Abnormal characterization of dynamic functional connectivity in Alzheimer’s disease

Numerous studies have shown abnormal brain functional connectivity in individuals with Alzheimer’s disease(AD)or amnestic mild cognitive impairment(aMCI).However,most studies examined traditional resting state functional connections,ignoring the instantaneous connection mode of the whole brain.In this case-control study,we used a new method called dynamic functional connectivity(DFC)to look for abnormalities in patients with AD and aMCI.We calculated dynamic functional connectivity strength from functional magnetic resonance imaging data for each participant,and then used a support vector machine to classify AD patients and normal controls.Finally,we highlighted brain regions and brain networks that made the largest contributions to the classification.We found differences in dynamic function connectivity strength in the left precuneus,default mode network,and dorsal attention network among normal controls,aMCI patients,and AD patients.These abnormalities are potential imaging markers for the early diagnosis of AD.     

Ventral medial prefrontal functional connectivity and emotion regulation in chronic schizophrenia: A pilot study

People with schizophrenia exhibit impaired social cognitive functions, particularly emotion regulation. Abnormal activations of the ventral medial prefrontal cortex (vMPFC) during emotional tasks have been demonstrated in schizophrenia, suggesting its important role in emotion processing in patients. We used the resting-state functional connectivity approach, setting a functionally relevant region, the vMPFC, as a seed region to examine the intrinsic functional interactions and communication between the vMPFC and other brain regions in schizophrenic patients. We found hypo-connectivity between the vMPFC and the medial frontal cortex, right middle temporal lobe (MTL), right hippocampus, parahippocampal cortex (PHC) and amygdala. Further, there was a decreased strength of the negative connectivity (or anticorrelation) between the vMPFC and the bilateral dorsal lateral prefrontal cortex (DLPFC) and pre-supplementary motor areas. Among these connectivity alterations, reduced vMPFC-DLPFC connectivity was positively correlated with positive symptoms on the Positive and Negative Syndrome Scale, while vMPFC-right MTL/PHC/amygdala functional connectivity was positively correlated with the performance of emotional regulation in patients. These findings imply that communication and coordination throughout the brain networks are disrupted in schizophrenia. The emotional correlates of vMPFC connectivity suggest a role of the hypo-connectivity between these regions in the neuropathology of abnormal social cognition in chronic schizophrenia.     

Non-concomitant cortical structural and functional alterations in sensorimotor areas following incomplete spinal cord injury

Brain plasticity, including anatomical changes and functional reorganization, is the physiological basis of functional recovery after spinal cord injury(SCI). The correlation between brain anatomical changes and functional reorganization after SCI is unclear. This study aimed to explore whether alterations of cortical structure and network function are concomitant in sensorimotor areas after incomplete SCI. Eighteen patients with incomplete SCI(mean age 40.94 ± 14.10 years old; male:female, 7:11) and 18 healthy subjects(37.33 ± 11.79 years old; male:female, 7:11) were studied by resting state functional magnetic resonance imaging. Gray matter volume(GMV) and functional connectivity were used to evaluate cortical structure and network function, respectively. There was no significant alteration of GMV in sensorimotor areas in patients with incomplete SCI compared with healthy subjects. Intra-hemispheric functional connectivity between left primary somatosensory cortex(BA1) and left primary motor cortex(BA4), and left BA1 and left somatosensory association cortex(BA5) was decreased, as well as inter-hemispheric functional connectivity between left BA1 and right BA4, left BA1 and right BA5, and left BA4 and right BA5 in patients with SCI. Functional connectivity between both BA4 areas was also decreased. The decreased functional connectivity between the left BA1 and the right BA4 positively correlated with American Spinal Injury Association sensory score in SCI patients. The results indicate that alterations of cortical anatomical structure and network functional connectivity in sensorimotor areas were non-concomitant in patients with incomplete SCI, indicating the network functional changes in sensorimotor areas may not be dependent on anatomic structure. The strength of functional connectivity within sensorimotor areas could serve as a potential imaging biomarker for assessment and prediction of sensory function in patients with incomplete SCI. This trial was registered with the Chinese Clinical Trial Registry(registration number: Chi CTR-ROC-17013566).     

