Altered Brain Functional Connectivity Research Articles

Disrupted rich club organization and structural brain connectome in unmedicated bipolar disorder.

Bipolar disorder (BD) has been associated with altered brain structural and functional connectivity. However, little is known regarding alterations of the structural brain connectome in BD. The present study aimed to use diffusion-tensor imaging (DTI) and graph theory approaches to investigate the rich club organization and white matter structural connectome in BD. Forty-two patients with unmedicated BD depression and 59 age-, sex- and handedness-matched healthy control participants underwent DTI. The whole-brain structural connectome was constructed by a deterministic fiber tracking approach. Graph theory analysis was used to examine the group-specific global and nodal topological properties, and rich club organizations, and then nonparametric permutation tests were used for group comparisons of network parameters. Compared with healthy control participants, the patients with BD showed abnormal global properties, including increased characteristic path length, and decreased global efficiency and local efficiency. Locally, the patients with BD showed abnormal nodal parameters (nodal strength, nodal efficiency, and nodal betweenness) predominantly in the parietal, orbitofrontal, occipital, and cerebellar regions. Moreover, the patients with BD showed decreased rich club and feeder connectivity density. Our results may reflect the disrupted white matter topological organization in the whole-brain, and abnormal regional connectivity supporting cognitive and affective functioning in depressed BD, which, in part, be due to impaired rich club connectivity.

Altered Functional Brain Connectivity in Mild Cognitive Impairment during a Cognitively Complex Car Following Task.

Mild cognitive impairment (MCI) can affect multiple cognitive abilities, leading to difficulty in performing complex, cognitively demanding daily tasks, such as driving. This study combined driving simulation and functional magnetic resonance imaging (fMRI) to investigate brain function in individuals with MCI while they performed a car-following task. The behavioral driving performance of 24 patients with MCI and 20 healthy age-matched controls was compared during a simulated car-following task. Functional brain connectivity during driving was analyzed for a separate cohort of 15 patients with MCI and 15 controls. Individuals with MCI had minor difficulty with lane maintenance, exhibiting significantly increased variability in steering compared to controls. Patients with MCI also exhibited reduced connectivity between fronto-parietal regions, as well as between regions involved in cognitive control (medial frontal cortex) and regions important for visual processing (cuneus, angular gyrus, superior occipital cortex, inferior and superior parietal cortex). Greater difficulty in lane maintenance (i.e., increased steering variability and lane deviations) among individuals with MCI was further associated with increased connectivity between the posterior cingulate cortex (PCC) and inferior frontal gyrus, as well as increased intra-cerebellar connectivity. Thus, compared to cognitively healthy controls, patients with MCI showed reduced connectivity between regions involved in visual attention, visual processing, cognitive control, and performance monitoring. Greater difficulty with lane maintenance among patients with MCI may reflect failure to inhibit components of the default-mode network (PCC), leading to interference with task-relevant networks as well as alterations in cerebellum connectivity.

F156. LONGITUDINAL WORKING MEMORY FUNCTIONAL DYSCONNECTIVITY REFLECTS HETEROGENEITY IN INDIVIDUALS AT ULTRA HIGH RISK FOR PSYCHOSIS

