Aberrant Dependence of Default Mode/Central Executive Network Interactions on Anterior Insular Salience Network Activity in Schizophrenia

In schizophrenia, consistent structural and functional changes have been demonstrated for the insula including aberrant salience processing, which is critical for psychosis. Interactions within and across default mode and central executive network (DMN, CEN) are impaired in schizophrenia. The question arises whether these 2 types of changes are related. Recently, the anterior insula has been demonstrated to control DMN/CEN interactions. We hypothesized that aberrant insula and DMN/CEN activity in schizophrenia is associated with an impaired dependence of DMN/CEN interactions on anterior insular salience network (SN) activity. Eighteen patients with schizophrenia during psychosis and 20 healthy controls were studied by resting-state-fMRI and psychometric examination. High-model-order independent component analysis of fMRI data revealed spatiotemporal patterns of synchronized ongoing blood-oxygenation-level-dependent (BOLD) activity including SN, DMN, and CEN. Scores of functional and time-lagged connectivity across networks’ time courses were calculated. Connectivity scores and spatial network maps were compared between groups and related with patients’ hallucination and delusion severity. Spatial BOLD-synchronicity was altered in patients’ SN, DMN, and CEN, including decreased activity in the right anterior insula (rAI). Patients’ functional connectivity between DMN and CEN was increased and related with hallucinations severity. Importantly, patients’ time-lagged connectivity between SN and DMN/CEN was reduced, and decreased rAI activity of the SN was associated with both hallucinations and increased functional connectivity between DMN and CEN. Data provide evidence for an aberrant dependence of DMN/CEN interactions on anterior insular SN activity, linking impaired insula, DMN, CEN activity, and psychosis in schizophrenia.Key words: schizophrenia, psychosis, anterior insula, salience network, default mode network, central executive network     

Increased functional connectivity between the default mode and salience networks in unmedicated adults with obsessive‐compulsive disorder

Deficits in attention have been implicated in Obsessive‐Compulsive Disorder (OCD), yet their neurobiological bases are poorly understood. In unmedicated adults with OCD (n = 30) and healthy controls (n = 32), they used resting state functional connectivity MRI (rs‐fcMRI) to examine functional connectivity between two neural networks associated with attentional processes: the default mode network (DMN) and the salience network (SN). They then used path analyses to examine putative relationships across three variables of interest: DMN‐SN connectivity, attention, and OCD symptoms. In the OCD compared with healthy control participants, there was significantly reduced inverse connectivity between the anterior medial prefrontal cortex (amPFC) and the anterior insular cortex, regions within the DMN and SN, respectively. In OCD, reduced inverse DMN‐SN connectivity was associated with both increased OCD symptom severity and decreased sustained attention. Path analyses were consistent with a potential mechanistic explanation: OCD symptoms are associated with an imbalance in DMN‐SN networks that subserve attentional processes and this effect of OCD on DMN‐SN connectivity is associated with decreased sustained attention. This work builds upon a growing literature suggesting that reduced inverse DMN‐SN connectivity may represent a trans‐diagnostic marker of attentional processes and suggests a potential mechanistic account of the relationship between OCD and attention. Reduced inverse DMN‐SN connectivity may be an important target for treatment development to improve attention in individuals with OCD. Hum Brain Mapp 38:678–687, 2017. © 2016 Wiley Periodicals, Inc.     

Functional disconnection of the right anterior insula in obstructive sleep apnea

BackgroundThe right anterior insula (AIns) is an important node of the salience network and serves to switch between two major cognitive-related functional brain networks, ie, the central executive network (CEN) and the default mode network (DMN), both of which show functional deficits in obstructive sleep apnea (OSA) patients. However, the effect of OSA on functional connectivity of the right AIns remains uncertain.ObjectiveTo determine whether the resting-state functional connectivity (rsFC) between the right AIns and the CEN and DMN is disrupted in OSA patients, which may be associated with cognitive deficits in this disorder.MethodsTwenty-four male OSA patients and 21 matched healthy controls underwent functional MRI examinations and clinical and neuropsychologic assessments. The rsFCs between the right AIns and the CEN and DMN were compared between the two groups and were correlated with clinical and neuropsychologic assessments.ResultsCompared with healthy controls, OSA patients showed significantly weakened rsFC between the right AIns and the DMN. Moreover, the functional disconnection between the right AIns and the medial prefrontal cortex was correlated with the severity of the OSA; and the functional disconnection between the right AIns and the posterior cingulate cortex was correlated with depressive scores and working memory performance. However, there were no significant inter-group differences in the rsFC between the right AIns and the CEN.ConclusionsThese findings suggest that OSA selectively impairs the rsFC between the right AIns and the DMN, which may be a candidate substrate for cognitive impairment in OSA patients.     