An abnormal resting-state functional brain network indicates progression towards Alzheimer＇s disease

Brain structure and cognitive function change in the temporal lobe,hippocampus,and prefrontal cortex of patients with mild cognitive impairment and Alzheimer’s disease,and brain network-connection strength,network efficiency,and nodal attributes are abnormal.However,existing research has only analyzed the differences between these patients and normal controls.In this study,we constructed brain networks using resting-state functional MRI data that was extracted from four populations(normal controls,patients with early mild cognitive impairment,patients with late mild cognitive impairment,and patients with Alzheimer’s disease)using the Alzheimer’s Disease Neuroimaging Initiative data set.The aim was to analyze the characteristics of resting-state functional neural networks,and to observe mild cognitive impairment at different stages before the transformation to Alzheimer’s disease.Results showed that as cognitive deficits increased across the four groups,the shortest path in the resting-state functional network gradually increased,while clustering coefficients gradually decreased.This evidence indicates that dementia is associated with a decline of brain network efficiency.In addition,the changes in functional networks revealed the progressive deterioration of network function across brain regions from healthy elderly adults to those with mild cognitive impairment and Alzheimer’s disease.The alterations of node attributes in brain regions may reflect the cognitive functions in brain regions,and we speculate that early impairments in memory,hearing,and language function can eventually lead to diffuse brain injury and other cognitive impairments.     

Altered electroencephalographic networks in developmental dyslexia after remedial training: a prospective case-control study

Electroencephalographic studies using graph theoretic analysis have found aberrations in functional connectivity in children with developmental dyslexia. However, how the training with visual tasks can change the functional connectivity of the semantic network in developmental dyslexia is still unclear. We looked for differences in local and global topological properties of functional networks between 21 healthy controls and 22 dyslexic children(8–9 years old) before and after training with visual tasks in this prospective case-control study. The minimum spanning tree method was used to construct the subjects' brain networks in multiple electroencephalographic frequency ranges during a visual word/pseudoword discrimination task. We found group differences in the theta, alpha, beta and gamma bands for four graph measures suggesting a more integrated network topology in dyslexics before the training compared to controls. After training, the network topology of dyslexic children had become more segregated and similar to that of the controls. In the θ, α and β1-frequency bands, compared to the controls, the pre-training dyslexics exhibited a reduced degree and betweenness centrality of the left anterior temporal and parietal regions. The simultaneous appearance in the left hemisphere of hubs in temporal and parietal(α, β1), temporal and superior frontal cortex(θ, α), parietal and occipitotemporal cortices(β1), identified in the networks of normally developing children was not present in the brain networks of dyslexics. After training, the hub distribution for dyslexics in the theta and beta1 bands had become similar to that of the controls. In summary, our findings point to a less efficient network configuration in dyslexics compared to a more optimal global organization in the controls. This is the first study to investigate the topological organization of functional brain networks of Bulgarian dyslexic children. Approval for the study was obtained from the Ethics Committee of the Institute of Neurobiology and the Institute for Population and Human Studies, Bulgarian Academy of Sciences(approval No. 02-41/12.07.2019) on March 28, 2017, and the State Logopedic Center and the Ministry of Education and Science(approval No. 09-69/14.03.2017) on July 12, 2019.     

Correlations between hippocampal functional connectivity,structural changes,and clinical data in patients with relapsing-remitting multiple sclerosis: a case-control study using multimodal magnetic resonance imaging