BackgroundVariation in trajectories of Ultra high-risk (UHR) psychosis mental state posts challenge to schizophrenia prevention or onset delay intervention. Our previous work described the heterogeneity at this prodromal stage of schizophrenia in both brain structure changes and resting-state functional network differences. Functional dysconnectivity can be one of the altered brain substrates underlying clinical symptoms. Lower resting-state functional connectivity (FC) within the salience network (SN) in schizophrenia was detectable at the UHR stage. FC between the frontoparietal network (FPN) and the SN was disrupted when network integration fell apart in the UHR state.FPN and SN are important for working memory (WM), which is largely compromised in schizophrenia and lesser in UHR group. Our previous work showed that WM task-related activation in the FPN and SN differed between the UHR and controls. Importantly, such differences varied with WM demands. Evidence has demonstrated that compared to resting-state FC, task-based FC may better predict behavioral performance. However, the WM-related FC in UHR group and its longitudinal changes are still largely unknown.To cover the gap, we sought to examine the heterogeneity in the WM task-related FC changes in a group of UHR participants over time. We expected WM-related FC would link to individual differences in clinical trajectories.MethodsBased on the longitudinal changes of UHR state within 2 years, participants were divided into 3 groups: 42 controls, 34 UHR remitters (UHR-R) and 42 UHR non-remitters (UHR-NR). We acquired fMRI (TR/TE = 2000/30 ms, 3 x 3 x 4 mm3, 28 slices) when participants performed WM task at different WM demands, varying from information maintenance alone (low) to requiring both maintenance and manipulation (high). We used seed-based approach (gPPI) to compare task-related FC of the FPN and the SN among groups. Voxel-wise FC with six seeds (bilateral anterior insula, parietal, and dorsal lateral prefrontal cortex, identified based on task activation) was regressed on WM demands and groups, controlling for age, gender, education, ethnicity, handedness and task accuracy. Linear mixed modeling methods were used to test longitudinal FC changes and the association between FC and clinical syndromes.ResultsTask performance was worse at high WM demand as expected, but no significant difference was found between groups or over time. Compared to controls, higher FC between the FPN (superior parietal gyrus) and the SN (insula) at low demand was observed in the UHR-NR group at baseline. Within the SN, WM-demand related FC between right insula and thalamus varied among 3 groups: low FC at low demand and high FC at high demand in controls; high FC at low demand but low FC at high demand in the UHR-R group. In contrast, UHR-NR group had high thalamus-insula FC in both WM demands.Moreover, longitudinal FC increase only occurred within the SN at high WM demand in the UHR-R group, while other task-related baseline group differences of FC remained stable over time. Importantly, the rate of intra-SN increase of FC over time at higher WM demand was associated with decline of the positive psychosis syndromes in the UHR-R group.DiscussionIn support of the functional dysconnectivity hypothesis, our study indicated that UHR state was accompanied by altered brain FC during WM task performance. In contrast to lower SN FC at rest, UHR state showed SN hyper-connectivity in task with low WM demand, suggesting the importance of studying UHR both at resting and in task. Importantly, intra-SN FC increase at high WM demand was linked to positive psychosis syndrome reduction in remitters, while no FC changes if UHR state persisted. We argued that task FC could reflect the clinical heterogeneity of the UHR group.

Non-negative discriminative brain functional connectivity for identifying schizophrenia on resting-state fMRI

BackgroundSchizophrenia is a clinical syndrome, and its causes have not been well determined. The objective of this study was to investigate the alteration of brain functional connectivity between schizophrenia and healthy control, and present a practical solution for accurately identifying schizophrenia at single-subject level.Methods24 schizophrenia patients and 21 matched healthy subjects were recruited to undergo the resting-state functional magnetic resonance imaging (rs-fMRI) scanning. First, we constructed the brain network by calculating the Pearson correlation coefficient between each pair of the brain regions. Then, this study proposed a novel non-negative discriminant functional connectivity selection method, i.e. non-negative elastic-net based method (N2EN), to extract the alteration of brain functional connectivity between schizophrenia and healthy control. It ranks the significance of the connectivity with a uniform criterion by introducing the non-negative constraint. Finally, kernel discriminant analysis (KDA) is exploited to classify the subjects with the selected discriminant brain connectivity features.ResultsThe proposed method is applied into schizophrenia classification, and achieves the sensitivity, specificity and accuracy of 100, 90.48 and 95.56%, respectively. Our findings also indicate the alteration of functional network can be used as the biomarks for guiding the schizophrenia diagnosis. The regions of cuneus, superior frontal gyrus, medial, paracentral lobule, calcarine fissure, surrounding cortex, etc. are highly relevant to schizophrenia.ConclusionsThis study provides a method for accurately identifying schizophrenia, which outperforms several state-of-the-art methods, including conventional brain network classification, multi-threshold brain network based classification, frequent sub-graph based brain network classification and support vector machine. Our investigation suggested that the selected discriminant resting-state functional connectivities are meaningful features for classifying schizophrenia and healthy control.