Recreational use of GHB is associated with alterations of resting state functional connectivity of the central executive and default mode networks

Gamma‐hydroxybutyrate acid (GHB) is a recreational drug with a high addictive potential. Severe side effects such as GHB‐induced coma are common and linked to increased emergency room attendances. Task‐based functional‐imaging studies have revealed an association between the regular use of GHB and multiple GHB‐induced comas, and altered neurocognitive function. However the effects of multiple GHB‐induced comas and regular GHB‐use on intrinsic brain connectivity during rest remain unknown. The study population consisted of 23 GHB‐users with ≥4 GHB‐induced comas (GHB‐Coma), 22 GHB‐users who never experienced a GHB‐induced coma (GHB‐NoComa) and 24 polydrug users who never used GHB (No‐GHB). Resting‐state scans were collected to assess resting‐state functional‐connectivity within and between the default mode network (DMN), the bilateral central executive network (CEN) and the salience network (SN). The GHB‐NoComa group showed decreased rsFC of the right CEN with a region in the anterior cingulate cortex (p_FWE = 0.048) and decreased rsFC between the right CEN and the DMN (p_FWE = 0.048) when compared with the No‐GHB group. These results suggest that regular GHB‐use is associated with decreased rsFC within the right CEN and between the right CEN and the DMN. The presence of multiple GHB‐induced comas is not associated with (additional) alterations in rsFC.     

Functional connectivity and neuronal variability of resting state activity in bipolar disorder—reduction and decoupling in anterior cortical midline structures

Introduction: The cortical midline structures seem to be involved in the modulation of different resting state networks, such as the default mode network (DMN) and salience network (SN). Alterations in these systems, in particular in the perigenual anterior cingulate cortex (PACC), seem to play a central role in bipolar disorder (BD). However, the exact role of the PACC, and its functional connections to other midline regions (within and outside DMN) still remains unclear in BD. Methods: We investigated functional connectivity (FC), standard deviation (SD, as a measure of neuronal variability) and their correlation in bipolar patients (n = 40) versus healthy controls (n = 40), in the PACC and in its connections in different frequency bands (standard: 0.01–0.10 Hz; Slow‐5: 0.01–0.027 Hz; Slow‐4: 0.027–0.073 Hz). Finally, we studied the correlations between FC alterations and clinical‐neuropsychological parameters and we explored whether subgroups of patients in different phases of the illness present different patterns of FC abnormalities. Results: We found in BD decreased FC (especially in Slow‐5) from the PACC to other regions located predominantly in the posterior DMN (such as the posterior cingulate cortex (PCC) and inferior temporal gyrus) and in the SN (such as the supragenual anterior cingulate cortex and ventrolateral prefrontal cortex). Second, we found in BD a decoupling between PACC‐based FC and variability in the various target regions (without alteration in variability itself). Finally, in our subgroups explorative analysis, we found a decrease in FC between the PACC and supragenual ACC (in depressive phase) and between the PACC and PCC (in manic phase). Conclusions: These findings suggest that in BD the communication, that is, information transfer, between the different cortical midline regions within the cingulate gyrus does not seem to work properly. This may result in dysbalance between different resting state networks like the DMN and SN. A deficit in the anterior DMN‐SN connectivity could lead to an abnormal shifting toward the DMN, while a deficit in the anterior DMN‐posterior DMN connectivity could lead to an abnormal shifting toward the SN, resulting in excessive focusing on internal contents and reduced transition from idea to action or in excessive focusing on external contents and increased transition from idea to action, respectively, which could represent central dimensions of depression and mania. If confirmed, they could represent diagnostic markers in BD. Hum Brain Mapp 36:666–682, 2015. © 2014 Wiley Periodicals, Inc.     

