Remote Functional Connectivity Research Articles

Altered local and remote functional connectivity in mild Alzheimer's disease patients with sleep disturbances.

This study aimed to investigate local and remote functional connectivity in mild Alzheimer's disease patients with sleep disturbances (ADSD) and those without sleep disturbances (ADNSD). Thirty eight mild AD patients with sleep disturbances and 21 mild AD patients without sleep disturbances participated in this study. All subjects underwent neuropsychological assessments and 3.0 Tesla magnetic resonance scanning. Static and dynamic regional homogeneity (ReHo) were used to represent the local functional connectivity. Seed-based whole-brain functional connectivity was used to represent the remote functional connectivity. The seed was chosen based on the results of ReHo. Compared to ADNSD, ADSD showed decreased static ReHo in the left posterior central gyrus and the right cuneus and increased dynamic ReHo in the left posterior central gyrus. As for the remote functional connectivity, comparing ADSD to ADNSD, it was found that there was a decreased functional connection between the left posterior central gyrus and the left cuneus as well as the left calcarine. The current study demonstrated that, compared with ADNSD, ADSD is impaired in both local and remote functional connectivity, manifested as reduced functional connectivity involving the primary sensory network and the primary visual network. The abnormality of the above functional connectivity is one of the reasons why sleep disorders promote cognitive impairment in AD. Moreover, sleep disorders change the temporal sequence of AD pathological damage to brain functional networks, but more evidence is needed to support this conclusion.

Stratifying ASD and characterizing the functional connectivity of subtypes in resting-state fMRI

Although stratifying autism spectrum disorder (ASD) into different subtypes is a common effort in the research field, few papers have characterized the functional connectivity alterations of ASD subgroups classified by their clinical presentations. This is a case-control rs-fMRI study, based on large samples of open database (Autism Brain Imaging Data Exchange, ABIDE). The rs-MRI data from n=415 ASD patients (males n=357), and n=574 typical development (TD) controls (males n=410) were included. Clinical features of ASD were extracted and classified using data from each patient's Autism Diagnostic Interview-Revised (ADI-R) evaluation. Each subtype of ASD was characterized by local functional connectivity using regional homogeneity (ReHo) for assessment, remote functional connectivity using voxel-mirrored homotopic connectivity (VMHC) for assessment, the whole-brain functional connectivity, and graph theoretical features. These identified imaging properties from each subtype were integrated to create a machine learning model for classifying ASD patients into the subtypes based on their rs-fMRI data, and an independent dataset was used to validate the model. All ASD participants were classified into Cluster-1 (patients with more severe impairment) and Cluster-2 (patients with moderate impairment) according to the dimensional scores of ADI-R. When compared to the TD group, Cluster-1 demonstrated increased local connection and decreased remote connectivity, and widespread hyper- and hypo-connectivity variations in the whole-brain functional connectivity. Cluster-2 was quite similar to the TD group in both local and remote connectivity. But at the level of whole-brain functional connectivity, the MCC-related connections were specifically impaired in Cluster-2. These properties of functional connectivity were fused to build a machine learning model, which achieved ~75% for identifying ASD subtypes (Cluster-1 accuracy = 81.75%; Cluster-2 accuracy = 76.48%). The stratification of ASD by clinical presentations can help to minimize disease heterogeneity and highlight the distinguished properties of brain connectivity in ASD subtypes.

Impact of APOE ε4 Carrier Status on Associations Between Subthreshold, Positive Amyloid-β Deposition, Brain Function, and Cognitive Performance in Cognitively Normal Older Adults: A Prospective Study.

