Decreased resting-state interhemispheric functional connectivity in unaffected siblings of schizophrenia patients

BackgroundNeuroimaging studies in unaffected siblings of schizophrenia patients can provide clues to the pathophysiology for the development of schizophrenia. However, little is known about the alterations of the interhemispheric resting-state functional connectivity (FC) in siblings, although the dysconnectivity hypothesis is prevailing in schizophrenia for years. In the present study, we used a newly validated voxel-mirrored homotopic connectivity (VMHC) method to identify whether aberrant interhemispheric FC was present in unaffected siblings at increased risk of developing schizophrenia at rest.MethodsForty-six unaffected siblings of schizophrenia patients and 50 age-, sex-, and education-matched healthy controls underwent a resting-state functional magnetic resonance imaging (fMRI). Automated VMHC was used to analyze the data.ResultsThe sibling group had lower VMHC than the control group in the angular gyrus (AG) and the lingual gyrus/cerebellum lobule VI. No region exhibited higher VMHC in the sibling group than in the control group. There was no significant sex difference of the VMHC values between male siblings and female siblings or between male controls and female controls, although evidence has been accumulated that size and shape of the corpus callosum, and functional homotopy differ between men and women.ConclusionsOur results first suggest that interhemispheric resting-state FC of VMHC is disrupted in unaffected siblings of schizophrenia patients, and add a new clue of abnormal interhemispheric resting-state FC to the pathophysiology for the development of schizophrenia.     

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。     

Abnormal Causal Connectivity by Structural Deficits in First-Episode,Drug-Naive Schizophrenia at Rest

Anatomical deficits and resting-state functional connectivity (FC) alterations in prefrontal-thalamic-cerebellar circuit have been implicated in the neurobiology of schizophrenia. However, the effect of structural deficits in schizophrenia on causal connectivity of this circuit remains unclear. This study was conducted to examine the causal connectivity biased by structural deficits in first-episode, drug-naive schizophrenia patients. Structural and resting-state functional magnetic resonance imaging (fMRI) data were obtained from 49 first-episode, drug-naive schizophrenia patients and 50 healthy controls. Data were analyzed by voxel-based morphometry and Granger causality analysis. The causal connectivity of the integrated prefrontal-thalamic (limbic)-cerebellar (sensorimotor) circuit was partly affected by structural deficits in first-episode, drug-naive schizophrenia as follows: (1) unilateral prefrontal-sensorimotor connectivity abnormalities (increased driving effect from the left medial prefrontal cortex [MPFC] to the sensorimotor regions); (2) bilateral limbic-sensorimotor connectivity abnormalities (increased driving effect from the right anterior cingulate cortex [ACC] to the sensorimotor regions and decreased feedback from the sensorimotor regions to the right ACC); and (3) bilateral increased and decreased causal connectivities among the sensorimotor regions. Some correlations between the gray matter volume of the seeds, along with their causal effects and clinical variables (duration of untreated psychosis and symptom severity), were also observed in the patients. The findings indicated the partial effects of structural deficits in first-episode, drug-naive schizophrenia on the prefrontal-thalamic (limbic)-cerebellar (sensorimotor) circuit. Schizophrenia may reinforce the driving connectivities from the left MPFC or right ACC to the sensorimotor regions and may disrupt bilateral causal connectivities among the sensorimotor regions.Key words: first-episode schizophrenia, causal effect, structural deficits, voxel-based morphometry, Granger causality analysis     

Intrinsic brain abnormalities in irritable bowel syndrome and effect of anxiety and depression