Disrupted functional connectivity of default mode and salience networks in chronic pancreatitis patients

ObjectiveThe functional connectivity of the brain in chronic pancreatitis (CP) remains unknown. This study aimed to investigate functional connectivity in CP patients using resting state functional magnetic resonance imaging (fMRI) and explore the associations to clinical parameters and altered cerebral metabolites.MethodsSeed-based and ROI-to-ROI analyses were performed to assess connectivity within and between the default mode network (DMN) and salience network (SN). Additionally, functional connectivity in these networks were investigated in relation to clinical parameters (CP etiology, pain, medication, etc.) and cerebral glutamate/creatine level in the anterior cingulate cortex.ResultsThirty CP patients and 23 healthy controls were analyzed. CP patients showed hyper-connectivity in DMN and SN as compared to healthy controls. Furthermore, CP patients had reduced anti-correlated functional connectivity between DMN and SN (all P ≤ 0.009). The altered DMN connectivity correlated to glutamate/creatine level (r = 0.503, P = 0.020) in patients with pain, but not to the clinical parameters.ConclusionsCP patients had altered functional connectivity within and between brain networks. Altered DMN functional connectivity had an association to cerebral metabolic changes.SignificanceAltered functional connectivity in CP share similarities with other chronic pain conditions, and support our understanding of altered brain circuitry associated with the CP disease.     

Changes in Default-Mode Network Associated With Childhood Trauma in Schizophrenia

BackgroundThere is considerable evidence of dysconnectivity within the default-mode network (DMN) in schizophrenia, as measured during resting-state functional MRI (rs-fMRI). History of childhood trauma (CT) is observed at a higher frequency in schizophrenia than in the general population, but its relationship to DMN functional connectivity has yet to be investigated.MethodsCT history and rs-fMRI data were collected in 65 individuals with schizophrenia and 132 healthy controls. Seed-based functional connectivity between each of 4 a priori defined seeds of the DMN (medial prefrontal cortex, right and left lateral parietal lobes, and the posterior cingulate cortex) and all other voxels of the brain were compared across groups. Effects of CT on functional connectivity were examined using multiple regression analyses. Where significant associations were observed, regression analyses were further used to determine whether variance in behavioral measures of Theory of Mind (ToM), previously associated with DMN recruitment, were explained by these associations.ResultsSeed-based analyses revealed evidence of widespread reductions in functional connectivity in patients vs controls, including between the left/right parietal lobe (LP) and multiple other regions, including the parietal operculum bilaterally. Across all subjects, increased CT scores were associated with reduced prefrontal-parietal connectivity and, in patients, with increased prefrontal-cerebellar connectivity also. These CT-associated differences in DMN connectivity also predicted variation in behavioral measures of ToM.ConclusionsThese findings suggest that CT history is associated with variation in DMN connectivity during rs-fMRI in patients with schizophrenia and healthy participants, which may partly mediate associations observed between early life adversity and cognitive performance.     

Functional connectivity of the attention networks is altered and relates to neuropsychological outcomes in children with prenatal alcohol exposure

Cognitive and functional brain alterations can occur in children with prenatal alcohol exposure (PAE). We examined the functional connectivity (FC) among regions within and between attention networks, and whether inter- and intranetwork FC moderated cognition in children with PAE (n = 37; age 12.8 ± 2.8 years) and nonexposed controls (n = 40; age 13.2 ± 2.8 years). Participants completed standardized attention and executive functioning tasks and resting state functional MRI. Inter- and intra-network FC and graph-theoretical metrics were calculated among attention network regions. Relative to controls, PAE was associated with reduced FC between the left temporoparietal junction and left ventral frontal cortex and anterior insula/frontal operculum (aI/fO), and between the left intraparietal sulcus and bilateral aI/fO. PAE was associated with increased FC between the right precuneus and intraparietal lobes, the right anterior prefrontal cortex and left ventral frontal cortex and aI/fO, and the left thalamus and dorsal frontal cortex. Graph-theoretical metrics did not differ by group. FC predicted cognitive performance, negatively in the children with PAE and positively in controls. Increased intra-network together with reduced internetwork FC suggests inefficient network specialization and impaired long-range FC among attention network regions after PAE. Results further suggest that those alterations may underlie attention and executive dysfunction in children with PAE.     