BackgroundA growing body of evidence suggests a deteriorating effect of subthreshold amyloid-beta (Aβ) accumulation on cognition before the onset of clinical symptoms of Alzheimer's disease (AD). Despite the association between the Aβ-dependent pathway and the APOE ε4 allele, the impact of this allele on the progression from the subthreshold Aβ deposits to cognitive function impairment is unclear. Furthermore, the comparative analysis of positive Aβ accumulation in the preclinical phase is lacking.ObjectiveThis study aimed to explore the differential effect of the APOE ε4 carrier status on the association between Aβ deposition, resting-state brain function, and cognitive performance in cognitively normal (CN) older adults, depending on the Aβ burden status.MethodsOne hundred and eighty-two older CN adults underwent resting-state functional magnetic resonance imaging, [18F] flutemetamol (FMM) positron emission tomography, a neuropsychological battery, and APOE genotyping. We evaluated the resting-state brain function by measuring the local and remote functional connectivity (FC) and measured the remote FC in the default-mode network (DMN), central-executive network (CEN), and salience network (SN). In addition, the subjects were dichotomized into those with subthreshold and positive Aβ deposits using a neocortical standardized uptake value ratio with the cut-off value of 0.62, which was calculated with respect to the pons.ResultsThe present result showed that APOE ε4 carrier status moderated the relationship between Aβ deposition, local and remote resting-state brain function, and cognitive performance in each CN subthreshold and positive Aβ group. We observed the following: (i) the APOE ε4 carrier status-Aβ deposition and APOE ε4 carrier status-local FC interaction for the executive and memory function; (ii) the APOE ε4 carrier status-regional Aβ accumulation interaction for the local FC; and (iv) the APOE ε4 carrier status-local FC interaction for the remote inter-network FC between the DMN and CEN, contributing higher cognitive performance in the APOE ε4 carrier with higher inter-network FC. Finally, these results were modulated according to Aβ positivity.ConclusionThis study is the first attempt to thoroughly examine the influence of the APOE ε4 carrier status from the subthreshold to positive Aβ accumulation during the preclinical phase.

Local-to-Remote Brain Functional Connectivity in Patients with Thyroid-Associated Ophthalmopathy and Assessment of Its Predictive Value Using Machine Learning.

PurposeTo explore the alterations in both local and remote brain connectivity in patients with thyroid-associated ophthalmopathy (TAO) and to investigate whether the alterations of local neural function could be used to distinguish patients with TAO from healthy controls (HCs) using support vector machine (SVM) classifier.Materials and MethodsIn total, 21 patients with TAO and 21 well-matched HCs were enrolled in our study and underwent resting-state functional magnetic resonance imaging (rs-fMRI) scanning. We employed regional homogeneity (ReHo) algorithm to evaluate local neural function and selected significantly altered brain regions as seed areas for subsequent study of the remote functional connectivity (FC). Moreover, we chose the observed alterations in the ReHo analysis as classification features to differentiate patients with TAO from HCs through SVM classification method.ResultsCompared with the HCs, TAO patients showed significantly lower ReHo values in the right middle occipital gyrus (MOG) and right angular (ANG). In contrast, TAO patients displayed higher ReHo values in the left hippocampus (Hipp). We further found TAO patients exhibited decreased FC between the left and right Hipp, right MOG and left cerebellum (CER), right ANG and left rectus, right superior temporal pole gyrus (PSTG) (voxel-level p < 0.01, Gaussian random field correction, cluster-level p < 0.05). The alterations in local neural function exhibited an accuracy of 78.57% and area under curve of 0.81 for distinguishing the patients from HCs.ConclusionWe mainly found the results that patients with TAO showed significantly dysfunctional local and remote brain functional connectivity in several brain regions associated with visual and cognitive functions. The ReHo variability has potential value in differentiating patients with TAO from HCs. These findings may provide novel insights into the neurological mechanisms underlying visual and cognitive disorders in patients with TAO.

The predictive value of local to remote functional connectivity changes in comitant exotropia patients.