This resting-state functional magnetic resonance imaging (rs-fMRI) study investigated intrinsic brain abnormalities in irritable bowel syndrome (IBS) and effect of anxiety and depression. Thirty IBS patients and 31 matched healthy controls underwent rs-fMRI scanning. Regional brain activity was evaluated by measuring the amplitude of low-frequency fluctuation (ALFF) and compared between IBS patients and healthy controls with a two-sample t-test. Areas with abnormal ALFF were further used as seeds in subsequent inter-regional functional connectivity (FC) analysis. Statistical analyses were also performed by including anxiety and depression as covariates to evaluate their effect. Compared to healthy controls, IBS patients showed decreased ALFF in several core default mode network regions (medial prefrontal cortex [MPFC], posterior cingulate cortex [PCC], bilateral inferior parietal cortices [IPC]), and in middle frontal cortex, right orbital part of the superior frontal gyrus (ORBsup), dorsal anterior cingulate cortex (dACC), and ventral anterior cingulated cortex (vACC), while they showed increased ALFF in bilateral posterior insula and cuneus. In addition, IBS patients revealed decreased inter-regional positive FC between MPFC and right ORBsup, between vACC and PCC, as well as decreased negative FC between MPFC and left posterior insula, while they showed increased negative FC between MPFC and cuneus. The inclusion of anxiety and depression as covariates abolished ALFF differences in dACC and vACC, but none of the FC differences. In conclusion: IBS patients had disturbed intrinsic brain function. High levels of anxiety and depression in IBS patients could account for their decreased intrinsic brain activity in regions (the ACC) involved in affective processing.     

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.     

Reduction in gray matter of cerebellum in schizophrenia and its influence on static and dynamic connectivity

Pathophysiological and atrophic changes in the cerebellum have been well‐documented in schizophrenia. Reduction of gray matter (GM) in the cerebellum was confirmed across cognitive and motor cerebellar modules in schizophrenia. Such abnormalities in the cerebellum could potentially have widespread effects on both sensorimotor and cognitive symptoms. In this study, we investigated how reduction change in the cerebellum affects the static and the dynamic functional connectivity (FC) between the cerebellum and cortical/subcortical networks in schizophrenia. Reduction of GM in the cerebellum was confirmed across the cognitive and motor cerebellar modules in schizophrenic subjects. Results from this study demonstrates that the extent of reduction of GM within cerebellum correlated with increased static FCs between the cerebellum and the cortical/subcortical networks, including frontoparietal network (FPN), and thalamus in patients with schizophrenia. Decreased GM in the cerebellum was also associated with a declined dynamic FC between the cerebellum and the FPN in schizophrenic subjects. The severity of patients' positive symptom was related to these structural‐functional coupling score of cerebellum. These findings identified potential cerebellar driven functional changes associated with positive symptom deficits. A post hoc analysis exploring the effect of changed FC within cerebellum, confirmed that a significant positive relationship, between dynamic FCs of cerebellum–thalamus and intracerebellum existed in patients, but not in controls. The reduction of GM within the cerebellum might be associated with modulation of cerebellum–thalamus, and contributes to the dysfunctional cerebellar‐cortical communication in schizophrenia. Our results provide a new insight into the role of cerebellum in understanding the pathophysiological of schizophrenia.     

Schizophrenic Patients and Their Unaffected Siblings Share Increased Resting-State Connectivity in the Task-Negative Network but Not Its Anticorrelated Task-Positive Network

Background:

Abnormal connectivity of the anticorrelated intrinsic networks, the task-negative network (TNN), and the task-positive network (TPN) is implicated in schizophrenia. Comparisons between schizophrenic patients and their unaffected siblings enable further understanding of illness susceptibility and pathophysiology. We examined the resting-state connectivity differences in the intrinsic networks between schizophrenic patients, their unaffected siblings, and healthy controls.

Methods:

Resting-state functional magnetic resonance images were obtained from 25 individuals in each subject group. The posterior cingulate cortex/precuneus and right dorsolateral prefrontal cortex were used as seed regions to identify the TNN and TPN through functional connectivity analysis. Interregional connectivity strengths were analyzed using overlapped intrinsic networks composed of regions common to all subject groups.