Altered brain functional connectivity and behaviour in a mouse model of maternal alcohol binge-drinking

Prenatal and perinatal alcohol exposure caused by maternal alcohol intake during gestation and lactation periods can have long-lasting detrimental effects on the brain development and behaviour of offspring. Children diagnosed with Foetal Alcohol Spectrum Disorders (FASD) display a wide range of cognitive, emotional and motor deficits, together with characteristic morphological abnormalities. Maternal alcohol binge drinking is particularly harmful for foetal and early postnatal brain development, as it involves exposure to high levels of alcohol over short periods of time. However, little is known about the long-term effects of maternal alcohol binge drinking on brain function and behaviour. To address this issue, we used pregnant C57BL/6 female mice with time-limited access to a 20% v/v alcohol solution as a procedure to model alcohol binge drinking during gestation and lactational periods. Male offspring were behaviourally tested during adolescence (30 days) and adulthood (60 days), and baseline neural metabolic capacity of brain regions sensitive to alcohol effects were also evaluated in adult animals from both groups. Our results show that prenatal and postnatal alcohol exposure caused age-dependent changes in spontaneous locomotor activity, increased anxiety-like behaviour and attenuated alcohol-induced conditioned place preference in adults. Also, significant changes in neural metabolic capacity using cytochrome c oxidase (CCO) quantitative histochemistry were found in the hippocampal dentate gyrus, the mammillary bodies, the ventral tegmental area, the lateral habenula and the central lobules of the cerebellum in adult mice with prenatal and postnatal alcohol exposure. In addition, the analysis of interregional CCO activity correlations in alcohol-exposed adult mice showed disrupted functional brain connectivity involving the limbic, brainstem, and cerebellar regions. Finally, increased neurogenesis was found in the dentate gyrus of the hippocampus of alcohol-exposed offspring, suggesting neuroadaptive effects due to early alcohol exposure. Our results demonstrate that maternal binge-like alcohol drinking causes long-lasting effects on motor and emotional-related behaviours associated with impaired neuronal metabolic capacity and altered functional brain connectivity.

Altered Brain Functional Hubs and Connectivity in Type 2 Diabetes Mellitus Patients: A Resting-State fMRI Study.

Type 2 diabetes mellitus (T2DM) affects a vast population and is closely associated with cognitive impairment. However, the mechanisms of cognitive impairment in T2DM patients have not been unraveled. Research on the basic units (nodes or hubs and edges) of the brain functional network on the basis of neuroimaging may advance our understanding of the network change pattern in T2DM patients. This study investigated the change patterns of brain functional hubs using degree centrality (DC) analysis and the connectivity among these hubs using functional connectivity and Granger causality analysis. Compared to healthy controls, the DC values were higher in the left anterior cingulate gyrus (ACG) and lower in the bilateral lateral occipital cortices (LOC) and right precentral gyrus (PreCG) in T2DM patients. The functional connectivity between the left ACG and the right PreCG was stronger in T2DM patients, whereas the functional connectivity among the right PreCG and bilateral LOC was weaker. A negative causal effect from the left ACG to left LOC and a positive effect from the left ACG to right LOC were observed in T2DM patients, while in healthy controls, the opposite occurred. Additionally, the reserve of normal brain function in T2DM patients was negatively associated with the elevated glycemic parameters. This study demonstrates that there are brain functional hubs and connectivity alterations that may reflect the aberrant information communication in the brain of T2DM patients. The findings may advance our understanding of the mechanisms of T2DM-related cognitive impairment.

Reduced orbitofrontal-thalamic functional connectivity related to suicidal ideation in patients with major depressive disorder

Despite recent developments in neuroimaging, alterations of brain functional connectivity in major depressive disorder (MDD) patients with suicidal ideation are poorly understood. This study investigated specific changes of suicidal ideation in functional connectivity of MDD patients. Whole brain functional connectivity in 46 patients with MDD (23 with suicidal ideation and 23 without) and 36 age- and gender- matched healthy controls were compared using resting-state functional Magnetic Resonance Imaging (fMRI) analyzed with network-based statistics (NBS) and graph-theoretical methods. Decreased functional connectivity in a characterized sub-network was observed in patients with MDD and suicidal ideation (FDR-adjusted p < 0.05). The sub-network included the regions of the fronto-thalamic circuits in the left hemisphere. The network measures of the left superior frontal gyrus, pars orbitalis (r = −0.40, p = 0.009), left thalamus (r = −0.41, p = 0.009), and right thalamus (r = −0.51, p = −0.002) were shown, through graph theoretical analysis, to be significantly negatively correlated with severity of suicidal ideation. The reduced functional connectivity in left orbitofrontal-both thalamic regions with suicidal ideation in MDD were inversely proportional to the severity of suicidality independent from depression severity. These findings suggest problems with decision-making and information integration in MDD patients with suicidal ideation.

