The development of brain functional connectivity networks revealed by resting-state functional magnetic resonance imaging

Previous studies on brain functional connectivity networks in children have mainly focused on changes in function in specific brain regions, as opposed to whole brain connectivity in healthy children. By analyzing the independent components of activation and network connectivity between brain regions, we examined brain activity status and development trends in children aged 3 and 5 years. These data could provide a reference for brain function rehabilitation in children with illness or abnormal function. We acquired functional magnetic resonance images from 15 3-year-old children and 15 5-year-old children under natural sleep conditions. The participants were recruited from five kindergartens in the Nanshan District of Shenzhen City, China. The parents of the participants signed an informed consent form with the premise that they had been fully informed regarding the experimental protocol. We used masked independent component analysis and BrainNet Viewer software to explore the independent components of the brain and correlation connections between brain regions. We identified seven independent components in the two groups of children, including the executive control network, the dorsal attention network, the default mode network, the left frontoparietal network, the right frontoparietal network, the salience network, and the motor network. In the default mode network, the posterior cingulate cortex, medial frontal gyrus, and inferior parietal lobule were activated in both 3-and 5-year-old children, supporting the "three-brain region theory" of the default mode network. In the frontoparietal network, the frontal and parietal gyri were activated in the two groups of children, and functional connectivity was strengthened in 5-year-olds compared with 3-year-olds, although the nodes and network connections were not yet mature. The high-correlation network connections in the default mode networks and dorsal attention networks had been significantly strengthened in 5-year-olds vs. 3-year-olds. Further, the salience network in the 3-year-old children included an activated insula/inferior frontal gyrus-anterior cingulate cortex network circuit and an activated thalamus-parahippocampal-posterior cingulate cortex-subcortical regions network circuit. By the age of 5 years, nodes and high-correlation network connections(edges) were reduced in the salience network. Overall, activation of the dorsal attention network, default mode network, left frontoparietal network, and right frontoparietal network increased(the volume of activation increased, the signals strengthened, and the high-correlation connections increased and strengthened) in 5-year-olds compared with 3-year-olds, but activation in some brain nodes weakened or disappeared in the salience network, and the network connections(edges) were reduced. Between the ages of 3 and 5 years, we observed a tendency for function in some brain regions to be strengthened and for the generalization of activation to be reduced, indicating that specialization begins to develop at this time. The study protocol was approved by the local ethics committee of the Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences in China with approval No. SIAT-IRB-131115-H0075 on November 15, 2013.     

Altered functional connectivity in early Alzheimer's disease: a resting-state fMRI study

Previous studies have led to the proposal that patients with Alzheimer's disease (AD) may have disturbed functional connectivity between different brain regions. Furthermore, recent resting-state functional magnetic resonance imaging (fMRI) studies have also shown that low-frequency (<0.08 Hz) fluctuations (LFF) of the blood oxygenation level-dependent signals were abnormal in several brain areas of AD patients. However, few studies have investigated disturbed LFF connectivity in AD patients. By using resting-state fMRI, this study sought to investigate the abnormal functional connectivities throughout the entire brain of early AD patients, and analyze the global distribution of these abnormalities. For this purpose, the authors divided the whole brain into 116 regions and identified abnormal connectivities by comparing the correlation coefficients of each pair. Compared with healthy controls, AD patients had decreased positive correlations between the prefrontal and parietal lobes, but increased positive correlations within the prefrontal lobe, parietal lobe, and occipital lobe. The AD patients also had decreased negative correlations (closer to zero) between two intrinsically anti-correlated networks that had previously been found in the resting brain. By using resting-state fMRI, our results supported previous studies that have reported an anterior-posterior disconnection phenomenon and increased within-lobe functional connectivity in AD patients. In addition, the results also suggest that AD may disturb the correlation/anti-correlation effect in the two intrinsically anti-correlated networks.     