Multiple sclerosis is associated with structural and functional brain alterations leading to cognitive impairments across multiple domains including attention,memory,and the speed of information processing.The hippocampus,which is a brain important structure involved in memory,undergoes microstructural changes in the early stage of multiple sclerosis.In this study,we analyzed hippocampal function and structure in patients with relapsing-remitting multiple sclerosis and explored correlations between the functional connectivity of the hippocampus to the whole brain,changes in local brain function and microstructure,and cognitive function at rest.We retrospectively analyzed data from 20 relapsing-remitting multiple sclerosis patients admitted to the Department of Neurology at the China-Japan Union Hospital of Jilin University,China,from April 2015 to November 2019.Sixteen healthy volunteers were recruited as the healthy control group.All participants were evaluated using a scale of extended disability status and the Montreal cognitive assessment within 1 week before and after head diffusion tensor imaging and functional magnetic resonance imaging.Compared with the healthy control group,the patients with relapsing-remitting multiple sclerosis had lower Montreal cognitive assessment scores and regions of simultaneously enhanced and attenuated whole-brain functional connectivity and local functional connectivity in the bilateral hippocampus.Hippocampal diffusion tensor imaging data showed that,compared with the healthy control group,patients with relapsing-remitting multiple sclerosis had lower hippocampal fractional anisotropy values and higher mean diffusivity values,suggesting abnormal hippocampal structure.The left hippocampus whole-brain functional connectivity was negatively correlated with the Montreal cognitive assessment score(r=-0.698,P=0.025),and whole-brain functional connectivity of the right hippocampus was negatively correlated with extended disability status scale score(r=-0.649,P=0.042).The mean diffusivity value of the left hippocampus was negatively correlated with the Montreal cognitive assessment score(r=-0.729,P=0.017)and positively correlated with the extended disability status scale score(r=0.653,P=0.041).The right hippocampal mean diffusivity value was positively correlated with the extended disability status scale score(r=0.684,P=0.029).These data suggest that the functional connectivity and presence of structural abnormalities in the hippocampus in patients with relapse-remission multiple sclerosis are correlated with the degree of cognitive function and extent of disability.This study was approved by the Ethics Committee of China-Japan Union Hospital of Jilin University,China(approval No.201702202)on February 22,2017.     

Changes in brain functional network connectivity after stroke简

Studies have shown that functional network connection models can be used to study brain net- work changes in patients with schizophrenia. In this study, we inferred that these models could also be used to explore functional network connectivity changes in stroke patients. We used independent component analysis to find the motor areas of stroke patients, which is a novel way to determine these areas. In this study, we collected functional magnetic resonance imaging datasets from healthy controls and right-handed stroke patients following their first ever stroke. Using independent component analysis, six spatially independent components highly correlat- ed to the experimental paradigm were extracted. Then, the functional network connectivity of both patients and controls was established to observe the differences between them. The results showed that there were 11 connections in the model in the stroke patients, while there were only four connections in the healthy controls. Further analysis found that some damaged connections may be compensated for by new indirect connections or circuits produced after stroke. These connections may have a direct correlation with the degree of stroke rehabilitation. Our findings suggest that functional network connectivity in stroke patients is more complex than that in hea- lthy controls, and that there is a compensation loop in the functional network following stroke. This implies that functional network reorganization plays a very important role in the process of rehabilitation after stroke.     

Disrupted structural and functional brain connectomes in mild cognitive impairment and Alzheimer＇s disease

Alzheimer＇s disease （AD） is the most common type of dementia, comprising an estimated 60-80% of all dementia cases. It is clinically characterized by impairments of memory and other cognitive functions. Previous studies have demonstrated that these impairments are associated with abnormal structural and functional connections among brain regions, leading to a disconnection concept of AD. With the advent of a combination of non-invasive neuroimaging （structural magnetic resonance imaging （MRI）, diffusion MRI, and functional MRI） and neurophysiological techniques （electroencephalography and magnetoencephaJography） with graph theoretical analysis, recent studies have shown that patients with AD and mild cognitive impairment （MCI）, the prodromal stage of AD, exhibit disrupted topological organization in large-scale brain networks （i.e., connectomics） and that this disruption is significantly correlated with the decline of cognitive functions. In this review, we summarize the recent progress of brain connectomics in AD and MCI, focusing on the changes in the topological organization of large-scale structural and functional brain networks using graph theoretical approaches. Based on the two different perspectives of information segregation and integration, the literature reviewed here suggests that AD and MCI are associated with disrupted segregation and integration in brain networks. Thus, these connectomics studies open up a new window for understanding the pathophysiological mechanisms of AD and demonstrate the potential to uncover imaging biomarkers for clinical diagnosis and treatment evaluation for this disease.     