Results:

Schizophrenic patients and their unaffected siblings showed increased connectivity in the TNN between the bilateral inferior temporal gyri. By contrast, schizophrenic patients alone demonstrated increased connectivity between the posterior cingulate cortex/precuneus and left inferior temporal gyrus and between the ventral medial prefrontal cortex and right lateral parietal cortex in the TNN. Schizophrenic patients exhibited increased connectivity between the left dorsolateral prefrontal cortex and right inferior frontal gyrus in the TPN relative to their unaffected siblings, though this trend only approached statistical significance in comparison to healthy controls.

Conclusion:

Resting-state hyperconnectivity of the intrinsic networks may disrupt network coordination and thereby contribute to the pathophysiology of schizophrenia. Similar, though milder, hyperconnectivity of the TNN in unaffected siblings of schizophrenic patients may contribute to the identification of schizophrenia endophenotypes and ultimately to the determination of schizophrenia risk genes.     

Altered cerebro-cerebellum resting-state functional connectivity in HIV-infected male patients

In addition to the role of planning and executing movement, the cerebellum greatly contributes to cognitive process. Numerous studies have reported structural and functional abnormalities in the cerebellum for HIV-infected patients, but little is known about the altered functional connectivity of particular cerebellar subregions and the cerebrum. Therefore, this study aimed to explore the resting-state functional connectivity (rsFC) changes of the cerebellum and further analyze the relationship between the rsFC changes and the neuropsychological evaluation. The experiment involved 26 HIV-infected men with asymptomatic neurocognitive impairment (ANI) and 28 healthy controls (HC). We selected bilateral hemispheric lobule VI and lobule IX as seed regions and mapped the whole-brain rsFC for each subregion. Results revealed that right lobule VI showed significant increased rsFC with the anterior cingulate cortex (ACC) in HIV-infected subjects. In addition, the correlation analysis on HIV-infected subjects illustrated the increased rsFC was negatively correlated with the attention/working memory score. Moreover, significantly increased cerebellar rsFCs were also observed in HIV-infected patients related to right inferior frontal gyrus (IFG) and right superior medial gyrus (SMG) while decreased rsFC was just found between right lobule VI and the left hippocampus (HIP). These findings suggested that, abnormalities of cerebro-cerebellar functional connectivity might be associated with cognitive dysfunction in HIV-infected men, particularly working memory impairment. It could also be the underlying mechanism of ANI, providing further evidence for early injury in the neural substrate of HIV-infected patients.     

Prefrontal Brain Network Connectivity Indicates Degree of Both Schizophrenia Risk and Cognitive Dysfunction

Objective:

Cognitive dysfunction is a core feature of schizophrenia, and persons at risk for schizophrenia may show subtle deficits in attention and working memory. In this study, we investigated the relationship between integrity of functional brain networks and performance in attention and working memory tasks as well as schizophrenia risk.

Methods:

A total of 235 adults representing 3 levels of risk (102 outpatients with schizophrenia, 70 unaffected first-degree relatives of persons with schizophrenia, and 63 unrelated healthy controls [HCs]) completed resting-state functional magnetic resonance imaging and a battery of attention and working memory tasks (Brief Test of Attention, Hopkins Verbal Learning Test, and Brief Visuospatial Memory Test) on the same day. Functional networks were defined based on coupling with seeds in the dorsal anterior cingulate cortex, dorsolateral prefrontal cortex (DLPFC), medial prefrontal cortex (MPFC), and primary visual cortex. Networks were then dissected into regional clusters of connectivity that were used to generate individual interaction matrices representing functional connectivity within each network.

Results:

Both patients with schizophrenia and their first-degree relatives showed cognitive dysfunction compared with HCs. First canonicals indicated an inverse relationship between cognitive performance and connectivity within the DLPFC and MPFC networks. Multivariate analysis of variance revealed multivariate main effects of higher schizophrenia risk status on increased connectivity within the DLPFC and MPFC networks.

