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      Clinical Applications of Resting State Functional Connectivity

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          Abstract

          During resting conditions the brain remains functionally and metabolically active. One manifestation of this activity that has become an important research tool is spontaneous fluctuations in the blood oxygen level-dependent (BOLD) signal of functional magnetic resonance imaging (fMRI). The identification of correlation patterns in these spontaneous fluctuations has been termed resting state functional connectivity (fcMRI) and has the potential to greatly increase the translation of fMRI into clinical care. In this article we review the advantages of the resting state signal for clinical applications including detailed discussion of signal to noise considerations. We include guidelines for performing resting state research on clinical populations, outline the different areas for clinical application, and identify important barriers to be addressed to facilitate the translation of resting state fcMRI into the clinical realm.

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          Altered baseline brain activity in children with ADHD revealed by resting-state functional MRI.

          In children with attention deficit hyperactivity disorder (ADHD), functional neuroimaging studies have revealed abnormalities in various brain regions, including prefrontal-striatal circuit, cerebellum, and brainstem. In the current study, we used a new marker of functional magnetic resonance imaging (fMRI), amplitude of low-frequency (0.01-0.08Hz) fluctuation (ALFF) to investigate the baseline brain function of this disorder. Thirteen boys with ADHD (13.0+/-1.4 years) were examined by resting-state fMRI and compared with age-matched controls. As a result, we found that patients with ADHD had decreased ALFF in the right inferior frontal cortex, [corrected] and bilateral cerebellum and the vermis as well as increased ALFF in the right anterior cingulated cortex, left sensorimotor cortex, and bilateral brainstem. This resting-state fMRI study suggests that the changed spontaneous neuronal activity of these regions may be implicated in the underlying pathophysiology in children with ADHD.
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            Spontaneous low-frequency BOLD signal fluctuations: an fMRI investigation of the resting-state default mode of brain function hypothesis.

            Recent neuroimaging studies have lead to the proposal that rest is characterized by an organized, baseline level of activity, a default mode of brain function that is suspended during specific goal-oriented mental activity. Previous studies have shown that the primary function subserved by the default mode is that of an introspectively oriented, self-referential mode of mental activity. The default mode of brain function hypothesis is readdressed from the perspective of the presence of low-frequency blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging (fMRI) signal changes (0.012-0.1 Hz) in the resting brain. The results show that the brain during rest is not tonically active in a single mode of brain function. Rather, the findings presented here suggest that the brain recurrently toggles between an introspectively oriented mode (default mode) and a state-of-mind that tentatively might be interpreted as an extrospectively oriented mode that involves a readiness and alertness to changes in the external and internal environment.
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              Separating respiratory-variation-related fluctuations from neuronal-activity-related fluctuations in fMRI.

              Subtle changes in a subject's breathing rate or depth, which occur naturally during rest at low frequencies (<0.1 Hz), have been shown to be significantly correlated with fMRI signal changes throughout gray matter and near large vessels. The goal of this study was to investigate the impact of these low-frequency respiration variations on both task activation fMRI studies and resting-state functional connectivity analysis. Unlike MR signal changes correlated with the breathing motion ( approximately 0.3 Hz), BOLD signal changes correlated with across-breath variations in respiratory volume ( approximately 0.03 Hz) appear localized to blood vessels and regions with high blood volume, such as gray matter, similar to changes seen in response to a breath-hold challenge. In addition, the respiration-variation-induced signal changes were found to coincide with many of the areas identified as part of the 'default mode' network, a set of brain regions hypothesized to be more active at rest. Regions could therefore be classified as being part of a resting network based on their similar respiration-induced changes rather than their synchronized neuronal activity. Monitoring and removing these respiration variations led to a significant improvement in the identification of task-related activation and deactivation and only slight differences in regions correlated with the posterior cingulate at rest. Regressing out global signal changes or cueing the subject to breathe at a constant rate and depth resulted in an improved spatial overlap between deactivations and resting-state correlations among areas that showed deactivation.
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                Author and article information

                Journal
                Front Syst Neurosci
                Front. Syst. Neurosci.
                Frontiers in Systems Neuroscience
                Frontiers Research Foundation
                1662-5137
                11 March 2010
                17 June 2010
                2010
                : 4
                : 19
                Affiliations
                [1] 1simplePartners Neurology Residency, Massachusetts General Hospital, Brigham and Women's Hospital, Harvard Medical School Boston, MA, USA
                [2] 2simpleDepartment of Neurology and Neurological Sciences, Stanford University School of Medicine Stanford, CA, USA
                Author notes

                Edited by: Lucina Q. Uddin, Stanford University, USA

                Reviewed by: F. Castellanos, Nathan Kline Institute, USA; New York University School of Medicine, USA; Yufeng Zang, Beijing Normal University, China

                *Correspondence: Michael D. Fox, Partners Neurology Residency, Massachusetts General Hospital, Brigham and Women's Hospital, Harvard Medical School, 55 Fruit St., Boston, MA 02114, USA. e-mail: foxmdphd@ 123456gmail.com
                Article
                10.3389/fnsys.2010.00019
                2893721
                20592951
                71d32375-5d25-41b8-b567-25a16684dade
                Copyright © 2010 Fox and Greicius.

                This is an open-access article subject to an exclusive license agreement between the authors and the Frontiers Research Foundation, which permits unrestricted use, distribution, and reproduction in any medium, provided the original authors and source are credited.

                History
                : 09 February 2010
                : 11 May 2010
                Page count
                Figures: 4, Tables: 2, Equations: 0, References: 137, Pages: 13, Words: 12068
                Categories
                Neuroscience
                Review Article

                Neurosciences
                psychiatric disease,spontaneous activity,brain,neurological disease,intrinsic activity,fmri,fcmri

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