Altered brain functional connectivity induced by physical exercise may improve neuropsychological functions in patients with benign epilepsy

ObjectiveThe objective of this study was to elucidate alteration in functional connectivity (FC) in patients with benign epilepsy with centrotemporal spikes (BECTS) as induced by physical exercise therapy and their correlation to the neuropsychological (NP) functions. MethodsWe analyzed 115 artifact- and spike-free 2-second epochs extracted from resting state EEG recordings before and after 5weeks of physical exercise in eight patients with BECTS. The exact Low Resolution Electromagnetic Tomography (eLORETA) was used for source reconstruction. We evaluated the cortical current source density (CSD) power across five different frequency bands (delta, theta, alpha, beta, and gamma). Altered FC between 34 regions of interests (ROIs) was then examined using lagged phase synchronization (LPS) method. We further investigated the correlation between the altered FC measures and the changes in NP test scores. ResultsWe observed changes in CSD power following the exercise for all frequency bands and statistically significant increases in the right temporal region for the alpha band. There were a number of altered FC between the cortical ROIs in all frequency bands of interest. Furthermore, significant correlations were observed between FC measures and NP test scores at theta and alpha bands. ConclusionThe increased localization power at alpha band may be an indication of the positive impact of exercise in patients with BECTS. Frequency band-specific alterations in FC among cortical regions were associated with the modulation of cognitive and NP functions. The significant correlation between FC and NP tests suggests that physical exercise may mitigate the severity of BECTS, thereby enhancing NP function.

Brain functional connectivity alterations in a rat model of excessive alcohol drinking: A resting-state network analysis.

Alcohol use disorders (AUD) are a major public health concern. Understanding the brain network alterations is of the utmost importance to diagnose and develop treatment strategies. Employing resting-state functional magnetic resonance imaging, we have performed a longitudinal study in a rat model of chronic excessive alcohol consumption, to identify functional alterations in brain networks triggered by alcohol drinking. Two time points were considered: 1) before alcohol consumption (control condition) and 2) after 30 days of alcohol drinking (alcohol condition). We first identified nine resting-state networks with group independent component analysis. Afterwards, dual regression was applied to obtain subject-specific time courses and spatial maps. L2-regularized partial correlation analysis between pairs of networks showed that functional connectivity (FC) between the retrosplenial-visual and striatal networks decreases due to alcohol consumption, whereas FC between the prefrontal-cingulate and striatal networks increases. Analysis of subject-specific spatial maps revealed FC decreases within networks after alcohol drinking, including the striatal, motor-parietal, prefrontal-cingulate, retrosplenial-visual and left motor-parietal networks. Overall, our results unveil a generalized decrease in brain FC induced by alcohol drinking in genetically predisposed animals, even after a relatively short period of exposure (1 month). The only exception to this hypo-connectivity state is the functional association between the striatal and prefrontal-cingulate networks, which increases after drinking, supporting evidence in human alcoholics.

Verbal working memory-related functional connectivity alterations in boys with attention-deficit/hyperactivity disorder and the effects of methylphenidate.

Few studies have investigated verbal working memory-related functional connectivity patterns in participants with attention-deficit/hyperactivity disorder (ADHD). Thus, we aimed to compare working memory-related functional connectivity patterns in healthy children and those with ADHD, and study effects of methylphenidate (MPH). Twenty-two boys with ADHD were scanned twice, under either MPH (single dose, 10 mg) or placebo, in a randomised, cross-over, counterbalanced placebo-controlled design. Thirty healthy boys were scanned once. We used fMRI during a numerical n-back task to examine functional connectivity patterns in case-control and MPH-placebo comparisons, using independent component analysis. There was no significant difference in behavioural performance between children with ADHD, treated with MPH or placebo, and healthy controls. Compared with controls, participants with ADHD under placebo showed increased functional connectivity within fronto-parietal and auditory networks, and decreased functional connectivity within the executive control network. MPH normalized the altered functional connectivity pattern and significantly enhanced functional connectivity within the executive control network, though in non-overlapping areas. Our study contributes to the identification of the neural substrates of working memory. Single dose of MPH normalized the altered brain functional connectivity network, but had no enhancing effect on (non-impaired) behavioural performance.

Multiple Neural Networks Malfunction in Primary Blepharospasm: An Independent Components Analysis.