“临床治愈”抑郁症患者默认网络静息态功能连接研究

目的:结合静息态功能连接方法,探讨"临床治愈"抑郁症(remitted major depressive disorder,r MDD)患者默认网络(default mode network,DMN)功能连接的变化。方法:对22例经过住院治疗达到r MDD标准的患者(患者组)和22名相匹配正常对照组进行静息态功能磁共振扫描,以DMN公认的内侧前额叶(medial prefrontal cortex,m PFC)和后扣带回(posterior cingulate cortex,PCC)为种子点,通过种子点与全脑的功能连接分析,使用双样本t检验比较两组的功能连接差异。结果:与正常对照组比较,患者组m PFC与右侧角回(t=3.96,P0.01)、右侧旁扣带回(t=4.57,P0.01)、右侧额下回(t=4.25,P0.01)功能连接增加,与左侧前扣带回(t=-3.50,P0.01)、右侧PCC(t=-3.57,P0.01)功能连接降低;PCC与左侧枕中回(t=3.47,P0.01)、右侧枕中回(t=4.18,P0.01)功能连接增加。结论:r MDD患者DMN功能连接仍存在异常,可能与反刍症状及注意等认知偏向未完全改善有关。     

Functional reorganization of intra‐ and internetwork connectivity in major depressive disorder after electroconvulsive therapy

Electroconvulsive therapy (ECT) is an effective and rapid treatment for major depressive disorder (MDD). However, the neurobiological underpinnings of ECT are still largely unknown. Recent studies have identified dysregulated brain networks in MDD. Therefore, we hypothesized that ECT may improve MDD symptoms through reorganizing these networks. To test this hypothesis, we used resting‐state functional connectivity to investigate changes to the intra‐ and internetwork architecture of five reproducible resting‐state networks: the default mode network (DMN), dorsal attention network (DAN), executive control network (CON), salience network (SAL), and sensory‐motor network. Twenty‐three MDD patients were assessed before and after ECT, along with 25 sex‐, age‐, and education‐matched healthy controls. At the network level, enhanced intranetwork connectivities were found in the CON in MDD patients after ECT. Furthermore, enhanced internetwork connectivities between the DMN and SAL, and between the CON and DMN, DAN, and SAL were also identified. At the nodal level, the posterior cingulate cortex had increased connections with the left posterior cerebellum, right posterior intraparietal sulcus (rpIPS), and right anterior prefrontal cortex. The rpIPS had increased connections with the medial PFC (mPFC) and left anterior cingulate cortex. The left lateral parietal had increased connections with the dorsal mPFC (dmPFC), left anterior prefrontal cortex, and right anterior cingulate cortex. The dmPFC had increased connection with the left anterolateral prefrontal cortex. Our findings indicate that enhanced interactions in intra‐ and internetworks may contribute to the ECT response in MDD patients. These findings provide novel and important insights into the neurobiological mechanisms underlying ECT.     

Abnormal salience network in normal aging and in amnestic mild cognitive impairment and Alzheimer's disease