Comitant exotropia (CE) is a common eye disease with abnormal eye movement, whereas altered synchronous neural activity in CE patients is poorly understood. The purpose of our study was to investigate local to remote functional connectivity of blood oxygen level-dependent (BOLD) signals changes in CE patients. Thirty-four patients and thirty-four healthy controls (HCs) underwent resting-state MRI scans. The ReHo and FC method was applied to investigate the local to remote functional connectivity changes in CE patients. Compared to the HC group, CE patients showed significant increased ReHo values in the left cerebellar_crus2 and left middle frontal gyrus. Meanwhile, CE patients showed significant decreased ReHo values in the right middle temporal gyrus, left postcentral gyrus and right angular. Moreover, CE patients showed an increased FC between the cerebellar network, sensorimotor network (SMN) and default-mode network (DMN). The support vector machine (SVM) classification was up to a total accuracy of 94.12%. The AUC of the classification model was 0.99 on the basis of ReHo map. Our result highlights that CE patients had abnormal local to remote functional connectivity in the cerebellar network, SMN, DMN, which might indicate the neural mechanism of eye movements and stereo vision dysfunction in CE patients. Moreover, the SVM algorithm reveals ReHo maps as a potential biomarker for predicting clinical outcomes in CE patients.

Abnormal functional network centrality in drug-naïve boys with attention-deficit/hyperactivity disorder.

Attention-deficit/hyperactivity disorder (ADHD) is the most commonly diagnosed neurodevelopmental disorder in childhood and is characterized by inattention, impulsivity, and hyperactivity. Observations of distributed functional abnormalities in ADHD suggest aberrant large-scale brain network connectivity. However, few studies have measured the voxel-wise network centrality of boys with ADHD, which captures the functional relationships of a given voxel within the entire connectivity matrix of the brain. Here, to examine the network patterns characterizing children with ADHD, we recruited 47 boys with ADHD and 21 matched control boys who underwent resting-state functional imaging scanning in a 3.0 T MRI unit. We measured voxel-wise network centrality, indexing local functional relationships across the entire brain connectome, termed degree centrality (DC). Then, we chose the brain regions with altered DC as seeds to examine the remote functional connectivity (FC) of brain regions. We found that boys with ADHD exhibited (1) decreased centrality in the left superior temporal gyrus (STG) and increased centrality in the left superior occipital lobe (SOL) and right inferior parietal lobe(IPL); (2) decreased FC between the STG and the putamen and thalamus, which belong to the cognitive cortico-striatal-thalamic-cortical (CSTC) loop, and increased FC between the STG and medial/superior frontal gyrus within the affective CSTC loop; and (3) decreased connectivity between the SOL and cuneus within the dorsal attention network. Our results demonstrated that patients with ADHD show a connectivity-based pathophysiological process in the cognitive and affective CSTC loops and attention network.

Altered hemodynamics contribute to local but not remote functional connectivity disruption due to glioma growth

Glioma growth can cause pervasive changes in the functional connectivity (FC) of brain networks, which has been associated with re-organization of brain functions and development of functional deficits in patients. Mechanisms underlying functional re-organization in brain networks are not understood and efforts to utilize functional imaging for surgical planning, or as a biomarker of functional outcomes are confounded by the heterogeneity in available human data. Here we apply multiple imaging modalities in a well-controlled murine model of glioma with extensive validation using human data to explore mechanisms of FC disruption due to glioma growth. We find gliomas cause both local and distal changes in FC. FC changes in networks proximal to the tumor occur secondary to hemodynamic alterations but surprisingly, remote FC changes are independent of hemodynamic mechanisms. Our data strongly implicate hemodynamic alterations as the main driver of local changes in measurements of FC in patients with glioma.

F72. Contralesional brain activity in acute ischemic stroke

The non-injured, contralateral hemisphere is increasingly acknowledged in recovery from acute ischemic stroke. We estimate the value of conventional EEG recordings for identification of contralateral hemisphere involvement in relation to functional recovery. We analyzed two-minute epochs from 21 electrode EEG registrations from 18 patients with acute hemispheric ischemic stroke and compared with 18 age-matched controls. Outcome was dichotomized as good (mRS 0–2) or poor (mRS 3–5 or death) at three months. Effects of the infarct on the ipsi- and contralateral hemispheres were analyzed by the delta/alpha ratio (DAR) and two measures of functional connectivity (magnitude squared coherence (MSC) and weighted phase lag index (WPLI)). DAR was higher in patients than in controls, both in the ipsilateral and in the contralateral hemisphere (median 4.5 ± 6.7 ipsilateral and 2.4 ± 2.0 contralateral vs. 0.5 ± 0.5 in the control group, P < 0.001), indicating robust EEG changes in both lesioned and non-lesioned hemisphere. MSC and WPLI in the alpha and beta frequency bands were lower in patients than in controls in both hemispheres, indicating clear disturbances of functional connectivity (P < 0.05). In the poor outcome group, contralateral MSC and WPLI were lower than in the good outcome group, although these differences did not reach statistical significance. Short conventional EEG measurements show robust changes of brain activity and functional connectivity in both ipsilateral and contralateral hemisphere of patients with acute ischemic stroke. Changes of remote functional connectivity tend to interact with functional recovery. Associations between contralateral functional connectivity measures and incidence of apathy and depression are currently analyzed and will be presented.

