Resting-state fMRI data were collected from 36 adults with binge eating episodes (age: 19.05 ± 0.90) and 36 well-matched controls (age: 18.88 ± 0.78). We applied spectral dynamic causal modeling approach to estimate effective connectivity of the executive control network (ECN) and reward network (RN) with 15 predefined regions of interest, and investigate the between-group differences in directional connectivity. RESULTS: Compared with controls, the positive connections within the ECN were significantly strengthened in individuals with binge eating episodes, while the negative connections from the ECN to RN and from the RN to ECN were significantly weakened. In adults with binge eating episodes, the RN→ECN connectivity was positively related to binge frequency even controlling for age, sex, and body mass index. CONCLUSION: This study represents an important first step in addressing the role of directional integration between reward and inhibitory control networks in binge eating, and provides novel evidence that the ability of people with binge eating episodes to maintain a balance between inhibitory control and reward reactivity is decreased, as reflected by diminished bidirectional negative effects of prefrontal-subcortical circuitry at rest.

Effective Connectivity Evaluation of Resting-State Brain Networks in Alzheimer's Disease, Amnestic Mild Cognitive Impairment, and Normal Aging: An Exploratory Study.

(1) Background: Alzheimer's disease (AD) is a neurodegenerative disease with a high prevalence. Despite the cognitive tests to diagnose AD, there are pitfalls in early diagnosis. Brain deposition of pathological markers of AD can affect the direction and intensity of the signaling. The study of effective connectivity allows the evaluation of intensity flow and signaling pathways in functional regions, even in the early stage, known as amnestic mild cognitive impairment (aMCI). (2) Methods: 16 aMCI, 13 AD, and 14 normal subjects were scanned using resting-state fMRI and T1-weighted protocols. After data pre-processing, the signal of the predefined nodes was extracted, and spectral dynamic causal modeling analysis (spDCM) was constructed. Afterward, the mean and standard deviation of the Jacobin matrix of each subject describing effective connectivity was calculated and compared. (3) Results: The maps of effective connectivity in the brain networks of the three groups were different, and the direction and strength of the causal effect with the progression of the disease showed substantial changes. (4) Conclusions: Impaired information flow in the resting-state networks of the aMCI and AD groups was found versus normal groups. Effective connectivity can serve as a potential marker of Alzheimer's pathophysiology, even in the early stages of the disease.

Effective Connectivity Between the Orbitofrontal Cortex and the Precuneus Differentiates Major Psychiatric Disorders: Results from a Transdiagnostic Spectral DCM Study.

BACKGROUND & OBJECTIVE: We have previously identified aberrant connectivity of the left precuneus, ventrolateral prefrontal cortex, anterior cingulate cortex, and anterior insula in patients with either a paranoid (schizophrenia), or a depressive syndrome (both unipolar and bipolar). In the current study, we attempted to replicate and expand these findings by including a healthy control sample and separating the patients in a depressive episode into two groups: unipolar and bipolar depression. We hypothesized that the connections between those major nodes of the resting state networks would demonstrate different patterns in the three patient groups compared to the healthy subjects. METHODS: Resting-state functional MRI was performed on a sample of 101 participants, of which 26 patients with schizophrenia (current psychotic episodes), 24 subjects with Bipolar Disorder (BD), 33 with Major Depressive Disorder (MDD) (both BD and MDD patients were in a current depressive episode), and 21 healthy controls. Spectral Dynamic Causal Modeling was used to calculate the coupling values between eight regions of interest, including the anterior precuneus (PRC), anterior hippocampus, anterior insula, angular gyrus, lateral Orbitofrontal Cortex (OFC), middle frontal gyrus, planum temporale, and anterior thalamus. RESULTS & CONCLUSION: We identified disturbed effective connectivity from the left lateral orbitofrontal cortex to the left anterior precuneus that differed significantly between unipolar depression, where the influence was inhibitory, and bipolar depression, where the effect was excitatory. A logistic regression analysis correctly classified 75% of patients with unipolar and bipolar depression based solely on the coupling values of this connection. In addition, patients with schizophrenia demonstrated negative effective connectivity from the anterior PRC to the lateral OFC, which distinguished them from healthy controls and patients with major depression. Future studies with unmedicated patients will be needed to establish the replicability of our findings.