Resting-state functional connectivity abnormalities in first-onset unmedicated depression简

Depression is closely linked to the morphology and functional abnormalities of multiple brain regions; however, its topological structure throughout the whole brain remains unclear. We col- lected resting-state functional MRI data from 36 first-onset unmedicated depression patients and 27 healthy controls. The resting-state functional connectivity was constructed using the Auto- mated Anatomical Labeling template with a partial correlation method. The metrics calculation and statistical analysis were performed using complex network theory. The results showed that both depressive patients and healthy controls presented typical small-world attributes. Compared with healthy controls, characteristic path length was significantly shorter in depressive patients, suggesting development toward randomization. Patients with depression showed apparently abnormal node attributes at key areas in cortical-striatal-pallidal-thalamic circuits. In addition, right hippocampus and right thalamus were closely linked with the severity of depression. We se- lected 270 local attributes as the classification features and their P values were regarded as criteria for statistically significant differences. An artificial neural network algorithm was applied for classification research. The results showed that brain network metrics could be used as an effec- tive feature in machine learning research, which brings about a reasonable application prospect for brain network metrics. The present study also highlighted a significant positive correlation between the importance of the attributes and the intergroup differences; that is, the more sig- nificant the differences in node attributes, the stronger their contribution to the classification. Experimental findings indicate that statistical significance is an effective quantitative indicator of the selection of brain network metrics and can assist the clinical diagnosis of depression.     

Small-worldness of brain networks after brachial plexus injury: a resting-state functional magnetic resonance imaging study

Research on brain function after brachial plexus injury focuses on local cortical functional reorganization,and few studies have focused on brain networks after brachial plexus injury.Changes in brain networks may help understanding of brain plasticity at the global level.We hypothesized that topology of the global cerebral resting-state functional network changes after unilateral brachial plexus injury.Thus,in this cross-sectional study,we recruited eight male patients with unilateral brachial plexus injury(right handedness,mean age of 27.9±5.4years old)and eight male healthy controls(right handedness,mean age of 28.6±3.2).After acquiring and preprocessing resting-state magnetic resonance imaging data,the cerebrum was divided into 90 regions and Pearson’s correlation coefficient calculated between regions.These correlation matrices were then converted into a binary matrix with affixed sparsity values of 0.1–0.46.Under sparsity conditions,both groups satisfied this small-world property.The clustering coefficient was markedly lower,while average shortest path remarkably higher in patients compared with healthy controls.These findings confirm that cerebral functional networks in patients still show smallworld characteristics,which are highly effective in information transmission in the brain,as well as normal controls.Alternatively,varied small-worldness suggests that capacity of information transmission and integration in different brain regions in brachial plexus injury patients is damaged.     

Low-frequency rTMS induces modifications in cortical structural connectivity - functional connectivity coupling in schizophrenia patients with auditory verbal hallucinations

Auditory verbal hallucinations (AVH) are distinctive clinical manifestations of schizophrenia. While low-frequency repetitive transcranial magnetic stimulation (rTMS) has demonstrated potential in mitigating AVH, the precise mechanisms by which it operates remain obscure. This study aimed to investigate alternations in structural connectivity and functional connectivity (SC-FC) coupling among schizophrenia patients with AVH prior to and following treatment with 1 Hz rTMS that specifically targets the left temporoparietal junction. Initially, patients exhibited significantly reduced macroscopic whole brain level SC-FC coupling compared to healthy controls. Notably, SC-FC coupling increased significantly across multiple networks, including the somatomotor, dorsal attention, ventral attention, frontoparietal control, and default mode networks, following rTMS treatment. Significant alternations in SC-FC coupling were noted in critical nodes comprising the somatomotor network and the default mode network, such as the precentral gyrus and the ventromedial prefrontal cortex, respectively. The alternations in SC-FC coupling exhibited a correlation with the amelioration of clinical symptom. The results of our study illuminate the intricate relationship between white matter structures and neuronal activity in patients who are receiving low-frequency rTMS. This advances our understanding of the foundational mechanisms underlying rTMS treatment for AVH.     