Contralesional Brain Activity in Acute Ischemic Stroke

Background: The noninjured, contralateral hemisphere is increasingly acknowledged in the process of recovery from acute ischemic stroke. We estimated the value of conventional electroencephalography (EEG) recordings for identifying contralateral hemisphere involvement in relation to functional recovery. Methods: We analyzed 2-min epochs from 21 electrode EEG registrations of 18 patients with acute hemispheric ischemic stroke and compared with 18 age-matched controls. Outcome was dichotomized as good (modified Rankin Scale [mRS] 0–2) or poor (mRS 3–5 or death) at 3 months. Effects of the infarct on the ipsi-and contralateral hemispheres were analyzed by the delta/alpha ratio (DAR) and 2 measures of functional connectivity (magnitude squared coherence [MSC] and weighted phase lag index [WPLI]). Results: DAR was higher in patients than in controls, both in the ipsilateral and in the contralateral hemisphere (median 4.5 ± 6.7 ipsilateral and 2.4 ± 2.0 contralateral vs. 0.5 ± 0.5 in the control group, p < 0.001), indicating robust EEG changes in both lesioned and non-lesioned hemisphere. MSC and WPLI in the alpha and beta frequency bands were lower in patients than in controls in both hemispheres, indicating clear disturbances of functional connectivity (p < 0.05). In the poor outcome group, contralateral MSC and WPLI were lower than in the good outcome group, although these differences did not reach statistical significance. Conclusions: Short conventional EEG measurements show robust changes of brain activity and functional connectivity in both ipsilateral and contralateral hemispheres of patients with acute ischemic stroke. Changes of remote functional connectivity tend to interact with functional recovery. Future studies should estimate predictive values for individual patients and interactions with plasticity enhancing treatments.

Disrupted intrinsic and remote functional connectivity in heterotopia-related epilepsy.

Several neuroimaging studies have examined neural interactions in patients with periventricular nodular heterotopia (PNH). However, features of the underlying functional network remain poorly understood. In this study, we examined alterations in the local (regional) and remote (interregional) cerebral networks in this disorder. Twenty-eight subjects all having suffered from PNH with epilepsy, as well as 28 age- and sex- matched healthy controls, were enrolled in this study. Amplitude of low-frequency fluctuation (ALFF) and seed-based functional connectivity (FC) were calculated to detect regional neural function and functional network integration, respectively. Compared with healthy controls, patients with PNH-related epilepsy showed decreased ALFF in the ventromedial prefrontal cortex (vmPFC) and precuneus areas. ALFF values in both areas were negative correlated with epilepsy duration (P<.05, Bonferroni-corrected). Furthermore, patients with PNH-related epilepsy had increased remote interregional FC mainly in bilateral prefrontal and parietal cortices, supramarginal gyrus, dorsal cingulate gyrus, and right insula; lower FC was found in posterior brain regions including bilateral parahippocampal gyrus and inferior temporal gyrus. Focal spontaneous hypofunction, as assessed by ALFF, correlates with epilepsy duration in patients with PNH-related epilepsy. Abnormalities existed both within the default-mode network and then across the whole brain, demonstrating that intrinsic brain dysfunction may be related to specific network interactions. Our findings provide novel understanding of the connectivity-based pathophysiological mechanisms of PNH.

Post-traumatic stress influences local and remote functional connectivity: a resting-state functional magnetic resonance imaging study.