Extraction of dynamic functional connectivity from brain grey matter and white matter for MCI classification

Brain functional connectivity (FC) extracted from resting‐state fMRI (RS‐fMRI) has become a popular approach for diagnosing various neurodegenerative diseases, including Alzheimer's disease (AD) and its prodromal stage, mild cognitive impairment (MCI). Current studies mainly construct the FC networks between grey matter (GM) regions of the brain based on temporal co‐variations of the blood oxygenation level‐dependent (BOLD) signals, which reflects the synchronized neural activities. However, it was rarely investigated whether the FC detected within the white matter (WM) could provide useful information for diagnosis. Motivated by the recently proposed functional correlation tensors (FCT) computed from RS‐fMRI and used to characterize the structured pattern of local FC in the WM, we propose in this article a novel MCI classification method based on the information conveyed by both the FC between the GM regions and that within the WM regions. Specifically, in the WM, the tensor‐based metrics (e.g., fractional anisotropy [FA], similar to the metric calculated based on diffusion tensor imaging [DTI]) are first calculated based on the FCT and then summarized along each of the major WM fiber tracts connecting each pair of the brain GM regions. This could capture the functional information in the WM, in a similar network structure as the FC network constructed for the GM, based only on the same RS‐fMRI data. Moreover, a sliding window approach is further used to partition the voxel‐wise BOLD signal into multiple short overlapping segments. Then, both the FC and FCT between each pair of the brain regions can be calculated based on the BOLD signal segments in the GM and WM, respectively. In such a way, our method can generate dynamic FC and dynamic FCT to better capture functional information in both GM and WM and further integrate them together by using our developed feature extraction, selection, and ensemble learning algorithms. The experimental results verify that the dynamic FCT can provide valuable functional information in the WM; by combining it with the dynamic FC in the GM, the diagnosis accuracy for MCI subjects can be significantly improved even using RS‐fMRI data alone. Hum Brain Mapp 38:5019–5034, 2017. © 2017 Wiley Periodicals, Inc.     

Disrupted functional connectivity in white matter resting-state networks in unilateral temporal lobe epilepsy

Brain Imaging and Behavior - Unilateral temporal lobe epilepsy (TLE) is the most common type of focal epilepsy characterized by foci in the unilateral temporal lobe grey matters of regions such as...     

Cognition and resting-state functional connectivity in schizophrenia

Individuals with schizophrenia consistently display deficits in a multitude of cognitive domains, but the neurobiological source of these cognitive impairments remains unclear. By analyzing the functional connectivity of resting-state functional magnetic resonance imaging (rs-fcMRI) data in clinical populations like schizophrenia, research groups have begun elucidating abnormalities in the intrinsic communication between specific brain regions, and assessing relationships between these abnormalities and cognitive performance in schizophrenia. Here we review studies that have reported analysis of these brain–behavior relationships. Through this systematic review we found that patients with schizophrenia display abnormalities within and between regions comprising (1) the cortico-cerebellar-striatal-thalamic loop and (2) task-positive and task-negative cortical networks. Importantly, we did not observe unique relationships between specific functional connectivity abnormalities and distinct cognitive domains, suggesting that the observed functional systems may underlie mechanisms that are shared across cognitive abilities, the disturbance of which could contribute to the “generalized” cognitive deficit found in schizophrenia. We also note several areas of methodological change that we believe will strengthen this literature.     

Increased neural connectivity between the hypothalamus and cortical resting-state functional networks in chronic migraine

Journal of Neurology - The findings of resting-state functional MRI studies have suggested that abnormal functional integration between interconnected cortical networks characterises the brain of...     

Altered resting-state functional connectivity and anatomical connectivity of hippocampus in schizophrenia

Hippocampus has been implicated in participating in the pathophysiology of schizophrenia. However, the functional and anatomical connectivities between hippocampus and other regions are rarely concurrently investigated in schizophrenia. In the present study, both functional magnetic resonance imaging (fMRI) during rest and diffusion tensor imaging (DTI) were performed on 17 patients with paranoid schizophrenia and 14 healthy subjects. Resting-state functional connectivities of the bilateral hippocampi were separately analyzed by selecting the anterior hippocampus as region of interest. The fornix body was reconstructed by diffusion tensor tractography, and the integrity of this tract was evaluated using fractional anisotropy (FA). In patients with schizophrenia, the bilateral hippocampi showed reduced functional connectivities to some regions which have been reported to be involved in episodic memory, such as posterior cingulate cortex, extrastriate cortex, medial prefrontal cortex, and parahippocampus gyrus. We speculated that these reduced connectivity may reflect the disconnectivity within a neural network related to the anterior hippocampus in schizophrenia. Meanwhile the mean FA of the fornix body was significantly reduced in patients, indicating the damage in the hippocampal anatomical connectivity in schizophrenia. The concurrence of the functional disconnectivity and damaged anatomical connectivity between the hippocampus and other regions in schizophrenia suggest that the functional–anatomical relationship need to be further investigated.     