Conclusions:

These data suggest that excessive connectivity within brain networks coupled to the DLPFC and MPFC, respectively, accompany cognitive deficits in persons at risk for schizophrenia. This might reflect compensatory reactions in neural systems required for cognitive processing of attention and working memory tasks to brain changes associated with schizophrenia.Key words: resting state, fMRI, default-mode network, attention, working memory     

Alterations of voxel‐wise spontaneous activity and corresponding brain functional networks in multiple system atrophy patients with mild cognitive impairment

Emerging evidence has indicated that cognitive impairment is an underrecognized feature of multiple system atrophy (MSA). Mild cognitive impairment (MCI) is related to a high risk of dementia. However, the mechanism underlying MCI in MSA remains controversial. In this study, we conducted the amplitude of low‐frequency fluctuation (ALFF) and seed‐based functional connectivity (FC) analyses to detect the characteristics of local neural activity and corresponding network alterations in MSA patients with MCI (MSA‐MCI). We enrolled 80 probable MSA patients classified as cognitively normal (MSA‐NC, n = 36) and MSA‐MCI (n = 44) and 40 healthy controls. Compared with MSA‐NC, MSA‐MCI exhibited decreased ALFF in the right dorsal lateral prefrontal cortex (RDLPFC) and increased ALFF in the right cerebellar lobule IX and lobule IV–V. In the secondary FC analyses, decreased FC in the left inferior parietal lobe (IPL) was observed when we set the RDLPFC as the seed region. Decreased FC in the bilateral cuneus, left precuneus, and left IPL and increased FC in the right middle temporal gyrus were shown when we set the right cerebellar lobule IX as the seed region. Furthermore, FC of DLPFC‐IPL and cerebello‐cerebral circuit, as well as ALFF alterations, were significantly correlated with Montreal Cognitive Assessment scores in MSA patients. We also employed whole‐brain voxel‐based morphometry analysis, but no gray matter atrophy was detected between the patient subgroups. Our findings indicate that altered spontaneous activity in the DLPFC and the cerebellum and disrupted DLPFC‐IPL, cerebello‐cerebral networks are possible biomarkers of early cognitive decline in MSA patients.     

Default mode network connectivity and reciprocal social behavior in 22q11.2 deletion syndrome

22q11.2 deletion syndrome (22q11DS) is a genetic mutation associated with disorders of cortical connectivity and social dysfunction. However, little is known about the functional connectivity (FC) of the resting brain in 22q11DS and its relationship with social behavior. A seed-based analysis of resting-state functional magnetic resonance imaging data was used to investigate FC associated with the posterior cingulate cortex (PCC), in (26) youth with 22qDS and (51) demographically matched controls. Subsequently, the relationship between PCC connectivity and Social Responsiveness Scale (SRS) scores was examined in 22q11DS participants. Relative to 22q11DS participants, controls showed significantly stronger FC between the PCC and other default mode network (DMN) nodes, including the precuneus, precentral gyrus and left frontal pole. 22q11DS patients did not show age-associated FC changes observed in typically developing controls. Increased connectivity between PCC, medial prefrontal regions and the anterior cingulate cortex, was associated with lower SRS scores (i.e. improved social competence) in 22q11DS. DMN integrity may play a key role in social information processing. We observed disrupted DMN connectivity in 22q11DS, paralleling reports from idiopathic autism and schizophrenia. Increased strength of long-range DMN connectivity was associated with improved social functioning in 22q11DS. These findings support a ‘developmental-disconnection’ hypothesis of symptom development in this disorder.     