Post-traumatic stress disorder (PTSD) is associated with alterations in regional brain activation and remote functional connectivity (FC) in limbic and prefrontal cortex. However, little is known about local FC changes following a traumatic event. Resting-state functional magnetic resonance images were collected for typhoon survivors with (n=27) and without PTSD (n=33), and healthy controls (n=30). Local FC was examined by calculating regional homogeneity (ReHo), and remote FC was investigated between regions showing significant ReHo group differences. The PTSD group showed ReHo changes in multiple regions, including the amygdala, parahippocampal gyrus, and prefrontal cortex relative to both control groups. Compared with healthy controls, typhoon survivors had increased ReHo in the insula/inferior frontal gyrus, middle and dorsal anterior cingulate cortex (MCC/dACC), as well as enhanced negative FC between the MCC/dACC and posterior cingulate cortex (PCC)/precuneus. The typhoon-exposed control group exhibited higher ReHo in the PCC/precuneus than the PTSD and healthy control groups. Furthermore, positive correlations were found between PTSD symptom severity and ReHo in several regions. Post-traumatic stress can influence local and remote FC, irrespective of PTSD diagnosis. Future studies are needed to validate the findings and to determine whether the alterations represent pre-existing or acquired deficits.

Altered Intrinsic Regional Activity and Interregional Functional Connectivity in Post-stroke Aphasia.

Several neuroimaging studies have examined cerebral function in patients who suffer from aphasia, but the mechanism underlying this disorder remains poorly understood. In this study, we examined alterations in the local regional and remote interregional network cerebral functions in aphasia combined with amplitude of low-frequency fluctuations and interregional functional connectivity (FC) using resting-state functional magnetic resonance imaging. A total of 17 post-stroke aphasic patients, all having suffered a stroke in the left hemisphere, as well as 20 age- and sex-matched healthy controls, were enrolled in this study. The aphasic patients showed significantly increased intrinsic regional activity mainly in the contralesional mesial temporal (hippocampus/parahippocampus, [HIP/ParaHIP]) and lateral temporal cortices. In addition, intrinsic regional activity in the contralesional HIP/ParaHIP was negatively correlated with construction score. Aphasic patients showed increased remote interregional FC between the contralesional HIP/ParaHIP and fusiform gyrus, but reduced FC in the ipsilesional occipital and parietal cortices. These findings suggested that the intrinsic regional brain dysfunctions in aphasia were related to interregional functional connectivity. Changes in the intrinsic regional brain activity and associated remote functional connectivity pattern would provide valuable information to enhance the understanding of the pathophysiological mechanisms of aphasia.

Methadone Restores Local and Remote Eeg Functional Connectivity in Opioid-Dependent Patients

Currently it has been proposed that normal brain function is critically dependent upon a dynamical balance between functions of local neuronal assemblies and global integrative processes. A loss of such metastable balance in favor of either independent or hyper-ordered processing is considered as the reflection of a brain disease. It has been shown that opioid dependence can be characterized as a disease of brain metastable balance, wherein local functional connectivity (synchronicity within neuronal assemblies) increased and remote functional connectivity (synchronicity between neuronal assemblies) decreased. Since methadone may be used as a maintenance treatment for opioid-dependent patients, the aim of this research was to study how methadone would influence the temporal and metastable cortical organization through the measures of local and remote electroencephalogram (EEG) functional connectivity in six opioid-depended patients who manage to complete at least six-month methadone treatment. The present study demonstrated that average parameters of temporal and metastable organization of the cortical dynamics (indexed by local and remote EEG functional connectivity) in such opioid-dependent patients did not differ from normal values of healthy subjects. We interpret these findings as a capability of the methadone to restore a normal temporal and metastable structure of brain activity in opioid-dependent patients after many months of methadone treatment. To our knowledge, present preliminary study is the first where the influence of methadone on temporal and metastable structure of EEG activity is demonstrated.