Lifespan anxiety is reflected in human amygdala cortical connectivity

The amygdala plays a pivotal role in processing anxiety and connects to large‐scale brain networks. However, intrinsic functional connectivity (iFC) between amygdala and these networks has rarely been examined in relation to anxiety, especially across the lifespan. We employed resting‐state functional MRI data from 280 healthy adults (18–83.5 yrs) to elucidate the relationship between anxiety and amygdala iFC with common cortical networks including the visual network, somatomotor network, dorsal attention network, ventral attention network, limbic network, frontoparietal network, and default network. Global and network‐specific iFC were separately computed as mean iFC of amygdala with the entire cerebral cortex and each cortical network. We detected negative correlation between global positive amygdala iFC and trait anxiety. Network‐specific associations between amygdala iFC and anxiety were also detectable. Specifically, the higher iFC strength between the left amygdala and the limbic network predicted lower state anxiety. For the trait anxiety, left amygdala anxiety–connectivity correlation was observed in both somatomotor and dorsal attention networks, whereas the right amygdala anxiety–connectivity correlation was primarily distributed in the frontoparietal and ventral attention networks. Ventral attention network exhibited significant anxiety–gender interactions on its iFC with amygdala. Together with findings from additional vertex‐wise analysis, these data clearly indicated that both low‐level sensory networks and high‐level associative networks could contribute to detectable predictions of anxiety behaviors by their iFC profiles with the amygdala. This set of systems neuroscience findings could lead to novel functional network models on neural correlates of human anxiety and provide targets for novel treatment strategies on anxiety disorders. Hum Brain Mapp 37:1178–1193, 2016. © 2015 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc .     

Individual differences in sustained attention are associated with cortical thickness

Several studies have examined how individual differences in sustained attention relate to functional brain measures (e.g., functional connectivity), but far fewer studies relate sustained attention ability, or cognition in general, to individual differences in cortical structure. Functional magnetic resonance imaging meta‐analyses and patient work have highlighted that frontoparietal regions, lateralized to the right hemisphere, are critical for sustained attention, though recent work implicates a broader expanse of brain regions. The current study sought to determine if and where variation in cortical thickness is significantly associated with sustained attention performance. Sustained attention was measured using the gradual onset continuous performance task and the Test of Variables of Attention in 125 adult Veteran participants after acquiring two high‐resolution structural MRI scans. Whole‐brain vertex‐wise analyses of the cortex demonstrated that better sustained attention was associated with increased thickness in visual, somatomotor, frontal, and parietal cortices, especially in the right hemisphere. Network‐based analyses revealed relationships between sustained attention and cortical thickness in the dorsal attention, ventral attention, somatomotor, and visual networks. These results indicate cortical thickness in multiple regions and networks is associated with sustained attention, and add to the growing knowledge of how structural MRI can help explain individual differences in cognition.     

Mapping the functional and structural connectivity of the scene network

The recognition and perception of places has been linked to a network of scene-selective regions in the human brain. While previous studies have focussed on functional connectivity between scene-selective regions themselves, less is known about their connectivity with other cortical and subcortical regions in the brain. Here, we determine the functional and structural connectivity profile of the scene network. We used fMRI to examine functional connectivity between scene regions and across the whole brain during rest and movie-watching. Connectivity within the scene network revealed a bias between posterior and anterior scene regions implicated in perceptual and mnemonic aspects of scene perception respectively. Differences between posterior and anterior scene regions were also evident in the connectivity with cortical and subcortical regions across the brain. For example, the Occipital Place Area (OPA) and posterior Parahippocampal Place Area (PPA) showed greater connectivity with visual and dorsal attention networks, while anterior PPA and Retrosplenial Complex showed preferential connectivity with default mode and frontoparietal control networks and the hippocampus. We further measured the structural connectivity of the scene network using diffusion tractography. This indicated both similarities and differences with the functional connectivity, highlighting biases between posterior and anterior regions, but also between ventral and dorsal scene regions. Finally, we quantified the structural connectivity between the scene network and major white matter tracts throughout the brain. These findings provide a map of the functional and structural connectivity of scene-selective regions to each other and the rest of the brain.     