Default-mode network connectivity in cognitively unimpaired drug-naïve patients with rigidity-dominant Parkinson’s disease

Parkinson’s disease (PD) with akinetic rigidity (PD_AR) is more likely to develop cognitive deficits compared to PD with tremor-dominant symptoms (PD_TD). The default mode network (DMN) is highly relevant for cognitive processes, so this study tested the functional connectivity (FC) of DMN in cognitively unimpaired PD_AR patients. Resting-state fMRI data were collected in 21 cognitively unimpaired early stage drug-naïve patients with PD_AR and 21 healthy controls (HC). PD patients were matched closely to HCs for demographic and cognitive variables. FC of DMN was evaluated by seed-based correlation approach. Compared to HCs, despite comparable cognitive performance and no statistically discernible GM volume differences, a disruption in the DMN of PD_AR subjects was detected. A decreased FC of DMN was found, specifically prominent in the posterior DMN. We also found a significantly increased FC of the anterior DMN. Three parts of left medial prefrontal regions (anterior, ventral, and dorsal) had significantly increased FC with the cerebellum. In addition, increased FC values of the anterior and ventral parts were negatively correlated with cognitive scores. An evident decline of FC of posterior DMN and enhanced compensatory FC of anterior DMN suggested an early functional disruption of DMN in PD_AR prior to clinical evidence of cognitive impairment. It could be hypothesized that the dysfunction of DMN connectivity may have a role in the development of cognitive decline in PD. However, further longitudinal studies are warranted to understand the underlying neural mechanisms and their relevance to clinical and cognitive outcomes in PD_AR subtype.     

Increased Cognition Connectivity Network in Major Depression Disorder: A fMRI Study

ObjectiveEvidence of the brain network involved in cognitive dysfunction has been inconsistent for major depressive disorder (MDD), especially during early stage of MDD. This study seeks to examine abnormal cognition connectivity network (CCN) in MDD within the whole brain.MethodsSixteen patients with MDD and 16 health controls were scanned during resting-state using 3.0 T functional magnetic resonance imaging (fMRI). All patients were first episode without any history of antidepressant treatment. Both the left and right dorsolateral prefrontal cortex (DLPFC) were used as individual seeds to identify CCN by the seed-target correlation analysis. Two sample t test was used to calculate between-group differences in CCN using fisher z-transformed correlation maps.ResultsThe CCN was constructed by bilateral seed DLPFC in two groups separately. Depressed subjects exhibited significantly increased functional connectivity (FC) by left DLPFC in one cluster, overlapping middle frontal gyrus, BA7, BA43, precuneus, BA6, BA40, superior temporal gyrus, BA22, inferior parietal lobule, precentral gyrus, BA4 and cingulate gyrus in left cerebrum. Health controls did not show any cluster with significantly greater FC compared to depressed subjects in left DLPFC network. There was no significant difference of FC in right DLPFC network between depressed subjects and the health controls.ConclusionThere are differences in CCN during early stage of MDD, as identified by increased FCs among part of frontal gyrus, parietal cortex, cingulate cortex, and BA43, BA22, BA4 with left DLPFC. These brain areas might be involved in the underlying mechanisms of cognitive dysfunction in MDD.     

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.     

Altered functional organization within and between resting-state networks in chronic subcortical infarction

This study aimed to investigate the changes in functional connectivity (FC) within each resting-state network (RSN) and between RSNs in subcortical stroke patients who were well recovered in global motor function. Eleven meaningful RSNs were identified via functional magnetic resonance imaging data from 25 subcortical stroke patients and 22 normal controls using independent component analysis. Compared with normal controls, stroke patients exhibited increased intranetwork FC in the sensorimotor (SMN), visual (VN), auditory (AN), dorsal attention (DAN), and default mode (DMN) networks; they also exhibited decreased intranetwork FC in the frontoparietal network (FPN) and anterior DMN. Stroke patients displayed a shift from no FC in controls to negative internetwork FC between the VN and AN as well as between the VN and SMN. Stroke patients also exhibited weakened positive (anterior and posterior DMN; posterior DMN and right FPN) or negative (AN and right FPN; posterior DMN and dorsal SMN) internetwork FC when compared with normal controls. We suggest that subcortical stroke may induce connectivity changes in multiple functional networks, affecting not only the intranetwork FC within RSNs but also the internetwork FC between these RSNs.     

