Caffeine-Induced Global Reductions in Resting-State BOLD Connectivity Reflect Widespread Decreases in MEG Connectivity.

In resting-state functional magnetic resonance imaging (fMRI), the temporal correlation between spontaneous fluctuations of the blood oxygenation level dependent (BOLD) signal from different brain regions is used to assess functional connectivity. However, because the BOLD signal is an indirect measure of neuronal activity, its complex hemodynamic nature can complicate the interpretation of differences in connectivity that are observed across conditions or subjects. For example, prior studies have shown that caffeine leads to widespread reductions in BOLD connectivity but were not able to determine if neural or vascular factors were primarily responsible for the observed decrease. In this study, we used source-localized magnetoencephalography (MEG) in conjunction with fMRI to further examine the origins of the caffeine-induced changes in BOLD connectivity. We observed widespread and significant (p < 0.01) reductions in both MEG and fMRI connectivity measures, suggesting that decreases in the connectivity of resting-state neuro-electric power fluctuations were primarily responsible for the observed BOLD connectivity changes. The MEG connectivity decreases were most pronounced in the beta band. By demonstrating the similarity in MEG and fMRI based connectivity changes, these results provide evidence for the neural basis of resting-state fMRI networks and further support the potential of MEG as a tool to characterize resting-state connectivity

Fractal analysis of resting state functional connectivity of the brain

A variety of resting state neuroimaging data tend to exhibit fractal behavior where its power spectrum follows power-law scaling. Resting state functional connectivity is significantly influenced by fractal behavior which may not directly originate from neuronal population activities of the brain. To describe the fractal behavior, we adopted the fractionally integrated process (FIP) model instead of the fractional Gaussian noise (FGN) since the FIP model covers more general aspects of fractality than the FGN model. We also introduce a novel concept called the nonfractal connectivity which is defined as the correlation of short memory independent of fractal behavior, and compared it with the fractal connectivity which is an asymptotic wavelet correlation. We propose several wavelet-based estimators of fractal connectivity and nonfractal connectivity for a multivariate fractionally integrated noise (mFIN). The performance of these estimators was evaluated through simulation studies and the analyses of resting state functional MRI data of the rat brain.Comment: The 2012 International Joint Conference on Neural Network

The Role of Corpus Callosum Development in Functional Connectivity and Cognitive Processing

The corpus callosum is hypothesized to play a fundamental role in integrating information and mediating complex behaviors. Here, we demonstrate that lack of normal callosal development can lead to deficits in functional connectivity that are related to impairments in specific cognitive domains. We examined resting-state functional connectivity in individuals with agenesis of the corpus callosum (AgCC) and matched controls using magnetoencephalographic imaging (MEG-I) of coherence in the alpha (8–12 Hz), beta (12–30 Hz) and gamma (30–55 Hz) bands. Global connectivity (GC) was defined as synchronization between a region and the rest of the brain. In AgCC individuals, alpha band GC was significantly reduced in the dorsolateral pre-frontal (DLPFC), posterior parietal (PPC) and parieto-occipital cortices (PO). No significant differences in GC were seen in either the beta or gamma bands. We also explored the hypothesis that, in AgCC, this regional reduction in functional connectivity is explained primarily by a specific reduction in interhemispheric connectivity. However, our data suggest that reduced connectivity in these regions is driven by faulty coupling in both inter- and intrahemispheric connectivity. We also assessed whether the degree of connectivity correlated with behavioral performance, focusing on cognitive measures known to be impaired in AgCC individuals. Neuropsychological measures of verbal processing speed were significantly correlated with resting-state functional connectivity of the left medial and superior temporal lobe in AgCC participants. Connectivity of DLPFC correlated strongly with performance on the Tower of London in the AgCC cohort. These findings indicate that the abnormal callosal development produces salient but selective (alpha band only) resting-state functional connectivity disruptions that correlate with cognitive impairment. Understanding the relationship between impoverished functional connectivity and cognition is a key step in identifying the neural mechanisms of language and executive dysfunction in common neurodevelopmental and psychiatric disorders where disruptions of callosal development are consistently identified

Thalamo-cortical network activity between migraine attacks. Insights from MRI-based microstructural and functional resting-state network correlation analysis

BACKGROUND: Resting state magnetic resonance imaging allows studying functionally interconnected brain networks. Here we were aimed to verify functional connectivity between brain networks at rest and its relationship with thalamic microstructure in migraine without aura (MO) patients between attacks. METHODS: Eighteen patients with untreated MO underwent 3 T MRI scans and were compared to a group of 19 healthy volunteers (HV). We used MRI to collect resting state data among two selected resting state networks, identified using group independent component (IC) analysis. Fractional anisotropy (FA) and mean diffusivity (MD) values of bilateral thalami were retrieved from a previous diffusion tensor imaging study on the same subjects and correlated with resting state ICs Z-scores. RESULTS: In comparison to HV, in MO we found significant reduced functional connectivity between the default mode network and the visuo-spatial system. Both HV and migraine patients selected ICs Z-scores correlated negatively with FA values of the thalamus bilaterally. CONCLUSIONS: The present results are the first evidence supporting the hypothesis that an abnormal resting within networks connectivity associated with significant differences in baseline thalamic microstructure could contribute to interictal migraine pathophysiology

