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.     

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.     

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 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.     

Altered resting-state amygdala functional connectivity in men with posttraumatic stress disorder

Background

Converging neuroimaging research suggests altered emotion neurocircuitry in individuals with posttraumatic stress disorder (PTSD). Emotion activation studies in these individuals have shown hyperactivation in emotion-related regions, including the amygdala and insula, and hypoactivation in emotion-regulation regions, including the medial prefrontal cortex (mPFC) and anterior cingulate cortex (ACC). However, few studies have examined patterns of connectivity at rest in individuals with PTSD, a potentially powerful method for illuminating brain network structure.

Methods

Using the amygdala as a seed region, we measured resting-state brain connectivity using 3 T functional magnetic resonance imaging in returning male veterans with PTSD and combat controls without PTSD.

Results

Fifteen veterans with PTSD and 14 combat controls enrolled in our study. Compared with controls, veterans with PTSD showed greater positive connectivity between the amygdala and insula, reduced positive connectivity between the amygdala and hippocampus, and reduced anticorrelation between the amygdala and dorsal ACC and rostral ACC.

Limitations

Only male veterans with combat exposure were tested, thus our findings cannot be generalized to women or to individuals with non–combat related PTSD.

Conclusion

These results demonstrate that studies of functional connectivity during resting state can discern aberrant patterns of coupling within emotion circuits and suggest a possible brain basis for emotion-processing and emotion-regulation deficits in individuals with PTSD.     

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.     

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.     

Altered resting-state voxel-level whole-brain functional connectivity in multiple system atrophy patients with cognitive impairment

ObjectiveThere is increasing evidence of cognitive impairment (CI) frequently occurring in patients with multiple system atrophy (MSA); however, the neurobiological mechanisms underlying CI in patients with MSA remain unclear.MethodsWe enrolled 61 patients with probable MSA and 33 healthy controls (HC). We used degree centrality (DC) analysis to assess changes in the centrality level of MSA-CI related brain nodes. We conducted a secondary seed-based functional connectivity (FC) analysis to investigate dysfunctions in cognitive networks related to MSA. Further, we analysed the correlation between clinical symptoms and acquired connectivity measures.ResultsCompared with HC, patients with MSA-CI and those with MSA with normal cognition (MSA-NCI) exhibited lower DC values in the left calcarine and right postcentral regions and higher DC values in the bilateral caudate and left precuneus. There were significant differences in the DC values in the right middle prefrontal gyrus between the MSA-CI and MSA-NCI groups. The mean DC values in the right middle prefrontal gyrus (RMPFG) were correlated with clinical cognitive severity. Consequently, we used this brain region as a seed in secondary seed-based FC analysis and observed FC changes within the right precuneus, inferior parietal lobe, and right insula.ConclusionsDecreased middle prefrontal cortex activity and its altered functional connectivity with the precuneus, inferior parietal lobe, and insula are possible biomarkers of cognitive dysfunction in patients with MSA-CI.SignificanceCognitive impairment in MSA is associated with alterations in the dorsolateral prefrontal cortex network.     

Altered functional connectivity in default mode network in absence epilepsy: a resting-state fMRI study

Dysfunctional default mode network (DMN) has been observed in various mental disorders, including epilepsy (see review Broyd et al. [2009]: Neurosci Biobehav Rev 33:279–296). Because interictal epileptic discharges may affect DMN, resting-state fMRI was used in this study to determine DMN functional connectivity in 14 healthy controls and 12 absence epilepsy patients. To avoid interictal epileptic discharge effects, testing was performed within interictal durations when there were no interictal epileptic discharges. Cross-correlation functional connectivity analysis with seed at posterior cingulate cortex, as well as region-wise calculation in DMN, revealed decreased integration within DMN in the absence epilepsy patients. Region-wise functional connectivity among the frontal, parietal, and temporal lobe was significantly decreased in the patient group. Moreover, functional connectivity between the frontal and parietal lobe revealed a significant negative correlation with epilepsy duration. These findings indicated DMN abnormalities in patients with absence epilepsy, even during resting interictal durations without interictal epileptic discharges. Abnormal functional connectivity in absence epilepsy may reflect abnormal anatomo-functional architectural integration in DMN, as a result of cognitive mental impairment and unconsciousness during absence seizure.     