Altered attention networks in benign childhood epilepsy with centrotemporal spikes (BECTS): A resting-state fMRI study

It is noteworthy that some children with benign childhood epilepsy with centrotemporal spikes (BECTS) show attention problems despite their favorable seizure outcome. Resting-state functional magnetic resonance imaging (fMRI) is a method widely used to detect brain network alterations in neuropsychiatric diseases. We used resting-state functional magnetic resonance imaging (fMRI) to investigate specific brain networks related to attention deficit in children with BECTS. Resting-state fMRI was performed in patients with BECTS with ADHD (n = 15) and those with BECTS without ADHD (n = 15) and in healthy controls (n = 15). Unbiased seed-based whole-brain functional connectivity analysis was used to study the connectivity pattern of three resting-state networks, including the ventral attention network (VAN) and the dorsal attention network (DAN) and the default mode network (DMN). Patients with BECTS with ADHD displayed decreased functional connectivity in the DAN compared with other two groups, while patients with BECTS without ADHD showed increased functional connectivity in the DAN. Moreover, we found increased functional connectivity in the VAN and in the DMN in patients with BECTS with or without ADHD when comparing with controls. These results showed that the newly-diagnosed children with BECTS displayed brain activity alterations in the ventral and dorsal attention networks. The difference in the extent of impairment in the dorsal attention network of patients with BECTS with ADHD and patients with BECTS without ADHD may lead to improved understanding of the underlying neuropathophysiology and treatment of BECTS with ADHD and BECTS without ADHD.     

Local functional connectivity suggests functional immaturity in children with attention‐deficit/hyperactivity disorder

Previous studies have associated Attention‐Deficit/Hyperactivity Disorder (ADHD) with a maturational lag of brain functional networks. Functional connectivity of the human brain changes from primarily local to more distant connectivity patterns during typical development. Under the maturational lag hypothesis, we expect children with ADHD to exhibit increased local connectivity and decreased distant connectivity compared with neurotypically developing (ND) children. We applied a graph‐theory method to compute local and distant connectivity levels and cross‐sectionally compared them in a sample of 120 children with ADHD and 120 age‐matched ND children (age range = 7–17 years). In addition, we measured if potential group differences in local and distant connectivity were stable across the age range considered. Finally, we assessed the clinical relevance of observed group differences by correlating the connectivity levels and ADHD symptoms severity separately for each group. Children with ADHD exhibited more local connectivity than age‐matched ND children in multiple brain regions, mainly overlapping with default mode, fronto‐parietal and ventral attentional functional networks (p < .05‐ threshold free‐cluster enhancement–family‐wise error). We detected an atypical developmental pattern of local connectivity in somatomotor regions, that is, decreases with age in ND children, and increases with age in children with ADHD. Furthermore, local connectivity within somatomotor areas correlated positively with clinical severity of ADHD symptoms, both in ADHD and ND children. Results suggest an immature functional state of multiple brain networks in children with ADHD. Whereas the ADHD diagnosis is associated with the integrity of the system comprising the fronto‐parietal, default mode and ventral attentional networks, the severity of clinical symptoms is related to atypical functional connectivity within somatomotor areas. Additionally, our findings are in line with the view of ADHD as a disorder of deviated maturational trajectories, mainly affecting somatomotor areas, rather than delays that normalize with age.     

Distinct brain structural‐functional network topological coupling explains different outcomes in tinnitus patients treated with sound therapy

Topological properties, which serve as the core of the neural network, and their couplings can reflect different therapeutic effects in tinnitus patients. We hypothesized that tinnitus patients with different outcomes after sound therapy (narrowband noise) would have distinct brain network topological alterations. Diffusion tensor imaging and resting‐state functional magnetic resonance imaging (fMRI) were prospectively performed in 60 patients with idiopathic tinnitus and 57 healthy controls (HCs). Graph‐theoretical network analyses of structural connectivity (SC), functional connectivity (FC), and SC and FC coupling were performed. Associations between clinical performance and graph‐theoretical features were also analyzed. Treatment was effective (effective group; EG) in 28 patients and ineffective (ineffective group; IG) in 32 patients. For FC, the patients in the EG showed higher local efficiency than patients in the IG. For SC, patients in both the EG and IG displayed lower normalized characteristic path length, characteristic path length, and global efficiency than the HCs. More importantly, patients in the IG had higher coupling than the HCs, whereas there was no difference in coupling between patients in the EG and HCs. Additionally, there were significant associations between the SC features and clinical performance in patients in the EG. Our findings demonstrate that tinnitus patients exhibited significant brain network topological alterations, especially in the structural brain network. More importantly, patients who demonstrated different curative effects showed distinct SC‐FC topological coupling properties. SC‐FC coupling could be an indicator that could be used to predict prognoses in patients with idiopathic tinnitus before sound therapy.     