The salience network (SN) serves to identify salient stimuli and to switch between the central executive network (CEN) and the default‐mode network (DMN), both of which are impaired in Alzheimer's disease (AD)/amnestic mild cognitive impairment (aMCI). We hypothesized that both the structural and functional organization of the SN and functional interactions between the SN and CEN/DMN are altered in normal aging and in AD/aMCI. Gray matter volume (GMV) and resting‐state functional connectivity (FC) were analyzed from healthy younger (HYC) to older controls (HOC) and from HOC to aMCI and AD patients. All the SN components showed significant differences in the GMV, intranetwork FC, and internetwork FC between the HYC and HOC. Most of the SN components showed differences in the GMV between the HOC and AD and between the aMCI and AD. Compared with the HOC, AD patients exhibited significant differences in intra‐ and internetwork FCs of the SN, whereas aMCI patients demonstrated differences in internetwork FC of the SN. Most of the GMVs and internetwork FCs of the SN and part of the intranetwork FC of the SN were correlated with cognitive differences in older subjects. Our findings suggested that structural and functional impairments of the SN may occur as early as in normal aging and that functional disconnection between the SN and CEN/ DMN may also be associated with both normal aging and disease progression. Hum Brain Mapp 35:3446–3464, 2014. © 2013 Wiley Periodicals, Inc .     

Multiple Network Dysconnectivity in Adolescents with Psychotic Experiences: A Longitudinal Population-Based Study

Abnormal functional connectivity (FC, the temporal synchronization of activation across distinct brain regions) of the default mode (DMN), salience (SN), central executive (CEN), and motor (MN) networks is well established in psychosis. However, little is known about FC in individuals, particularly adolescents, reporting subthreshold psychotic experiences (PE) and their trajectory over time. Thus, the aim of this study was to investigate the FC of these networks in adolescents with PE. In this population-based case-control study, 24 adolescents (mean age = 13.58) meeting the criteria for PE were drawn from a sample of 211 young people recruited and scanned for a neuroimaging study, with a follow-up scan 2 years later (n = 18, mean age = 15.78) and compared to matched controls drawn from the same sample. We compared FC of DMN, SN, CEN, and MN regions between PE and controls using whole-brain FC analyses. At both timepoints, the PE group displayed significant hypoconnectivity compared to controls. At baseline, FC in the PE group was decreased between MN and DMN regions. At follow-up, dysconnectivity in the PE group was more widespread. Over time, controls displayed greater FC changes than the PE group, with FC generally increasing between MN, DMN, and SN regions. Adolescents with PE exhibit hypoconnectivity across several functional networks also found to be hypoconnected in established psychosis. Our findings highlight the potential for studies of adolescents reporting PE to reveal early neural correlates of psychosis and support further investigation of the role of the MN in PE and psychotic disorders.     

Multimodal investigation of triple network connectivity in patients with 22q11DS and association with executive functions

Large‐scale brain networks play a prominent role in cognitive abilities and their activity is impaired in psychiatric disorders, such as schizophrenia. Patients with 22q11.2 deletion syndrome (22q11DS) are at high risk of developing schizophrenia and present similar cognitive impairments, including executive functions deficits. Thus, 22q11DS represents a model for the study of neural biomarkers associated with schizophrenia. In this study, we investigated structural and functional connectivity within and between the Default Mode (DMN), the Central Executive (CEN), and the Saliency network (SN) in 22q11DS using resting‐state fMRI and DTI. Furthermore, we investigated if triple network impairments were related to executive dysfunctions or the presence of psychotic symptoms. Sixty‐three patients with 22q11DS and sixty‐eighty controls (age 6–33 years) were included in the study. Structural connectivity between main nodes of DMN, CEN, and SN was computed using probabilistic tractography. Functional connectivity was computed as the partial correlation between the time courses extracted from each node. Structural and functional connectivity measures were then correlated to executive functions and psychotic symptom scores. Our results showed mainly reduced structural connectivity within the CEN, DMN, and SN, in patients with 22q11DS compared with controls as well as reduced between‐network connectivity. Functional connectivity appeared to be more preserved, with impairments being evident only within the DMN. Structural connectivity impairments were also related to executive dysfunctions. These findings show an association between triple network structural alterations and executive deficits in patients with the microdeletion, suggesting that 22q11DS and schizophrenia share common psychopathological mechanisms. Hum Brain Mapp 38:2177–2189, 2017. © 2017 Wiley Periodicals, Inc.     

