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      L-DOPA changes spontaneous low-frequency BOLD signal oscillations in Parkinson's disease: a resting state fMRI study

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          Abstract

          Analysis of the amplitude of low frequency BOLD signal fluctuations (ALFF) in the resting state has recently been used to study the dynamics of intrinsic neural activity. Several studies have also suggested its potential as a biomarker for neuropsychiatric disease. In the current study, we quantified ALFF to determine changes in intrinsic neural oscillations in patients with Parkinson's disease (PD) on and off L-DOPA. Twenty-four PD patients and 24 healthy age-matched controls participated in the study. PD patients underwent two resting state fMRI sessions, either ON a controlled dose of L-DOPA or following a placebo pill (OFF). Control participants underwent one test session. We found that there was increased amplitude of low frequency BOLD signal oscillations for PD patients OFF L-DOPA in the primary and secondary motor areas, and in the middle and medial prefrontal cortices. L-DOPA significantly reduced the amplitude of low frequency oscillations within these regions. The degree of ALFF in the premotor cortex predicted patients' motor performance as measured by the Grooved Pegboard task, such that greater ALFF was associated with poorer performance. These results are in line with the pathophysiology of PD, which shows changes in neural oscillations. Thus, frequency domain analyses of resting state BOLD fMRI signals may provide a useful means to study the pathophysiology of PD and the physiology of the brain's dopaminergic pathways.

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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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            Intrinsic functional connectivity as a tool for human connectomics: theory, properties, and optimization.

            Resting state functional connectivity MRI (fcMRI) is widely used to investigate brain networks that exhibit correlated fluctuations. While fcMRI does not provide direct measurement of anatomic connectivity, accumulating evidence suggests it is sufficiently constrained by anatomy to allow the architecture of distinct brain systems to be characterized. fcMRI is particularly useful for characterizing large-scale systems that span distributed areas (e.g., polysynaptic cortical pathways, cerebro-cerebellar circuits, cortical-thalamic circuits) and has complementary strengths when contrasted with the other major tool available for human connectomics-high angular resolution diffusion imaging (HARDI). We review what is known about fcMRI and then explore fcMRI data reliability, effects of preprocessing, analysis procedures, and effects of different acquisition parameters across six studies (n = 98) to provide recommendations for optimization. Run length (2-12 min), run structure (1 12-min run or 2 6-min runs), temporal resolution (2.5 or 5.0 s), spatial resolution (2 or 3 mm), and the task (fixation, eyes closed rest, eyes open rest, continuous word-classification) were varied. Results revealed moderate to high test-retest reliability. Run structure, temporal resolution, and spatial resolution minimally influenced fcMRI results while fixation and eyes open rest yielded stronger correlations as contrasted to other task conditions. Commonly used preprocessing steps involving regression of nuisance signals minimized nonspecific (noise) correlations including those associated with respiration. The most surprising finding was that estimates of correlation strengths stabilized with acquisition times as brief as 5 min. The brevity and robustness of fcMRI positions it as a powerful tool for large-scale explorations of genetic influences on brain architecture. We conclude by discussing the strengths and limitations of fcMRI and how it can be combined with HARDI techniques to support the emerging field of human connectomics.
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              Neurophysiological investigation of the basis of the fMRI signal.

              Functional magnetic resonance imaging (fMRI) is widely used to study the operational organization of the human brain, but the exact relationship between the measured fMRI signal and the underlying neural activity is unclear. Here we present simultaneous intracortical recordings of neural signals and fMRI responses. We compared local field potentials (LFPs), single- and multi-unit spiking activity with highly spatio-temporally resolved blood-oxygen-level-dependent (BOLD) fMRI responses from the visual cortex of monkeys. The largest magnitude changes were observed in LFPs, which at recording sites characterized by transient responses were the only signal that significantly correlated with the haemodynamic response. Linear systems analysis on a trial-by-trial basis showed that the impulse response of the neurovascular system is both animal- and site-specific, and that LFPs yield a better estimate of BOLD responses than the multi-unit responses. These findings suggest that the BOLD contrast mechanism reflects the input and intracortical processing of a given area rather than its spiking output.
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                Author and article information

                Journal
                Front Syst Neurosci
                Front Syst Neurosci
                Front. Syst. Neurosci.
                Frontiers in Systems Neuroscience
                Frontiers Media S.A.
                1662-5137
                04 July 2012
                2012
                : 6
                : 52
                Affiliations
                [1] 1Neuroscience Program, University of Michigan, Ann Arbor MI, USA
                [2] 2Department of Biomedical Engineering, University of Michigan, Ann Arbor MI, USA
                [3] 3Department of Radiology, University of Michigan, Ann Arbor MI, USA
                [4] 4Department of Neurology, University of Michigan, Ann Arbor MI, USA
                [5] 5GRECC, VA Ann Arbor Healthcare System, University of Michigan, Ann Arbor MI, USA
                [6] 6School of Kinesiology, University of Michigan, Ann Arbor MI, USA
                [7] 7Department of Psychology, University of Michigan, Ann Arbor MI, USA
                [8] 8Institute of Gerontology, University of Michigan, Ann Arbor MI, USA
                Author notes

                Edited by: Jose Bargas, Universidad Nacional Autónoma de México, Mexico

                Reviewed by: Jose Bargas, Universidad Nacional Autónoma de México, Mexico; M. Gustavo Murer, Universidad de Buenos Aires, Argentina

                *Correspondence: Y. Kwak, Neuroscience Program, University of Michigan, 401 Washtenaw Ave., Ann Arbor, MI 48109-2214, USA. e-mail: youngbin.Kwak@ 123456duke.edu

                †Present address: Y. Kwak, Center for Cognitive Neuroscience, Levine Science Research Center, Duke University, Durham, NC 27708, USA.

                Article
                10.3389/fnsys.2012.00052
                3389385
                22783172
                8400fc28-7f3f-4226-9121-7af450d38f42
                Copyright © 2012 Kwak, Peltier, Bohnen, Müller, Dayalu and Seidler.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in other forums, provided the original authors and source are credited and subject to any copyright notices concerning any third-party graphics etc.

                History
                : 18 November 2011
                : 13 June 2012
                Page count
                Figures: 8, Tables: 5, Equations: 0, References: 68, Pages: 15, Words: 10918
                Categories
                Neuroscience
                Original Research Article

                Neurosciences
                parkinson's disease,neural oscillation,resting-state fmri,dopamine,bold signal
                Neurosciences
                parkinson's disease, neural oscillation, resting-state fmri, dopamine, bold signal

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