Primary blepharospasm (BPS) is a focal dystonia characterized by involuntary blinking and eyelid spasms. The pathophysiology of BPS remains unclear. Several neuroimaging studies have suggested dysfunction of sensory processing and sensorimotor integration, but the results have been inconsistent. This study aimed to determine whether patients with BPS exhibit altered functional brain connectivity and to explore possible correlations between these networks and clinical variables. Twenty-five patients with BPS and 25 healthy controls were enrolled. We found that the patient group exhibited decreased connectivity within the sensory-motor network (SMN), which involved regions of the bilateral primary sensorimotor cortex, supplementary motor area (SMA), right premotor cortex, bilateral precuneus and left superior parietal cortex. Within the right fronto-parietal network, decreased connections were observed in the middle frontal gyrus, dorsal lateral prefrontal cortex and inferior frontal gyrus. Regarding the salience network (SN), increased connectivity was observed in the left superior frontal gyrus and middle frontal gyrus. These findings suggest the involvement of multiple neural networks in primary BPS.

Altered interhemispheric functional connectivity in patients with anisometropic and strabismic amblyopia: a resting-state fMRI study.

Altered brain functional connectivity has been reported in patients with amblyopia by recent neuroimaging studies. However, relatively little is known about the alterations in interhemispheric functional connectivity in amblyopia. The present study aimed to investigate the functional connectivity patterns between homotopic regions across hemispheres in patients with anisometropic and strabismic amblyopia under resting state. Nineteen monocular anisometropic amblyopia (AA), 18 strabismic amblyopia (SA), and 20 normal-sight controls (NC) were enrolled in this study. After a comprehensive ophthalmologic examination, resting-state fMRI scanning was performed in all participants. The pattern of the interhemispheric functional connectivity was measured with the voxel-mirrored homotopic connectivity (VMHC) approach. VMHC values differences within and between three groups were compared, and correlations between VMHC values and each the clinical variable were also analyzed. Altered VMHC was observed in AA and SA patients in lingual gyrus and fusiform gyrus compared with NC subjects. The altered VMHC of lingual gyrus showed a pattern of AA > SA > NC, while the altered VMHC of fusiform gyrus showed a pattern of AA > NC > SA. Moreover, the VMHC values of lingual gyrus were positively correlated with the stereoacuity both in AA and SA patients, and the VMHC values of fusiform gyrus were positively correlated with the amount of anisometropia just in AA patients. These findings suggest that interhemispheric functional coordination between several homotopic visual-related brain regions is impaired both in AA and SA patients under resting state and revealed the similarities and differences in interhemispheric functional connectivity between the anisometropic and strabismic amblyopia.

Altered Brain Functional Connectivity in Small-Cell Lung Cancer Patients after Chemotherapy Treatment: A Resting-State fMRI Study.

Previous studies in small-cell lung cancer (SCLC) patients have mainly focused on exploring neurocognitive deficits associated with prophylactic cranial irradiation (PCI). Little is known about functional brain alterations that might occur due to chemotherapy treatment in this population before PCI is administered. For this reason, we used resting-state functional Magnetic Resonance Imaging (fMRI) to examine potential functional connectivity disruptions in brain networks, including the Default Mode Network (DMN), the Sensorimotor Network, and the Task-Positive Network (TPN). Nineteen SCLC patients after platinum-based chemotherapy treatment and thirteen controls were recruited in the current study. ROI-to-ROI and Seed-to-Voxel analyses were carried out and revealed functional connectivity deficits in patients within all the networks investigated demonstrating the possible negative effect of chemotherapy in cognitive functions in SCLC populations.

Altered functional brain connectivity in patients with visually induced dizziness.