Intrinsic excitability of human right parietal cortex shapes the experienced visual size illusions.

Converging evidence has found that the perceived visual size illusions are heritable, raising the possibility that visual size illusions might be predicted by intrinsic brain activity without external stimuli. Here we measured resting-state brain activity and 2 classic visual size illusions (i.e. the Ebbinghaus and the Ponzo illusions) in succession, and conducted spectral dynamic causal modeling analysis among relevant cortical regions. Results revealed that forward connection from right V1 to superior parietal lobule (SPL) was predictive of the Ebbinghaus illusion, and self-connection in the right SPL predicted the Ponzo illusion. Moreover, disruption of intrinsic activity in the right SPL by repetitive transcranial magnetic stimulation (TMS) temporally increased the Ebbinghaus rather than the Ponzo illusion. These findings provide a better mechanistic understanding of visual size illusions by showing the causal and distinct contributions of right parietal cortex to them, and suggest that spontaneous fluctuations in intrinsic brain activity are relevant to individual difference in behavior.

Abnormal effective connectivity in visual cortices underlies stereopsis defects in amblyopia.

The neural basis underlying stereopsis defects in patients with amblyopia remains unclear, which hinders the development of clinical therapy. This study aimed to investigate visual network abnormalities in patients with amblyopia and their associations with stereopsis function. Spectral dynamic causal modeling methods were employed for resting-state functional magnetic resonance imaging data to investigate the effective connectivity (EC) among 14 predefined regions of interest in the dorsal and ventral visual pathways. We adopted two independent datasets, including a cross-sectional and a longitudinal dataset. In the cross-sectional dataset, we compared group differences in EC between 31 patients with amblyopia (mean age: 26.39 years old) and 31 healthy controls (mean age: 25.71 years old) and investigated the association between EC and stereoacuity. In addition, we explored EC changes after perceptual learning in a novel longitudinal dataset including 9 patients with amblyopia (mean age: 15.78 years old). We found consistent evidence from the two datasets indicating that the aberrant EC from V2v to LO2 is crucial for the stereoscopic deficits in the patients with amblyopia: it was weaker in the patients than in the controls, showed a positive linear relationship with the stereoscopic function, and increased after perceptual learning in the patients. In addition, higher-level dorsal (V3d, V3A, and V3B) and ventral areas (LO1 and LO2) were important nodes in the network of abnormal ECs associated with stereoscopic deficits in the patients with amblyopia. Our research provides insights into the neural mechanism underlying stereopsis deficits in patients with amblyopia and provides candidate targets for focused stimulus interventions to enhance the efficacy of clinical treatment for the improvement of stereopsis deficiency.

Altered dynamic interactions within frontostriatal circuits reflect disturbed craving processing in internet gaming disorder.

BACKGROUND: Individuals with internet gaming disorder (IGD) are generally characterized by impaired executive control, persistent game-craving, and excessive reward-seeking behaviors. However, the causal interactions within the frontostriatal circuits underlying these problematic behaviors remain unclear. Here, spectral dynamic causal modeling (spDCM) was implemented to explore this issue. METHODS: Resting-state functional magnetic resonance imaging data from 317 online game players (148 IGD subjects and 169 recreational game users (RGUs)) were collected. Using independent component analysis, we determined six region of interests within frontostriatal circuits for further spDCM analysis, and further statistical analyses based on the parametric empirical Bayes framework were performed. RESULTS: Compared with RGUs, IGD subjects showed inhibitory effective connectivity from the right orbitofrontal cortex (OFC) to the right caudate and from the right dorsolateral prefrontal cortex to the left OFC; at the same time, excitatory effective connectivity was observed from the thalamus to the left OFC. Correlation analyses results showed that the directional connection from the right OFC to the right caudate was negatively associated with addiction severity. CONCLUSIONS: These results suggest that the disrupted causal interactions between specific regions might contribute to dysfunctions within frontostriatal circuits in IGD, and the pathway from the right OFC to the right caudate could serve as a target for brain modulation in future IGD interventions.