Different shades of default mode disturbance in schizophrenia: Subnodal covariance estimation in structure and function

Schizophrenia is a devastating mental disease with an apparent disruption in the highly associative default mode network (DMN). Interplay between this canonical network and others probably contributes to goal‐directed behavior so its disturbance is a candidate neural fingerprint underlying schizophrenia psychopathology. Previous research has reported both hyperconnectivity and hypoconnectivity within the DMN, and both increased and decreased DMN coupling with the multimodal saliency network (SN) and dorsal attention network (DAN). This study systematically revisited network disruption in patients with schizophrenia using data‐derived network atlases and multivariate pattern‐learning algorithms in a multisite dataset (n = 325). Resting‐state fluctuations in unconstrained brain states were used to estimate functional connectivity, and local volume differences between individuals were used to estimate structural co‐occurrence within and between the DMN, SN, and DAN. In brain structure and function, sparse inverse covariance estimates of network coupling were used to characterize healthy participants and patients with schizophrenia, and to identify statistically significant group differences. Evidence did not confirm that the backbone of the DMN was the primary driver of brain dysfunction in schizophrenia. Instead, functional and structural aberrations were frequently located outside of the DMN core, such as in the anterior temporoparietal junction and precuneus. Additionally, functional covariation analyses highlighted dysfunctional DMN‐DAN coupling, while structural covariation results highlighted aberrant DMN‐SN coupling. Our findings reframe the role of the DMN core and its relation to canonical networks in schizophrenia. We thus underline the importance of large‐scale neural interactions as effective biomarkers and indicators of how to tailor psychiatric care to single patients.     

Decreased anticipated pleasure correlates with increased salience network resting state functional connectivity in adolescents with depressive symptomatology

Previous studies have found dysfunctional resting state functional connectivity (RSFC) in depressed patients. Examining RSFC might aid biomarker discovery for depression. However RSFC in young people at risk of depression has yet to be examined.35 healthy adolescents (13–18 yrs old.) were recruited. 17 scoring high on the Mood and Feelings Questionnaire (MFQ > 27 (High Risk: HR), and 18 scoring low on the MFQ < 15 (Low Risk: LR) matched on age and gender. We selected seed regions in the salience network (SN: amygdala and pregenual anterior cingulate cortex (pgACC)) and the central executive network (CEN: dorsal medial prefrontal cortex (dmPFC)). Mood and anhedonia measures were correlated with brain connectivity.We found decreased RSFC in the HR group between the amygdala and the pgACC and hippocampus and precuneus. We also found decreased RSFC in the HR group between the pgACC and the putamen and between the dmPFC and the precuneus. The pgACC RSFC with the insula/orbitofrontal cortex correlated inversely with the anticipation of pleasure in all subjects. Increased RSFC was observed between the pgACC and the prefrontal cortex and the amygdala and the temporal pole in the HR group compared to the LR group.Our findings are the first to show that adolescents with depression symptoms have dysfunctional RSFC between seeds in the SN and CEN with nodes in the Default Mode Network. As increased connectivity between the pgACC and the insula correlated with decreased ability to anticipate pleasure, we suggest this might be mechanism underlying the risk of experiencing anhedonia, a suggested biomarker for depression.     

Discriminating stress from rest based on resting‐state connectivity of the human brain: A supervised machine learning study

Acute stress induces large‐scale neural reorganization with relevance to stress‐related psychopathology. Here, we applied a novel supervised machine learning method, combining the strengths of a priori theoretical insights with a data‐driven approach, to identify which connectivity changes are most prominently associated with a state of acute stress and individual differences therein. Resting‐state functional magnetic resonance imaging scans were taken from 334 healthy participants (79 females) before and after a formal stress induction. For each individual scan, mean time‐series were extracted from 46 functional parcels of three major brain networks previously shown to be potentially sensitive to stress effects (default mode network (DMN), salience network (SN), and executive control networks). A data‐driven approach was then used to obtain discriminative spatial linear filters that classified the pre‐ and post‐stress scans. To assess potential relevance for understanding individual differences, probability of classification using the most discriminative filters was linked to individual cortisol stress responses. Our model correctly classified pre‐ versus post‐stress states with highly significant accuracy (above 75%; leave‐one‐out validation relative to chance performance). Discrimination between pre‐ and post‐stress states was mainly based on connectivity changes in regions from the SN and DMN, including the dorsal anterior cingulate cortex, amygdala, posterior cingulate cortex, and precuneus. Interestingly, the probability of classification using these connectivity changes were associated with individual cortisol increases. Our results confirm the involvement of DMN and SN using a data‐driven approach, and specifically single out key regions that might receive additional attention in future studies for their relevance also for individual differences.     