Altered default mode network connectivity in Alzheimer's disease--a resting functional MRI and Bayesian network study

A number of functional magnetic resonance imaging (fMRI) studies reported the existence of default mode network (DMN) and its disruption due to the presence of a disease such as Alzheimer's disease (AD). In this investigation, first, we used the independent component analysis (ICA) technique to confirm the DMN difference between patients with AD and normal control (NC) reported in previous studies. Consistent with the previous studies, the decreased resting-state functional connectivity of DMN in AD was identified in posterior cingulated cortex (PCC), medial prefrontal cortex (MPFC), inferior parietal cortex (IPC), inferior temporal cortex (ITC), and hippocampus (HC). Moreover, we introduced Bayesian network (BN) to study the effective connectivity of DMN and the difference between AD and NC. When compared the DMN effective connectivity in AD with the one in NC using a nonparametric random permutation test, we found that connections from left HC to left IPC, left ITC to right HC, right HC to left IPC, to MPFC and to PCC were all lost. In addition, in AD group, the connection directions between right HC and left HC, between left HC and left ITC, and between right IPC and right ITC were opposite to those in NC group. The connections of right HC to other regions, except left HC, within the BN were all statistically in-distinguishable from 0, suggesting an increased right hippocampal pathological and functional burden in AD. The altered effective connectivity in patients with AD may reveal more characteristics of the disease and may serve as a potential biomarker.     

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 .     

Cerebellar development in childhood onset schizophrenia and non-psychotic siblings

We explored regional and total volumetric cerebellar differences in probands and their unaffected full siblings relative to typically developing participants. Participants included 94 (51 males) patients diagnosed with childhood onset schizophrenia (COS), 80 related non-psychotic siblings (37 males) and 110 (64 males) typically developing participants scanned longitudinally. The sample mean age was 16.87(S.D. = 4.7; range 6.5 to 29). We performed mixed model regressions to examine group differences in trajectory and volume. The COS group had smaller bilateral anterior lobes and anterior and total vermis volumes than controls. The COS group diverged from controls over time in total, left, right, and bilateral posterior inferior cerebellum. Siblings did not have any fixed volumetric differences relative to controls but differed from controls in developmental trajectories of total and right cerebellum, left inferior posterior, left superior posterior, and superior vermis. Results are consistent with previous COS findings and several reports of decreased cerebellar volume in adult onset schizophrenia. Sibling trajectories may represent a trait marker, although the effect size for volumetric differences in early adulthood may be small.     

Altered intra‐ and inter‐network functional coupling of resting‐state networks associated with motor dysfunction in stroke

Motor functions are supported through functional integration across the extended motor system network. Individuals following stroke often show deficits on motor performance requiring coordination of multiple brain networks; however, the assessment of connectivity patterns after stroke was still unclear. This study aimed to investigate the changes in intra‐ and inter‐network functional connectivity (FC) of multiple networks following stroke and further correlate FC with motor performance. Thirty‐three left subcortical chronic stroke patients and 34 healthy controls underwent resting‐state functional magnetic resonance imaging. Eleven resting‐state networks were identified via independent component analysis (ICA). Compared with healthy controls, the stroke group showed abnormal FC within the motor network (MN), visual network (VN), dorsal attention network (DAN), and executive control network (ECN). Additionally, the FC values of the ipsilesional inferior parietal lobule (IPL) within the ECN were negatively correlated with the Fugl‐Meyer Assessment (FMA) scores (hand + wrist). With respect to inter‐network interactions, the ipsilesional frontoparietal network (FPN) decreased FC with the MN and DAN; the contralesional FPN decreased FC with the ECN, but it increased FC with the default mode network (DMN); and the posterior DMN decreased FC with the VN. In sum, this study demonstrated the coexistence of intra‐ and inter‐network alterations associated with motor‐visual attention and high‐order cognitive control function in chronic stroke, which might provide insights into brain network plasticity following stroke.