Characterizing the impact of adversity,abuse, and neglect on adolescent amygdala resting-state functional connectivity

Characterizing typologies of childhood adversity may inform the development of risk profiles and corresponding interventions aimed at mitigating its lifelong consequences. A neurobiological grounding of these typologies requires systematic comparisons of neural structure and function among individuals with different exposure histories. Using seed-to-whole brain analyses, this study examined associations between childhood adversity and amygdala resting-state functional connectivity (rs-fc) in adolescents aged 11–19 years across three independent studies (N = 223; 127 adversity group) in both general and dimensional models of adversity (comparing abuse and neglect). In a general model, adversity was associated with altered amygdala rs-fc with clusters within the left anterior lateral prefrontal cortex. In a dimensional model, abuse was associated with altered amygdala rs-fc within the orbitofrontal cortex, dorsal precuneus, posterior cingulate cortex, and dorsal anterior cingulate cortex/anterior mid-cingulate cortex, as well as within the dorsal attention, visual, and somatomotor networks. Neglect was associated with altered amygdala rs-fc with the hippocampus, supplementary motor cortex, temporoparietal junction, and regions within the dorsal attention network. Both general and dimensional models revealed unique regions, potentially reflecting pathways by which distinct histories of adversity may influence adolescent behavior, cognition, and psychopathology.     

Functional resting-state networks are differentially affected in schizophrenia

Neurobiological theories posit that schizophrenia relates to disturbances in connectivity between brain regions. Resting-state functional magnetic resonance imaging is a powerful tool for examining functional connectivity and has revealed several canonical brain networks, including the default mode, dorsal attention, executive control, and salience networks. The purpose of this study was to examine changes in these networks in schizophrenia. 42 patients with schizophrenia and 61 healthy subjects completed a RS-fMRI scanning session. Seed-based region-of-interest correlation analysis was used to identify the default mode, dorsal attention, executive control, and salience networks. Compared to healthy subjects, individuals with schizophrenia demonstrated greater connectivity between the posterior cingulate cortex, a key hub of the default mode, and the left inferior gyrus, left middle frontal gyrus, and left middle temporal gyrus. Interestingly, these regions were more strongly connected to the executive control network in healthy control subjects. In contrast to the default mode, patients demonstrated less connectivity in the executive control and dorsal attention networks. No differences were observed in the salience network. The results indicate that resting-state networks are differentially affected in schizophrenia. The alterations are characterized by reduced segregation between the default mode and executive control networks in the prefrontal cortex and temporal lobe, and reduced connectivity in the dorsal attention and executive control networks. The changes suggest that the process of functional specialization is altered in schizophrenia. Further work is needed to determine if the alterations are related to disturbances in white matter connectivity, neurodevelopmental abnormalities, and genetic risk for schizophrenia.     

Topological organization of the human brain functional connectome across the lifespan

Human brain function undergoes complex transformations across the lifespan. We employed resting-state functional MRI and graph-theory approaches to systematically chart the lifespan trajectory of the topological organization of human whole-brain functional networks in 126 healthy individuals ranging in age from 7 to 85 years. Brain networks were constructed by computing Pearson's correlations in blood-oxygenation-level-dependent temporal fluctuations among 1024 parcellation units followed by graph-based network analyses. We observed that the human brain functional connectome exhibited highly preserved non-random modular and rich club organization over the entire age range studied. Further quantitative analyses revealed linear decreases in modularity and inverted-U shaped trajectories of local efficiency and rich club architecture. Regionally heterogeneous age effects were mainly located in several hubs (e.g., default network, dorsal attention regions). Finally, we observed inverse trajectories of long- and short-distance functional connections, indicating that the reorganization of connectivity concentrates and distributes the brain's functional networks. Our results demonstrate topological changes in the whole-brain functional connectome across nearly the entire human lifespan, providing insights into the neural substrates underlying individual variations in behavior and cognition. These results have important implications for disease connectomics because they provide a baseline for evaluating network impairments in age-related neuropsychiatric disorders.