Real‐time estimation of dynamic functional connectivity networks

Two novel and exciting avenues of neuroscientific research involve the study of task‐driven dynamic reconfigurations of functional connectivity networks and the study of functional connectivity in real‐time. While the former is a well‐established field within neuroscience and has received considerable attention in recent years, the latter remains in its infancy. To date, the vast majority of real‐time fMRI studies have focused on a single brain region at a time. This is due in part to the many challenges faced when estimating dynamic functional connectivity networks in real‐time. In this work, we propose a novel methodology with which to accurately track changes in time‐varying functional connectivity networks in real‐time. The proposed method is shown to perform competitively when compared to state‐of‐the‐art offline algorithms using both synthetic as well as real‐time fMRI data. The proposed method is applied to motor task data from the Human Connectome Project as well as to data obtained from a visuospatial attention task. We demonstrate that the algorithm is able to accurately estimate task‐related changes in network structure in real‐time. Hum Brain Mapp 38:202–220, 2017. © 2016 Wiley Periodicals, Inc.     

Aberrant connectivity of resting-state networks in borderline personality disorder

Background

Several functional neuroimaging studies have reported regionally abnormal activation of the frontal cortex in individuals with borderline personality disorder (BPD) during cognitive and affective task performance. However, little is known about neural function in individuals with BPD during the resting state. Using functional magnetic resonance imaging (fMRI), this study investigated the functional connectivity of prefrontal and limbic networks in patients with BPD.

Methods

Between January 2009 and March 2010, we investigated patients with BPD according to DSM-IV criteria and healthy controls by means of resting-state fMRI. The data were analyzed using a spatial group independent component analysis, and random effects t tests were used to compare spatial components between groups (p < 0.005, uncorrected).

Results

There were 17 women with BPD and 17 female healthy controls enrolled in this study. Within a network comprising cortical midline regions (“default mode network”), patients with BPD showed an increase in functional connectivity in the left frontopolar cortex (FPC) and the left insula, whereas decreased connectivity was found in the left cuneus. Within a network comprising predominantly right lateral prefrontal and bilateral parietal regions, patients with BPD showed decreased connectivity of the left inferior parietal lobule and the right middle temporal cortex compared with healthy controls. Two networks comprising lateral prefrontal and cingulate regions did not exhibit significant between-group differences. We found correlations between functional connectivity of the FPC and measures of impulsivity as well as between connectivity of the insula/cuneus and dissociation tension.

Limitations

Co-occurrent axis I disorders and medication use in this sample of patients with BPD have to be considered as potential limitations.

Conclusion

These data suggest that abnormal functional connectivity of temporally coherent resting-state networks may underlie certain symptom clusters in patients with BPD.     

Residual functional connectivity in the split-brain revealed with resting-state functional MRI

Split-brain patients present a unique opportunity to address controversies regarding subcortical contributions to interhemispheric coordination. We characterized residual functional connectivity in a complete commissurotomy patient by examining patterns of low-frequency BOLD functional MRI signal. Using independent components analysis and region-of-interest-based functional connectivity analyses, we demonstrate bilateral resting state networks in a patient lacking all major cerebral commissures. Compared with a control group, the patient's interhemispheric correlation scores fell within the normal range for two out of three regions examined. Thus, we provide evidence for bilateral resting state networks in a patient with complete commissurotomy. Such continued interhemispheric interaction suggests that, at least in part, cortical networks in the brain can be coordinated by subcortical mechanisms.     

Age-related changes in resting-state functional connectivity in older adults

Age-related changes in the brain connectivity of healthy older adults have been widely studied in recent years, with some differences in the obtained results. Most of these studies showed decreases in general functional connectivity, but they also found increases in some particular regions and areas. Frequently, these studies compared young individuals with older subjects, but few studies compared different age groups only in older populations. The purpose of this study is to analyze whole-brain functional connectivity in healthy older adult groups and its network characteristics through functional segregation. A total of 114 individuals, 48 to 89 years old, were scanned using resting-state functional magnetic resonance imaging in a resting state paradigm and were divided into six different age groups( 60, 60–64, 65–69, 70–74, 75–79,≥ 80 years old). A partial correlation analysis, a pooled correlation analysis and a study of 3-cycle regions with prominent connectivity were conducted. Our results showed progressive diminution in the functional connectivity among different age groups and this was particularly pronounced between 75 and 79 years old.The oldest group(≥ 80 years old) showed a slight increase in functional connectivity compared to the other groups. This occurred possibly because of compensatory mechanism in brain functioning. This study provides information on the brain functional characteristics of every age group, with more specific information on the functional progressive decline, and supplies methodological tools to study functional connectivity characteristics. Approval for the study was obtained from the ethics committee of the Comisión de Bioética de la Universidad de Barcelona(approval No. PSI2012-38257) on June 5, 2012, and from the ethics committee of the Barcelona's Hospital Clínic(approval No. 2009-5306 and 2011-6604) on October 22, 2009 and April 7, 2011 respectively.     