Association between resting-state functional connectivity, glucose metabolism and task-related activity of neural networks

The brain is organized into several large-scale functional networks. Such networks are primarily characterized by intrinsic functional connectivity, i.e. temporally synchronous activity between the different brain regions of a network. The functional connectivity of networks can be identified via functional MRI during resting state, i.e. without engaging the subject in a particular task. Resting-state fMRI is thus less demanding on the subject and therefore of particular interest from a clinical point of view to detect alterations in brain function. Applied to neurodegenerative disease including Alzheimer’s disease, resting-state fMRI has shown alterations in several resting-state networks, suggesting that basic network function is altered in AD. However, the interpretation of alterations in resting-state fMRI connectivity is inherently limited since no cognitive states are explicitly expressed during fMRI. In this regard, we aimed to elucidate how resting-state fMRI connectivity relates to 1) cognition-related brain activity and 2) markers of pathologically altered brain function in AD. In order to understand at a more basic level the association between resting-state and task-related fMRI, we first examined, in a group of elderly healthy subjects, the association between functional connectivity of major networks assessed during resting-state fMRI with those acquired during memory-task related fMRI, in the same individuals. Secondly, in order to assess whether alterations in AD are associated with already well-established markers of pathological brain function in AD, we compared resting-state fMRI functional network connectivity with that in FDG-PET metabolism in AD. Project 1: We investigated the association between functional connectivity acquired during rest and the level of activation obtained during an episodic memory task that included the encoding and forced-choice recognition of face-name pairs in elderly cognitively normal subjects. Independent component analysis (ICA) was used to identify major resting-state networks in the brain. Next, we applied ICA to the task-fMRI data to determine the components (networks) that were significantly associated with the task regressors of successful vs unsuccessful learning or recognition trials. Spatial correlation analysis between the resulting extracted resting-state and task-related fMRI components showed a spatial match in several components such as medial temporal lobe centered components and posterior components. However, apart from the spatial correspondence, the level of resting state functional connectivity did not predict the level of task-related functional connectivity in spatially matching components. Together these results suggested that particular resting-state networks are activated during a memory task, however, the level of baseline connectivity does not predict to what extent a network becomes activated during a task. Future studies may assess whether pathological resting-state connectivity predicts altered task-related connectivity in the same networks in AD. Project 2: We examined the association between resting-state fMRI functional connectivity within major functional networks and FDG-PET metabolism in those networks, assessed in elderly healthy controls, subjects with prodromal AD (mild cognitive impairment and amyloid PET biomarker confirmed AD etiology) and AD dementia. We found that FDG-PET was generally reduced in all networks in the course of AD. The main finding was that lower network functional connectivity was associated with lower FDG-PET uptake in the Default mode network and fronto-parietal attention network across the whole group and specifically in prodromal AD, suggesting that both modalities are associated in higher networks affected in the course of AD. These results provide insightful comprehension of the hypometabolism patterns that are typically found in AD

An approach for identifying brainstem dopaminergic pathways using resting state functional MRI.

Here, we present an approach for identifying brainstem dopaminergic pathways using resting state functional MRI. In a group of healthy individuals, we searched for significant functional connectivity between dopamine-rich midbrain areas (substantia nigra; ventral tegmental area) and a striatal region (caudate) that was modulated by both a pharmacological challenge (the administration of the dopaminergic agonist bromocriptine) and a dopamine-sensitive cognitive trait (an individual's working memory capacity). A significant inverted-U shaped connectivity pattern was found in a subset of midbrain-striatal connections, demonstrating that resting state fMRI data is sufficiently powerful to identify brainstem neuromodulatory brain networks

Lewy body compared with Alzheimer dementia is associated with decreased functional connectivity in resting state networks.

Resting state functional magnetic resonance imaging (fMRI) was used to measure whole brain functional connectivity within specific networks hypothesised to be more affected in dementia with Lewy bodies (DLB) (a disease characterised by prominent attentional deficits, spontaneous motor features of parkinsonism and depression) than in Alzheimer׳s disease (AD) and controls. This study involved 68 subjects (15 DLB, 13 AD and 40 controls) who were scanned using resting state BOLD (blood-oxygen-level-dependent) fMRI on a 3T MRI scanner. Functional connectivity was measured using a model-free independent component analysis approach that consisted of temporally concatenating the resting state fMRI data of all study subjects and investigating group differences using a back-reconstruction procedure. Resting state functional connectivity was affected in the default mode, salience, executive and basal ganglia networks in DLB subjects compared with AD and controls. Functional connectivity was lower in DLB compared with AD and controls in these networks, except for the basal ganglia network, where connectivity was greater in DLB. No resting state networks showed less connectivity in AD compared with DLB or controls. Our results suggest that functional connectivity of resting state networks can identify differences between DLB and AD subjects that may help to explain why DLB subjects have more frequent attentional deficits, parkinsonian symptoms, and depression than those with AD.North East Dementia and Neurodegenerative Diseases Research Network (DeNDRoN)This is the author accepted manuscript. The final version is available from Elsevier via http://dx.doi.org/10.1016/j.pscychresns.2014.06.00