Triple network hypothesis-related disrupted connections in schizophrenia: A spectral dynamic causal modeling analysis with functional magnetic resonance imaging.

OBJECTIVE: The symptom-related neurobiology characteristic of schizophrenia in the brain from a network perspective is still poorly understood, leading to a lack of potential biologically-based markers and difficulty identifying therapeutic targets. We aim to test the dysregulated cross-network interactions among the Salience Network (SN), Central Executive Network (CEN) and Default Mode Network (DMN) and how they contributed to different symptoms in schizophrenia patients. METHODS: We examined network interactions among the SN, CEN and DMN in 76 patients with schizophrenia vs. 80 well-matched controls using dynamic causal modeling (DCM). We further analyzed the relation between network dynamics and Positive and Negative Syndrome Scale (PANSS). RESULTS: We observed that the DMN, CEN and SN across healthy controls and schizophrenia patients showed several similarities within or between-network pattern in the resting state. Comparing schizophrenia to controls, SN-centered cross-network interactions were most significantly reduced. Crucially, the strength of connections from CEN subnetwork 1 to DMN subnetwork 1 was positively correlated with the Positive Score of PANSS. The connection from the DMN subnetwork 2 to CEN subnetwork 2 was negatively correlated with the Negative Score of PANSS. CONCLUSIONS: Our study provides strong evidence for the dysregulation among SN, CEN and DMN in a triple-network perspective in schizophrenia. The connection between DMN and CEN could be clinically-relevant neurobiological signature of schizophrenia symptoms. Our study indicated that the description of brain triple network hypothesis could be a novel and possible bio-marker for schizophrenia.

Altered Effective Connectivity Measured by Resting-State Functional Magnetic Resonance Imaging in Posterior Parietal-Frontal-Striatum Circuit in Patients With Disorder of Consciousness.

OBJECTIVE: Disorder of consciousness (DoC) resulting from severe brain injury is characterized by cortical and subcortical dysconnectivity. However, research on seed-based effective connectivity (EC) of DoC might be questioned as to the heterogeneity of prior assumptions. METHODS: Functional MRI data of 16 DoC patients and 16 demographically matched healthy individuals were analyzed. Revised coma recovery scale (CRS-R) scores of patients were acquired. Seed-based d mapping permutation of subject images (SDM-PSI) of meta-analysis was performed to quantitatively synthesize results from neuroimaging studies that evaluated resting-state functional activity in DoC patients. Spectral dynamic causal modeling (spDCM) was used to assess how EC altered between brain regions in DoC patients compared to healthy individuals. RESULTS: We found increased effective connectivity in left striatum and decreased effective connectivity in bilateral precuneus (preCUN)/posterior cingulate cortex (PCC), bilateral midcingulate cortex and left middle frontal gyrus in DoC compared with the healthy controls. The resulting pattern of interaction in DoC indicated disrupted connection and disturbance of posterior parietal-frontal-striatum, and reduced self-inhibition of preCUN/PCC. The strength of self-inhibition of preCUN/PCC was negatively correlated with the total score of CRS-R. CONCLUSION: This impaired EC in DoC may underlie disruption in the posterior parietal-frontal-striatum circuit, particularly damage to the cortico-striatal connection and possible loss of preCUN/PCC function as the main regulatory hub.

Spectral dynamic causal modelling of resting-state fMRI: an exploratory study relating effective brain connectivity in the default mode network to genetics.