抑郁症静息态默认状态网络内功能连接的初步探讨

目的 通过分析静息态下抑郁症患者默认状态网络内脑区间功能连接效能,探讨默认状态网络在抑郁症病理机制中的作用.方法 15例符合中国精神障碍分类及诊断标准第3版(CCMD-3)抑郁发作和美国精神障碍诊断与统计手册第4版(DSM-Ⅳ)重性抑郁症诊断标准的首发抑郁症患者与14名正常对照完成功能磁共振成像扫描.分析受试者默认状态网络内脑区的功能连接强度并比较其组问差异.结果 与正常对照比较,抑郁症患者双侧前额中部与楔前叶、双侧后扣带回与前额中部、右后扣带回与楔前叶、双侧前扣带回腹侧与前额中部的功能连接减低(P＜0.05).结论 静息态下抑郁症患者默认状态网络内脑区间的连接效能存在异常,这可能在抑郁症的病理机制中发挥了重要作用.     

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.     

Altered executive control network resting-state connectivity in social anxiety disorder

Objectives: Research into the neural basis of social anxiety disorder (SAD) suggests alterations in prefrontal networks, which may in turn disrupt regulation of the limbic system. Better understanding of the disturbed interface between these networks may improve current pathogenic models of this disorder. Methods: Applying group independent component analysis (ICA) to recordings of fMRI resting-state, connectivity in the executive control network was studied in 18 patients with SAD and 15 age- and sex-matched healthy controls. Results: Results revealed a dissociation within the left executive control network, with SAD patients showing decreased connectivity of the orbitofrontal gyrus and increased connectivity of the middle frontal gyrus compared to healthy controls. In a subsequent seed-based functional connectivity analysis, patients with SAD displayed increased connectivity between the left orbitofrontal gyrus and the left amygdala. Conclusions: Findings suggest that hypo-connectivity in the executive control network and hyper-connectivity between the orbitofrontal cortex and the amygdala may reflect a disturbance in the balance between top-down and bottom-up control processes, potentially contributing to the development of SAD.     

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 resting-state thalamo-occipital functional connectivity is associated with cognition in isolated rapid eye movement sleep behavior disorder

ObjectiveIsolated rapid eye movement sleep behavior disorder (iRBD) patients are at risk of cognitive impairments, however the underlying mechanism is still unclear. This study aimed to evaluate thalamo-cortical functional connectivity (FC) using resting-state functional magnetic resonance imaging (fMRI) and its correlation with cognitive dysfunction in patients with iRBD.MethodsA total 37 polysomnographies (PSGs) confirmed iRBD patients and 15 age-sex matched controls underwent resting-state fMRI and comprehensive neuropsychological assessment. Thalamo-cortical FC was evaluated by using seed-to voxel analysis and was compared between the iRBD and controls. Correlation between the average value of significant clusters and cognitive function scores in iRBD were calculated.ResultsCompared to the control subjects, patients with iRBD patients showed cognitive decline in word list recognition (p = 0.016), and constructional recall (p = 0.044). The FC analysis showed increased FC between the left thalamus and occipital regions including the right cuneal cortex, left fusiform gyrus and lingual gyrus (cluster level p < 0.05, corrected for false discovery rate). The averaged thalamo-fusiform FC value positively correlated with word list recognition after adjusting for age and sex (adjusted r = 0.347, p = 0.041).ConclusionThalamic resting state FC is altered in iRBD patients and is associated with the cognitive function. Enhancement of the thalamo-occipital FC may reflect a compensatory mechanism for cognitive impairment in iRBD.     

Altered resting-state network connectivity in panic disorder: an independent ComponentAnalysis

Panic disorder (PD) is a prevalent anxiety disorder but its neurobiology remains poorly understood. It has been proposed that the pathophysiology of PD is related to an abnormality in a particular neural network. However, most studies investigating resting-state functional connectivity (FC) have relied on a priori restrictions of seed regions, which may bias observations. This study investigated changes in intra and internetwork FC in the whole brain of patients with PD using resting-state functional magnetic resonance imaging. A voxel-wise data-driven independent component analysis was performed on 26 PD patients and 27 healthy controls (HCs).We compared the differences in the intra and internetwork FC between the two groups of subjects using statistical parametric mapping with two-sample t-tests. PD patients exhibited decreased intra-network FC in the right anterior cingulate cortex (ACC) of the anterior default mode network, the left precentral and postcentral gyrus of the sensorimotor network, the right lobule V/VI, the cerebellum vermis, and the left lobule VI of the cerebellum network compared with the HCs. The intra-network FC in the right ACC was negatively correlated with symptom severity. None of the pairs of resting state networks showed significant differences in functional network connectivity between the two groups. These results suggest that the brain networks associated with emotion regulation, interoceptive awareness, and fear and somatosensory processing may play an important role in the pathophysiology of PD.

     

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.