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      A brain MRI study of chronic fatigue syndrome: evidence of brainstem dysfunction and altered homeostasis

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          Abstract

          To explore brain involvement in chronic fatigue syndrome (CFS), the statistical parametric mapping of brain MR images has been extended to voxel-based regressions against clinical scores. Using SPM5 we performed voxel-based morphometry (VBM) and analysed T 1- and T 2-weighted spin-echo MR signal levels in 25 CFS subjects and 25 normal controls (NC). Clinical scores included CFS fatigue duration, a score based on the 10 most common CFS symptoms, the Bell score, the hospital anxiety and depression scale (HADS) anxiety and depression, and hemodynamic parameters from 24-h blood pressure monitoring. We also performed group × hemodynamic score interaction regressions to detect locations where MR regressions were opposite for CFS and NC, thereby indicating abnormality in the CFS group. In the midbrain, white matter volume was observed to decrease with increasing fatigue duration. For T 1-weighted MR and white matter volume, group × hemodynamic score interactions were detected in the brainstem [strongest in midbrain grey matter (GM)], deep prefrontal white matter (WM), the caudal basal pons and hypothalamus. A strong correlation in CFS between brainstem GM volume and pulse pressure suggested impaired cerebrovascular autoregulation. It can be argued that at least some of these changes could arise from astrocyte dysfunction. These results are consistent with an insult to the midbrain at fatigue onset that affects multiple feedback control loops to suppress cerebral motor and cognitive activity and disrupt local CNS homeostasis, including resetting of some elements of the autonomic nervous system (ANS). © 2011 The Authors. NMR in Biomedicine published by John Wiley & Sons, Ltd.

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          Most cited references61

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          Controlling the False Discovery Rate: A Practical and Powerful Approach to Multiple Testing

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            Glial regulation of the cerebral microvasculature.

            The brain is a heterogeneous organ with regionally varied and constantly changing energetic needs. Blood vessels in the brain are equipped with control mechanisms that match oxygen and glucose delivery through blood flow with the local metabolic demands that are imposed by neural activity. However, the cellular bases of this mechanism have remained elusive. A major advance has been the demonstration that astrocytes, cells with extensive contacts with both synapses and cerebral blood vessels, participate in the increases in flow evoked by synaptic activity. Their organization in nonoverlapping spatial domains indicates that they are uniquely positioned to shape the spatial distribution of the vascular responses that are evoked by neural activity. Astrocytic calcium is an important determinant of microvascular function and may regulate flow independently of synaptic activity. The involvement of astrocytes in neurovascular coupling has broad implications for the interpretation of functional imaging signals and for the understanding of brain diseases that are associated with neurovascular dysfunction.
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              Brain correlates of autonomic modulation: combining heart rate variability with fMRI.

              The central autonomic network (CAN) has been described in animal models but has been difficult to elucidate in humans. Potential confounds include physiological noise artifacts affecting brainstem neuroimaging data, and difficulty in deriving non-invasive continuous assessments of autonomic modulation. We have developed and implemented a new method which relates cardiac-gated fMRI timeseries with continuous-time heart rate variability (HRV) to estimate central autonomic processing. As many autonomic structures of interest are in brain regions strongly affected by cardiogenic pulsatility, we chose to cardiac-gate our fMRI acquisition to increase sensitivity. Cardiac-gating introduces T1-variability, which was corrected by transforming fMRI data to a fixed TR using a previously published method [Guimaraes, A.R., Melcher, J.R., et al., 1998. Imaging subcortical auditory activity in humans. Hum. Brain Mapp. 6(1), 33-41]. The electrocardiogram was analyzed with a novel point process adaptive-filter algorithm for computation of the high-frequency (HF) index, reflecting the time-varying dynamics of efferent cardiovagal modulation. Central command of cardiovagal outflow was inferred by using the resample HF timeseries as a regressor to the fMRI data. A grip task was used to perturb the autonomic nervous system. Our combined HRV-fMRI approach demonstrated HF correlation with fMRI activity in the hypothalamus, cerebellum, parabrachial nucleus/locus ceruleus, periaqueductal gray, amygdala, hippocampus, thalamus, and dorsomedial/dorsolateral prefrontal, posterior insular, and middle temporal cortices. While some regions consistent with central cardiovagal control in animal models gave corroborative evidence for our methodology, other mostly higher cortical or limbic-related brain regions may be unique to humans. Our approach should be optimized and applied to study the human brain correlates of autonomic modulation for various stimuli in both physiological and pathological states.
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                Author and article information

                Journal
                NMR Biomed
                NMR Biomed
                nbm
                Nmr in Biomedicine
                John Wiley & Sons, Ltd (Chichester, UK )
                0952-3480
                1099-1492
                December 2011
                11 May 2011
                : 24
                : 10
                : 1302-1312
                Affiliations
                [a ]Department of Nuclear Medicine, The Queen Elizabeth Hospital Adelaide, South Australia
                [b ]School of Chemistry and Physics, University of Adelaide Adelaide, South Australia
                [c ]Division of Medicine, Lyell McEwin Hospital Adelaide, South Australia
                [d ]Endocrinology Department, Royal Adelaide Hospital Adelaide, South Australia
                [e ]Department of Radiology, The Queen Elizabeth Hospital Adelaide, South Australia
                [f ]Physiology Department, University of South Australia Adelaide, South Australia
                [g ]Adelaide Western General Practice Network Adelaide, South Australia
                Author notes
                * Leighton Barnden, Department of Nuclear Medicine, The Queen Elizabeth Hospital, Woodville, SA 5011, Australia., E-mail Leighton.Barnden@ 123456health.sa.gov.au

                The copyright line for this article was changed on 23 February 2015 after original online publication.

                Article
                10.1002/nbm.1692
                4369126
                21560176
                9ef6c80b-1451-46e9-9ee7-83b80a306f0a
                © 2011 The Authors. NMR in Biomedicine published by John Wiley & Sons, Ltd.

                This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

                History
                : 24 September 2010
                : 21 January 2011
                : 24 January 2011
                Categories
                Research Articles

                Radiology & Imaging
                voxel based,cfs,mri,regression,interaction,brainstem,homeostasis,autonomic nervous system
                Radiology & Imaging
                voxel based, cfs, mri, regression, interaction, brainstem, homeostasis, autonomic nervous system

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