We conduct an imaging genetics study to explore how effective brain connectivity in the default mode network (DMN) may be related to genetics within the context of Alzheimer's disease and mild cognitive impairment. We develop an analysis of longitudinal resting-state functional magnetic resonance imaging (rs-fMRI) and genetic data obtained from a sample of 111 subjects with a total of 319 rs-fMRI scans from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. A Dynamic Causal Model (DCM) is fit to the rs-fMRI scans to estimate effective brain connectivity within the DMN and related to a set of single nucleotide polymorphisms (SNPs) contained in an empirical disease-constrained set which is obtained out-of-sample from 663 ADNI subjects having only genome-wide data. We relate longitudinal effective brain connectivity estimated using spectral DCM to SNPs using both linear mixed effect (LME) models as well as function-on-scalar regression (FSR). In both cases we implement a parametric bootstrap for testing SNP coefficients and make comparisons with p-values obtained from asymptotic null distributions. In both networks at an initial q-value threshold of 0.1 no effects are found. We report on exploratory patterns of associations with relatively high ranks that exhibit stability to the differing assumptions made by both FSR and LME.

Reduced Dynamic Interactions Within Intrinsic Functional Brain Networks in Early Blind Patients.

Neuroimaging studies in early blind (EB) patients have shown altered connections or brain networks. However, it remains unclear how the causal relationships are disrupted within intrinsic brain networks. In our study, we used spectral dynamic causal modeling (DCM) to estimate the causal interactions using resting-state data in a group of 20 EB patients and 20 healthy controls (HC). Coupling parameters in specific regions were estimated, including the medial prefrontal cortex (mPFC), posterior cingulate cortex (PCC), and inferior parietal lobule (IPC) in the default mode network (DMN); dorsal anterior cingulate cortex (dACC) and bilateral anterior insulae (AI) in the salience network (SN), and bilateral frontal eye fields (FEF) and superior parietal lobes (SPL) within the dorsal attention network (DAN). Statistical analyses found that all endogenous connections and the connections from the mPFC to bilateral IPCs in EB patients were significantly reduced within the DMN, and the effective connectivity from the PCC and lIPC to the mPFC, and from the mPFC to the PCC were enhanced. For the SN, all significant connections in EB patients were significantly decreased, except the intrinsic right AI connections. Within the DAN, more significant effective connections were observed to be reduced between the EB and HC groups, while only the connections from the right SPL to the left SPL and the intrinsic connection in the left SPL were significantly enhanced. Furthermore, discovery of more decreased effective connections in the EB subjects suggested that the disrupted causal interactions between specific regions are responsive to the compensatory brain plasticity in early deprivation.

Effective connectivity changes in LSD-induced altered states of consciousness in humans.

Psychedelics exert unique effects on human consciousness. The thalamic filter model suggests that core effects of psychedelics may result from gating deficits, based on a disintegration of information processing within cortico-striato-thalamo-cortical (CSTC) feedback loops. To test this hypothesis, we characterized changes in directed (effective) connectivity between selected CTSC regions after acute administration of lysergic acid diethylamide (LSD), and after pretreatment with Ketanserin (a selective serotonin 2A receptor antagonist) plus LSD in a double-blind, randomized, placebo-controlled, cross-over study in 25 healthy participants. We used spectral dynamic causal modeling (DCM) for resting-state fMRI data. Fully connected DCM models were specified for each treatment condition to investigate the connectivity between the following areas: thalamus, ventral striatum, posterior cingulate cortex, and temporal cortex. Our results confirm major predictions proposed in the CSTC model and provide evidence that LSD alters effective connectivity within CSTC pathways that have been implicated in the gating of sensory and sensorimotor information to the cortex. In particular, LSD increased effective connectivity from the thalamus to the posterior cingulate cortex in a way that depended on serotonin 2A receptor activation, and decreased effective connectivity from the ventral striatum to the thalamus independently of serotonin 2A receptor activation. Together, these results advance our mechanistic understanding of the action of psychedelics in health and disease. This is important for the development of new pharmacological therapeutics and also increases our understanding of the mechanisms underlying the potential clinical efficacy of psychedelics.

Mapping Internet gaming disorder using effective connectivity: A spectral dynamic causal modeling study.