Frontoparietal and default mode network connectivity varies with age and intelligence

BackgroundAnticorrelated resting state connectivity between task-positive and task-negative networks in adults supports flexible shifting between externally focused attention and internal thought. Findings suggest that children show positive correlations between task-positive (frontoparietal; FP) and task-negative (default mode; DMN) networks. FP-DMN connectivity also associates with intellectual functioning across the lifespan. We investigated whether FP-DMN connectivity in healthy children varied with age and intelligence quotient (IQ).MethodsWe utilized network-based statistics (NBS) to examine resting state functional connectivity between FP and DMN seeds in N = 133 7−25-year-olds (M_age = 15.80). Linear regression evaluated FP-DMN associations with IQ.ResultsWe detected NBS subnetworks containing both within- and between-network connections that were inversely associated with age. Four FP-DMN connections showed more negative connectivity between FP (inferior frontal gyrus and precentral gyrus) and DMN regions (frontal medial cortex, precuneus, and frontal pole) among older participants. Frontal pole-precentral gyrus connectivity inversely associated with IQ.ConclusionsFP-DMN connectivity was more anticorrelated at older ages, potentially indicating dynamic network segregation of these circuits from childhood to early adulthood. Youth with more mature (i.e., anticorrelated) FP-DMN connectivity demonstrated higher IQ. Our findings add to the growing body of literature examining neural network development and its association with IQ.     

Aberrant Coupling Within and Across the Default Mode,Task-Positive,and Salience Network in Subjects at Risk for Psychosis

The task-positive network (TPN) is anticorrelated with activity in the default mode network (DMN), and possibly reflects competition between the processing of external and internal information, while the salience network (SN) is pivotal in regulating TPN and DMN activity. Because abnormal functional connectivity in these networks has been related to schizophrenia, we tested whether alterations are also evident in subjects at risk for psychosis. Resting-state functional magnetic resonance imaging was tested in 28 subjects with basic symptoms reporting subjective cognitive-perceptive symptoms; 19 with attenuated or brief, limited psychotic symptoms; and 29 matched healthy controls. We characterized spatial differences in connectivity patterns, as well as internetwork connectivity. Right anterior insula (rAI) was selected as seed region for identifying the SN; medioprefrontal cortex (MPFC) for the DMN and TPN. The 3 groups differed in connectivity patterns between the MPFC and right dorsolateral prefrontal cortex (rDLPFC), and between the rAI and posterior cingulate cortex (PCC). In particular, the typically observed antagonistic relationship in MPFC-rDLPFC, rAI-PCC, and internetwork connectivity of DMN-TPN was absent in both at-risk groups. Notably, those connectivity patterns were associated with symptoms related to reality distortions, whereas enhanced connectivity strengths of MPFC-rDLPFC and TPN-DMN were related to poor performance in cognitive functions. We propose that the loss of a TPN-DMN anticorrelation, accompanied by an aberrant spatial extent in the DMN, TPN, and SN in the psychosis risk state, reflects the confusion of internally and externally focused states and disturbance of cognition, as seen in psychotic disorders.Key words: resting-state fMRI, schizophrenia, anticorrelated networks, functional connectivity, central executive network, anterior insula, prodrome, intrinsic connectivity, brain     