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.     

Altered resting-state functional connectivity of the cerebellum in schizophrenia

Structural and functional abnormalities of the cerebellum in schizophrenia have been reported. Most previous studies investigating resting-state functional connectivity (rsFC) have relied on a priori restrictions on seed regions or specific networks, which may bias observations. In this study, we aimed to elicit the connectivity alterations of the cerebellum in schizophrenia in a hypothesis-free approach. Ninety-five schizophrenia patients and 93 sex- and age-matched healthy controls underwent resting-state functional magnetic resonance imaging (fMRI). A voxel-wise data-driven method, resting-state functional connectivity density (rsFCD), was used to investigate cerebellar connectivity changes in schizophrenia patients. Regions with altered rsFCD were chosen as seeds to perform seed-based resting-state functional connectivity (rsFC) analyses. We found that schizophrenia patients exhibited decreased rsFCD in the right hemispheric VI; moreover, this cerebellar region showed increased rsFC with the prefrontal cortex and subcortical nuclei and decreased rsFC with the visual cortex and sensorimotor cortex. In addition, some rsFC changes were associated with positive symptoms. These findings suggest that abnormalities of the cerebellar hub and cerebellar-subcortical-cortical loop may be the underlying mechanisms of schizophrenia.     

Altered functional connectivity networks of hippocampal subregions in remitted late-onset depression:a longitudinal resting-state study

The regional specifi city of hippocampal abnormalities in late-life depression(LLD) has been demonstrated in previous studies. In this study,we sought to examine the functional connectivity(FC) patterns of hippocampal subregions in remitted late-onset depression(r LOD),a special subtype of LLD. Fourteen r LOD patients and 18 healthy controls underwent clinical and cognitive evaluations as well as resting-state functional magnetic resonance imaging scans at baseline and at ~21 months of follow-up. Each hippocampus was divided into three parts,the cornu ammonis(CA),the dentate gyrus,and the subicular complex,and then six seed-based hippocampal subregional networks were established.Longitudinal changes of the six networks over time were directly compared between the rL OD and control groups. From baseline to follow-up,the r LOD group showed a greater decline in connectivity of the left CA to the bilateral posterior cingulate cortex/precuneus(PCC/PCUN),but showed increased connectivity of the right hippocampal subregional networks with the frontal cortex(bilateral medial prefrontal cortex/anterior cingulate cortex and supplementary motor area). Further correlative analyses revealed thatthe longitudinal changes in FC between the left CA and PCC/PCUN were positively correlated with longitudinal changes in the Symbol Digit Modalities Test(r = 0.624,P = 0.017) and the Digit Span Test(r = 0.545,P = 0.044) scores in the r LOD group. These results may provide insights into the neurobiological mechanism underlying the cognitive dysfunction in r LOD patients.     

Amygdala-orbitofrontal resting-state functional connectivity is associated with trait anger

An important distinction in research on the neural mechanisms of emotion regulation involves the relatively limited duration of emotional states versus emotional traits that are defined as the stable tendency to experience particular emotions in daily life. Neuroimaging investigations of the regulation of anger states point to the involvement of reciprocal changes in the prefrontal cortex and amygdala activity, but the neural substrate of trait anger has received less attention. We used resting-state functional MRI to determine whether the variation in the strength of functional connectivity between the amygdala and the orbitofrontal cortex is associated with trait anger. Sixteen healthy men completed the Spielberger State-Trait Anger Expression Inventory. Correlational analysis for resting-state functional connectivity (RSFC) was carried out with the left and the right amygdala as separate seed regions. Anger measures were correlated to RSFC involving the right and the left amygdala on a voxel-by-voxel basis across all individuals. We found that Trait Anger was inversely associated with the strength of RSFC between the amygdala and the contralateral middle orbitofrontal cortex. The association was stronger for the right amygdala-left orbitofrontal connection. Anger Control, the tendency to try to control expressions of anger, showed the opposite pattern of being positively correlated with amygdala-orbitofrontal connectivity. The present study provides evidence that RSFC in a corticolimbic circuit might subserve stable differences in anger regulation. Our findings also suggest that RSFC may prove valuable as a trait marker for disorders characterized by emotional dysregulation such as depression, anxiety, and personality disorders.     