OBJECTS: Understanding the neural basis underlying Internet gaming disorder (IGD) is essential for the diagnosis and treatment of this type of behavioural addiction. Aberrant resting-state functional connectivity (rsFC) of the default mode network (DMN) has been reported in individuals with IGD. Since rsFC is not a directional analysis, the effective connectivity within the DMN in IGD remains unclear. Here, we employed spectral dynamic causal modeling (spDCM) to explore this issue. METHODS: Resting state fMRI data were collected from 64 IGD (age: 22.6 ±â€¯2.2) and 63 well-matched recreational Internet game users (RGU, age: 23.1 ±â€¯2.5). Voxel-based mean time series data extracted from the 4 brain regions within the DMN (medial prefrontal cortex, mPFC; posterior cingulate cortex, PCC; bilateral inferior parietal lobule, left IPL/right IPL) of two groups during the resting state were used for the spDCM analysis. RESULTS: Compared with RGU, IGD showed reduced effective connectivity from the mPFC to the PCC and from the left IPL to the mPFC, with reduced self-connection in the PCC and the left IPL. CONCLUSIONS: The spDCM could distinguish the changes in the functional architecture between two groups more precisely than rsFC. Our findings suggest that the decreased excitatory connectivity from the mPFC to the PCC may be a crucial biomarker for IGD. Future brain-based intervention should pay attention to dysregulation in the IPL-mPFC-PCC circuits.

Abnormal Effective Connectivity of the Anterior Forebrain Regions in Disorders of Consciousness.

A number of studies have indicated that disorders of consciousness result from multifocal injuries as well as from the impaired functional and anatomical connectivity between various anterior forebrain regions. However, the specific causal mechanism linking these regions remains unclear. In this study, we used spectral dynamic causal modeling to assess how the effective connections (ECs) between various regions differ between individuals. Next, we used connectome-based predictive modeling to evaluate the performance of the ECs in predicting the clinical scores of DOC patients. We found increased ECs from the striatum to the globus pallidus as well as from the globus pallidus to the posterior cingulate cortex, and decreased ECs from the globus pallidus to the thalamus and from the medial prefrontal cortex to the striatum in DOC patients as compared to healthy controls. Prediction of the patients' outcome was effective using the negative ECs as features. In summary, the present study highlights a key role of the thalamo-basal ganglia-cortical loop in DOCs and supports the anterior forebrain mesocircuit hypothesis. Furthermore, EC could be potentially used to assess the consciousness level.

Multivariate Classification of Major Depressive Disorder Using the Effective Connectivity and Functional Connectivity.

Major depressive disorder (MDD) is a mental disorder characterized by at least 2 weeks of low mood, which is present across most situations. Diagnosis of MDD using rest-state functional magnetic resonance imaging (fMRI) data faces many challenges due to the high dimensionality, small samples, noisy and individual variability. To our best knowledge, no studies aim at classification with effective connectivity and functional connectivity measures between MDD patients and healthy controls. In this study, we performed a data-driving classification analysis using the whole brain connectivity measures which included the functional connectivity from two brain templates and effective connectivity measures created by the default mode network (DMN), dorsal attention network (DAN), frontal-parietal network (FPN), and silence network (SN). Effective connectivity measures were extracted using spectral Dynamic Causal Modeling (spDCM) and transformed into a vectorial feature space. Linear Support Vector Machine (linear SVM), non-linear SVM, k-Nearest Neighbor (KNN), and Logistic Regression (LR) were used as the classifiers to identify the differences between MDD patients and healthy controls. Our results showed that the highest accuracy achieved 91.67% (p < 0.0001) when using 19 effective connections and 89.36% when using 6,650 functional connections. The functional connections with high discriminative power were mainly located within or across the whole brain resting-state networks while the discriminative effective connections located in several specific regions, such as posterior cingulate cortex (PCC), ventromedial prefrontal cortex (vmPFC), dorsal cingulate cortex (dACC), and inferior parietal lobes (IPL). To further compare the discriminative power of functional connections and effective connections, a classification analysis only using the functional connections from those four networks was conducted and the highest accuracy achieved 78.33% (p < 0.0001). Our study demonstrated that the effective connectivity measures might play a more important role than functional connectivity in exploring the alterations between patients and health controls and afford a better mechanistic interpretability. Moreover, our results showed a diagnostic potential of the effective connectivity for the diagnosis of MDD patients with high accuracies allowing for earlier prevention or intervention.