首次发病且未用药的成年早发和晚发抑郁症患者脑功能连接差异研究

目的比较成年早发抑郁症(EOD)和成年晚发抑郁症(LOD)患者默认网络(DMN)内部功能连接的差异,探究不同发病年龄的抑郁症患者是否有不同的发病机制。方法选取在昆明医科大学第一附属医院精神科门诊或住院的EOD患者(n=58)和LOD患者(n=62)为研究对象,同期招募年轻健康对照组(n=60)和年老健康对照组(n=52)。对受试者进行静息态功能磁共振扫描,选择左侧楔前叶为种子点,计算该种子点与全脑的功能连接,并比较各组间该种子点的功能连接差异。结果四组之间功能连接具有差异的脑区涉及双侧额叶、颞叶、基底节、枕叶、顶叶及小脑等脑区。EOD组左侧楔前叶与左侧小脑Crus1区、左侧小脑IX区、左侧颞中回、右侧楔前叶、右侧前扣带回、右侧额中回、右侧角回、右侧脑岛、右侧内侧额上回、右侧颞中回的功能连接均高于年轻健康对照组(Z=3. 752 4～5. 867 8,P均0. 05);而左侧楔前叶与左侧额中回、左侧中央旁小叶、右侧缘上回、右侧额上回、右侧颞下回、右侧中央后回、右侧中央前回、右侧枕上回的功能连接均低于年轻健康对照组(Z=-5. 007 6～-3. 797 7,P均0. 05)。LOD组左侧楔前叶与左侧小脑Crus2区、左侧尾状核、左侧颞下回、左侧小脑Crus1区、左侧角回、左侧额中回、右侧额中回、右侧角回、右侧眶额部额中回的功能连接均高于年老健康对照组(Z=4. 122 8～6. 579 4,P均0. 05);与左侧海马旁回、左侧额上回、右侧枕中回、右侧中央前回、右侧内侧额上回、右侧锯状回、右侧颞下回、右侧中央旁小叶、右侧梭状回、右侧后扣带回的功能连接均低于年老健康对照组(Z=-5. 884 0～-3. 617 2,P均0. 05)。EOD组左侧楔前叶与左侧锯状回、左侧小脑IV-VI区、左侧小脑Crus2区的功能连接比LOD组高(Z=4. 087 7、3. 937 4、3. 672 1,P均0. 05);EOD组左侧楔前叶与右侧额中回、右侧眶额部额下回、右侧额上回的功能连接比LOD组低(Z=-4. 274 8、-3. 956 8、-4. 724 3、-3. 663 2,P均0. 05)。结论 DMN内部功能连接增高及额顶网络功能连接降低可能与EOD的发病机制相关,而DMN前部功能连接增高和后部功能连接降低可能与LOD的发病机制相关,不同发病年龄的成年抑郁症患者可能有不同的发病机制。     

Resting state brain network function in major depression – Depression symptomatology,antidepressant treatment effects,future research

The alterations of functional connectivity brain networks in major depressive disorder (MDD) have been subject of a large number of studies. Using different methodologies and focusing on diverse aspects of the disease, research shows heterogeneous results lacking integration. Disrupted network connectivity has been found in core MDD networks like the default mode network (DMN), the central executive network (CEN), and the salience network, but also in cerebellar and thalamic circuitries. Here we review literature published on resting state brain network function in MDD focusing on methodology, and clinical characteristics including symptomatology and antidepressant treatment related findings. There are relatively few investigations concerning the qualitative aspects of symptomatology of MDD, whereas most studies associate quantitative aspects with distinct resting state functional connectivity alterations. Such depression severity associated alterations are found in the DMN, frontal, cerebellar and thalamic brain regions as well as the insula and the subgenual anterior cingulate cortex. Similarly, different therapeutical options in MDD and their effects on brain function showed patchy results. Herein, pharmaceutical treatments reveal functional connectivity alterations throughout multiple brain regions notably the DMN, fronto-limbic, and parieto-temporal regions. Psychotherapeutical interventions show significant functional connectivity alterations in fronto-limbic networks, whereas electroconvulsive therapy and repetitive transcranial magnetic stimulation result in alterations of the subgenual anterior cingulate cortex, the DMN, the CEN and the dorsal lateral prefrontal cortex. While it appears clear that functional connectivity alterations are associated with the pathophysiology and treatment of MDD, future research should also generate a common strategy for data acquisition and analysis, as a least common denominator, to set the basis for comparability across studies and implementation of functional connectivity as a scientifically and clinically useful biomarker.