Investigation of resting-state EEG functional connectivity in frontotemporal lobar degeneration

OBJECTIVE: To investigate the presence of EEG abnormalities in frontotemporal lobar degeneration (FTLD) in comparison with Alzheimer's disease (AD) and non-demented individuals with subjective memory complaints (SMC), using an elaborated visual EEG rating scale; furthermore, to investigate whether assessment of resting-state functional connectivity of the EEG is superior to visual evaluation in distinguishing between FTLD, AD and non-demented controls. METHODS: EEGs of 15 patients with FTLD, 20 with AD and 23 individuals with SMC were visually compared using the Grand Total EEG (GTE) score. The synchronization likelihood (SL) as a measure of functional connectivity between different EEG channels was calculated for the 0.5-4Hz, 4-8Hz, 8-10Hz, 10-13Hz, 13-30Hz and 30-45Hz frequency bands. Patients had mild to moderate dementia. RESULTS: In AD, as expected, the GTE revealed significant differences from FTLD and SMC, indicating more EEG slowing and loss of reactivity. Patients with FTLD, however, could not be discriminated from individuals with SMC by the GTE score. Analysis of resting-state functional connectivity showed decreased SL in AD compared to both FTLD and SMC in the lower and higher alpha frequency band and decreased SL in AD compared to SMC in the beta frequency band, whereas no differences between FTLD and AD or SMC were found. CONCLUSIONS: In patients with mild to moderate FTLD both the visually rated EEG and EEG measures of resting-state functional connectivity are normal. SIGNIFICANCE: Although widespread neuronal degeneration takes place in frontotemporal lobar degeneration, this is not reflected in the EEG during the mild to moderate stages of the disease. An abnormal EEG in a mildly demented subject favours a diagnosis of AD.     

Altered resting-state functional connectivity of the dentate nucleus in Parkinson's disease

We used functional magnetic resonance imaging (fMRI) to measure functional connectivity of the dentate nucleus (DN) between patients with Parkinson's disease (PD) and normal controls who were studied in a resting state. Images were acquired in 18 PD patients and in age- and sex-matched normal controls. Connectivity of the bilateral DN was calculated and compared between patients and controls, connectivity of the bilateral DN within the cerebellum was compared between rigidity and bradykinesia-dominant patients (PD_AR) and tremor-dominant patients (PD_T), and correlation analysis was performed between the connectivity strength and behavioral measures within the cerebellum. Some regions in the cerebellum showed enhanced connectivity with the bilateral DN in PD patients, and decreased connectivity of the DN with the bilateral cerebellar posterior lobe was observed in PD_T as compared to PD_AR. A set of regions consistent with the default mode network showed disrupted connectivity with the DN. Decreased connectivity between the inferior parietal lobule and the DN was also observed in PD patients. Additional analyses did not show any significant correlations between functional connectivity within the cerebellum and Unified Parkinson's Disease Rating Scale-III scores. Our findings suggest that connectivity of the DN in the resting state is disrupted in PD, and there may be a compensatory cerebellar connectivity mechanism in the resting state in PD. Further study of the cerebellum may clarify the pathophysiology of PD.     

抑郁症静息态大脑双侧杏仁核的功能连接

目的：探讨静息态下抑郁症患者大脑半球双侧杏仁核的功能连接特点,了解杏仁核及其功能相关脑区在抑郁症病理机制中的作用。方法：11例首次发作的重性抑郁症患者与11例性别、年龄、受教育程度均与患者相匹配的正常人完成静息态功能性磁共振成像（fMRI）扫描。利用Pearson相关分析方法分析受试者大脑双侧的杏仁核功能连接强度,并利用双样本t检验做组间对比,设P〈0．05为差异具有显著性。结果：静息态下,两组双侧杏仁核均具有明显的功能连接（P〈0．05）,而抑郁症组较对照组的功能连接明显减低（P=0．025）。结论：静息态下抑郁症组双侧杏仁核功能连接存在异常,这可能与抑郁症患者杏仁核异常及杏仁核与其他情感调节相关脑区的协调异常有关。