BackgroundVestibular patients occasionally report aggravation or triggering of their symptoms by visual stimuli, which is called visually induced dizziness (VID). These patients therefore experience dizziness, discomfort, disorientation and postural unsteadiness. The underlying pathophysiology of VID is still poorly understood.ObjectiveThe aim of the current explorative study was to gain a first insight in the underlying neural aspects of VID.MethodsWe included 10 VID patients and 10 healthy matched controls, all of which underwent a resting state fMRI scan session. Changes in functional connectivity were explored by means of the intrinsic connectivity contrast (ICC). Seed-based analysis was subsequently performed in visual and vestibular seeds.ResultsWe found a decreased functional connectivity in the right central operculum (superior temporal gyrus), as well as increased functional connectivity in the occipital pole in VID patients as compared to controls in a hypothesis-free analysis. A weaker functional connectivity between the thalamus and most of the right putamen was measured in VID patients in comparison to controls in a seed-based analysis. Furthermore, also by means of a seed-based analysis, a decreased functional connectivity between the visual associative area and the left parahippocampal gyrus was found in VID patients. Additionally, we found increased functional connectivity between thalamus and occipital and cerebellar areas in the VID patients, as well as between the associative visual cortex and both middle frontal gyrus and precuneus.ConclusionsWe found alterations in the visual and vestibular cortical network in VID patients that could underlie the typical VID symptoms such as a worsening of their vestibular symptoms when being exposed to challenging visual stimuli. These preliminary findings provide the first insights into the underlying functional brain connectivity in VID patients. Future studies should extend these findings by employing larger sample sizes, by investigating specific task-based paradigms in these patients and by exploring the implications for treatment.

Functional connectivity disruptions correlate with cognitive phenotypes in Parkinson's disease.

Cognitive deficits in Parkinson's disease are thought to be related to altered functional brain connectivity. To date, cognitive-related changes in Parkinson's disease have never been explored with dense-EEG with the aim of establishing a relationship between the degree of cognitive impairment, on the one hand, and alterations in the functional connectivity of brain networks, on the other hand.This study was aimed at identifying altered brain networks associated with cognitive phenotypes in Parkinson's disease using dense-EEG data recorded during rest with eyes closed. Three groups of Parkinson's disease patients (N = 124) with different cognitive phenotypes coming from a data-driven cluster analysis, were studied: G1) cognitively intact patients (63), G2) patients with mild cognitive deficits (46) and G3) patients with severe cognitive deficits (15). Functional brain networks were identified using a dense-EEG source connectivity method. Pairwise functional connectivity was computed for 68 brain regions in different EEG frequency bands. Network statistics were assessed at both global (network topology) and local (inter-regional connections) level.Results revealed progressive disruptions in functional connectivity between the three patient groups, typically in the alpha band. Differences between G1 and G2 (p < 0.001, corrected using permutation test) were mainly frontotemporal alterations. A statistically significant correlation (ρ = 0.49, p < 0.001) was also obtained between a proposed network-based index and the patients' cognitive score. Global properties of network topology in patients were relatively intact.These findings indicate that functional connectivity decreases with the worsening of cognitive performance and loss of frontotemporal connectivity may be a promising neuromarker of cognitive impairment in Parkinson's disease.

Altered functional brain connectivity in children and young people with opsoclonus-myoclonus syndrome.

Opsoclonus-myoclonus syndrome (OMS) is a rare, poorly understood condition that can result in long-term cognitive, behavioural, and motor sequelae. Several studies have investigated structural brain changes associated with this condition, but little is known about changes in function. This study aimed to investigate changes in brain functional connectivity in patients with OMS. Seven patients with OMS and 10 age-matched comparison participants underwent 3T magnetic resonance imaging (MRI) to acquire resting-state functional MRI data (whole-brain echo-planar images; 2mm isotropic voxels; multiband factor ×2) for a cross-sectional study. A seed-based analysis identified brain regions in which signal changes over time correlated with the cerebellum. Model-free analysis was used to determine brain networks showing altered connectivity. In patients with OMS, the motor cortex showed significantly reduced connectivity, and the occipito-parietal region significantly increased connectivity with the cerebellum relative to the comparison group. A model-free analysis also showed extensive connectivity within a visual network, including the cerebellum and basal ganglia, not present in the comparison group. No other networks showed any differences between groups. Patients with OMS showed reduced connectivity between the cerebellum and motor cortex, but increased connectivity with occipito-parietal regions. This pattern of change supports widespread brain involvement in OMS.

Resting-state functional MR imaging shed insights into the brain of diabetes.

Diabetes mellitus is a common metabolic disease which is associated with increasing risk for multiple cognitive declines. Alterations in brain functional connectivity are believed to be the mechanisms underlying the cognitive function impairments. During the past decade, resting-state functional magnetic resonance imaging (rs-fMRI) has been developed as a major tool to study brain functional connectivity in vivo. This paper briefly reviews the diabetes-associated cognitive impairment, analysis algorithms and clinical applications of rs-fMRI. We also provide future perspectives of rs-fMRI in diabetes.