Altered Resting State Effective Connectivity of Anterior Insula in Depression.

Depression has been associated with changes in both functional and effective connectivity of large scale brain networks, including the default mode network, executive network, and salience network. However, studies of effective connectivity by means of spectral dynamic causal modeling (spDCM) are still rare and the interaction between the different resting state networks has not been investigated in detail. Thus, we aimed at exploring differences in effective connectivity among eight right hemisphere brain areas-anterior insula, inferior frontal gyrus, middle frontal gyrus (MFG), frontal eye field, anterior cingulate cortex, superior parietal lobe, amygdala, and hippocampus, between a group of healthy controls (N = 20) and medicated depressed patients (N = 20). We found that patients not only had significantly reduced strength of the connection from the anterior insula to the MFG (i.e., dorsolateral prefrontal cortex) but also a significant connection between the amygdala and the anterior insula. Moreover, depression severity correlated with connectivity of the hippocampal node. In conclusion, the results from this resting state spDCM study support and enrich previous data on the role of the right anterior insula in the pathophysiology of depression. Furthermore, our findings add to the growing evidence of an association between depression severity and disturbances of the hippocampal function in terms of impaired connectivity with other brain regions.

Prefrontal dysconnectivity links to working memory deficit in first-episode schizophrenia.

Working memory (WM) deficit is a core feature of schizophrenia and is characterized by abnormal functional integration in the prefrontal cortex, including the dorsolateral prefrontal cortex (dLPFC), dorsal anterior cingulate cortex (dACC), and ventrolateral prefrontal cortex (vLPFC). However, the specific mechanism by which the abnormal neuronal circuits that involve these brain regions contribute to this deficit is still unclear. Therefore, this study focused on these regions and sought to answer which abnormal causal relationships in these regions can be linked to impaired WM in schizophrenia. We used spectral dynamic causal modeling to estimate directed (effective) connectivity between these regions based on resting-state functional magnetic resonance imaging data from healthy control (HC) subjects and patients with first-episode schizophrenia (FES). By comparing these effective connections in the controls and patients, we found that the effective connectivity from the dACC to the dLPFC and from the right dLPFC to the left vLPFC was weaker in the FES group than in the HC group. Furthermore, these effective connections displayed a positive correlation with WM performance in the HCs. However, in the FES patients, the effective connectivity from the dACC to the dLPFC was not correlated with WM performance, and the effective connectivity from the right dLPFC to the left vLPFC was negatively correlated with WM performance. These results could be explained by an aberrant top-down mechanism of WM processing and provide new evidence for the dysconnectivity hypothesis of schizophrenia.

Abnormal Effective Connectivity of the Anterior Forebrain Regions in Disorders of Consciousness / 神经科学通报·英文版

A number of studies have indicated that disorders of consciousness result from multifocal injuries as well as from the impaired functional and anatomical connectivity between various anterior forebrain regions. However, the specific causal mechanism linking these regions remains unclear. In this study, we used spectral dynamic causal modeling to assess how the effective connections (ECs) between various regions differ between individuals. Next, we used connectome-based predictive modeling to evaluate the performance of the ECs in predicting the clinical scores of DOC patients. We found increased ECs from the striatum to the globus pallidus as well as from the globus pallidus to the posterior cingulate cortex, and decreased ECs from the globus pallidus to the thalamus and from the medial prefrontal cortex to the striatum in DOC patients as compared to healthy controls. Prediction of the patients' outcome was effective using the negative ECs as features. In summary, the present study highlights a key role of the thalamo-basal ganglia-cortical loop in DOCs and supports the anterior forebrain mesocircuit hypothesis. Furthermore, EC could be potentially used to assess the consciousness level.