Functional connectivity changes and their relationship with clinical disability and white matter integrity in patients with relapsing-remitting multiple sclerosis

Background and objective: To define the pathological substrate underlying disability in multiple sclerosis by evaluating the relationship of resting-state functional connectivity with microstructural brain damage, as assessed by diffusion tensor maging, and clinical impairments. Methods: Thirty relapsing–remitting patients and 24 controls underwent 3T-MRI; motor abilities were evaluated by using measures of walking speed, hand dexterity and balance capability, while information processing speed was evaluated by a paced auditory serial addiction task. Independent component analysis and tract-based spatial statistics were applied to RS-fMRI and diffusion tensor imaging data using FSL software. Group differences, after dual regression, and clinical correlations were modelled with GeneralLinear-Model and corrected for multiple comparisons. Results: Patients showed decreased functional connectivity in 5 of 11 resting-state-networks (cerebellar, executive-control, medial-visual, basal ganglia and sensorimotor), changes in inter-network correlations and widespread white matter microstructural damage. In multiple sclerosis, corpus callosum microstructural damage positively correlated with functional connectivity in cerebellar and auditory networks. Moreover, functional connectivity within the medial-visual network inversely correlated with information processing speed. White matter widespread microstructural damage inversely correlated with both the paced auditory serial addiction task and hand dexterity. Conclusions: Despite the within-network functional connectivity decrease and the widespread microstructural damage, the inter-network functional connectivity changes suggest a global brain functional rearrangement in multiple sclerosis. The correlation between functional connectivity alterations and callosal damage uncovers a link between functional and structural connectivity. Finally, functional connectivity abnormalities affect information processing speed rather than motor abilities

Centralized and distributed cognitive task processing in the human connectome

A key question in modern neuroscience is how cognitive changes in a human brain can be quantified and captured by functional connectomes (FC) . A systematic approach to measure pairwise functional distance at different brain states is lacking. This would provide a straight-forward way to quantify differences in cognitive processing across tasks; also, it would help in relating these differences in task-based FCs to the underlying structural network. Here we propose a framework, based on the concept of Jensen-Shannon divergence, to map the task-rest connectivity distance between tasks and resting-state FC. We show how this information theoretical measure allows for quantifying connectivity changes in distributed and centralized processing in functional networks. We study resting-state and seven tasks from the Human Connectome Project dataset to obtain the most distant links across tasks. We investigate how these changes are associated to different functional brain networks, and use the proposed measure to infer changes in the information processing regimes. Furthermore, we show how the FC distance from resting state is shaped by structural connectivity, and to what extent this relationship depends on the task. This framework provides a well grounded mathematical quantification of connectivity changes associated to cognitive processing in large-scale brain networks.Comment: 22 pages main, 6 pages supplementary, 6 figures, 5 supplementary figures, 1 table, 1 supplementary table. arXiv admin note: text overlap with arXiv:1710.0219

Abnormal resting-state functional connectivity in progressive supranuclear palsy and corticobasal syndrome

Background: Pathological and MRI-based evidence suggests that multiple brain structures are likely to be involved in functional disconnection between brain areas. Few studies have investigated resting-state functional connectivity (rsFC) in progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS). In this study, we investigated within- and between-network rsFC abnormalities in these two conditions. Methods: Twenty patients with PSP, 11 patients with CBS, and 16 healthy subjects (HS) underwent a resting-state fMRI study. Resting-state networks (RSNs) were extracted to evaluate within- and between-network rsFC using the Melodic and FSLNets software packages. results: Increased within-network rsFC was observed in both PSP and CBS patients, with a larger number of RSNs being involved in CBS. Within-network cerebellar rsFC positively correlated with mini-mental state examination scores in patients with PSP. Compared to healthy volunteers, PSP and CBS patients exhibit reduced functional connectivity between the lateral visual and auditory RSNs, with PSP patients additionally showing lower functional connectivity between the cerebellar and insular RSNs. Moreover, rsFC between the salience and executive-control RSNs was increased in patients with CBS compared to HS. conclusion: This study provides evidence of functional brain reorganization in both PSP and CBS. Increased within-network rsFC could represent a higher degree of synchronization in damaged brain areas, while between-network rsFC abnormalities may mainly reflect degeneration of long-range white matter fibers