Frequency-specific alterations in functional connectivity in treatment-resistant and -sensitive major depressive disorder

Major depressive disorder (MDD) may involve alterations in brain functional connectivity in multiple neural circuits and present large-scale network dysfunction. Patients with treatment-resistant depression (TRD) and treatment-sensitive depression (TSD) show different responses to antidepressants and aberrant brain functions. This study aims to investigate functional connectivity patterns of TRD and TSD at the whole brain resting state. Seventeen patients with TRD, 17 patients with TSD, and 17 healthy controls matched with age, gender, and years of education were recruited in this study. The brain was divided using an automated anatomical labeling atlas into 90 regions of interest, which were used to construct the entire brain functional networks. An analysis method called network-based statistic was used to explore the dysconnected subnetworks of TRD and TSD at different frequency bands. At resting state, TSD and TRD present characteristic patterns of network dysfunction at special frequency bands. The dysconnected subnetwork of TSD mainly lies in the fronto-parietal top-down control network. Moreover, the abnormal neural circuits of TRD are extensive and complex. These circuits not only depend on the abnormal affective network but also involve other networks, including salience network, auditory network, visual network, and language processing cortex. Our findings reflect that the pathological mechanism of TSD may refer to impairment in cognitive control, whereas TRD mainly triggers the dysfunction of emotion processing and affective cognition. This study reveals that differences in brain functional connectivity at resting state reflect distinct pathophysiological mechanisms in TSD and TRD. These findings may be helpful in differentiating two types of MDD and predicting treatment responses.

Long-range dysconnectivity in frontal and midline structures is associated to psychosis in 22q11.2 deletion syndrome.

Patients affected by 22q11.2 deletion syndrome (22q11DS) present a characteristic cognitive and psychiatric profile and have a genetic predisposition to develop schizophrenia. Although brain morphological alterations have been shown in the syndrome, they do not entirely account for the complex clinical picture of the patients with 22q11DS and for their high risk of psychotic symptoms. Since Friston proposed the "disconnection hypothesis" in 1998, schizophrenia is commonly considered as a disorder of brain connectivity. In this study, we review existing evidence pointing to altered brain structural and functional connectivity in 22q11DS, with a specific focus on the role of dysconnectivity in the emergence of psychotic symptoms. We show that widespread alterations of structural and functional connectivity have been described in association with 22q11DS. Moreover, alterations involving long-range association tracts as well as midline structures, such as the corpus callosum and the cingulate gyrus, have been associated with psychotic symptoms in this population. These results suggest common mechanisms for schizophrenia in syndromic and non-syndromic populations. Future directions for investigations are also discussed.

Abnormal degree centrality in Alzheimer's disease patients with depression: A resting-state functional magnetic resonance imaging study

Depression is common in Alzheimer's disease (AD) and occurs in AD patients with a prevalence of up to 40%. It reduces cognitive function and increases the burden on caregivers. Currently, there are very few medications that are useful for treating depression in AD patients. Therefore, understanding the brain abnormalities in AD patients with depression (D-AD) is crucial for developing effective interventions. The aim of this study was to investigate the intrinsic dysconnectivity pattern of whole-brain functional networks at the voxel level in D-AD patients based on degree centrality (DC) as measured by resting-state functional magnetic resonance imaging (R-fMRI). Our study included 32 AD patients. All patients were evaluated using the Neuropsychiatric Inventory and Hamilton Depression Rating Scale and further divided into two groups: 15 D-AD patients and 17 non-depressed AD (nD-AD) patients. R-fMRI datasets were acquired from these D-AD and nD-AD patients. First, we performed a DC analysis to identify voxels that showed altered whole brain functional connectivity (FC) with other voxels. We then further investigated FC using the abnormal DC regions to examine in more detail the connectivity patterns of the identified DC changes. D-AD patients had lower DC values in the right middle frontal, precentral, and postcentral gyrus than nD-AD patients. Seed-based analysis revealed decreased connectivity between the precentral and postcentral gyrus to the supplementary motor area and middle cingulum. FC also decreased in the right middle frontal, precentral, and postcentral gyrus. Thus, AD patients with depression fit a ‘network dysfunction model’ distinct from major depressive disorder and AD.