Opioid withdrawal results in an increased local and remote functional connectivity at EEG alpha and beta frequency bands

Withdrawal may be a natural model to study craving and compulsive drug seeking, since craving can be viewed as a conditioned dysphoric state. It has been suggested that functional connectivity between brain areas may be of major value in explaining excessive craving and compulsive drug seeking by providing essential link between psychological and biological processes. Considering that withdrawal initiates a widespread activation of cortical regions responsible for compulsive drug seeking and desire for the drug, we predict that withdrawal would result in a significant increase in functional cortical connectivity. We applied the novel operational architectonics approach that enables us to estimate both local and remote functional cortical connectivity by means of EEG structural synchrony measure. In 13 withdrawal opioid-dependent patients we found the evidence that local and remote cortical functional connectivity was indeed significantly enhanced (for both alpha and beta frequency oscillations). Additionally, statistical relationship between functional connectivity and the severity of opioid withdrawal has been found.

Cortex functional connectivity as a neurophysiological correlate of hypnosis: An EEG case study

Cortex functional connectivity associated with hypnosis was investigated in a single highly hypnotizable subject in a normal baseline condition and under neutral hypnosis during two sessions separated by a year. After the hypnotic induction, but without further suggestions as compared to the baseline condition, all studied parameters of local and remote functional connectivity were significantly changed. The significant differences between hypnosis and the baseline condition were observable (to different extent) in five studied independent frequency bands (delta, theta, alpha, beta, and gamma). The results were consistent and stable after 1 year. Based on these findings we conclude that alteration in functional connectivity of the brain may be regarded as a neuronal correlate of hypnosis (at least in very highly hypnotizable subjects) in which separate cognitive modules and subsystems may be temporarily incapable of communicating with each other normally.

Increased local and decreased remote functional connectivity at EEG alpha and beta frequency bands in opioid-dependent patients

Although researchers now have a working knowledge of key brain structures involved in realization of actions of substance abuse and addiction, deeper understanding will require examination of network interactions between cortical neuronal assemblies and their subcortical tails in the effects of opioid dependence. Given that repeated exposure to opiates initiates a widespread reorganization of cortical regions, we predict that opioid dependence would result in a considerable reorganization of local and remote functional connectivity in the neocortex. We applied the novel operational architectonics approach that enables us to estimate two local and remote functional cortex connectivities by means of electroencephalogram structural synchrony measure. In 22 opioid-dependent patients, we found the evidence that brain functional connectivity was indeed disrupted by chronic opioid abuse (i.e., the local functional connectivity increased and remote functional connectivity decreased in opioid abusers). This significant difference between "opioid" and "control" populations was the same for alpha and beta frequency bands. Additionally, significant negative relations between duration (years) of daily opioid abuse and the number/strength of functional connections in the posterior section of the cortex were found.

Local and remote functional connectivity of neocortex under the inhibition influence

The current paper focuses on a relatively new and promising area of the study of EEG transformations during brain information processing based on the reduction of the signal to the discrete quasi-stationary segment sequences which may reflect individual brain microstates or discrete operations. In this framework, the complex brain functions require integration of several operations throughout the whole neocortex. However, the role of inhibitory brain systems in such processes is still unsettled. The effects of a single dose (30 μg/kg) of lorazepam on the operational activity of neuronal populations and on the temporal binding between them were examined in a double-blind randomized crossover placebo-controlled study with eight healthy volunteers. EEG measures at 20 channels were evaluated on two occasions: (1) eyes closed, (2) eyes open. In short, we conducted a two-by-two factorial study where one factor manipulated GABA ergic neurotransmission (lorazepam vs. placebo), and the other factor was simply brain state (eyes closed vs. eyes opened). We were primarily interested in the main effect of lorazepam. In the present study, a connection between the mesoscopic level, described by the local functional processes (neuronal assemblies or populations) and the macroscopic level, described as a sequence of metastable brain states (remote functionally synchronized neuronal populations) was established. The role of inhibitory brain systems facilitated by lorazepam in the operational dynamics of neuronal populations and in the process of EEG structural synchrony (SS) (topological peculiarities) was addressed for the first time. It was shown that GABA signaling reorganized the dynamics of local neuronal populations and the remote functional connectivity between them.