Mechanisms underlying fatigue: a voxel-based morphometric study of chronic fatigue syndrome

Okada, Tomohisa; Tanaka, Masaaki; Kuratsune, Hirohiko; Watanabe, Yasuyoshi; Sadato, Norihiro

doi:10.1186/1471-2377-4-14

Cited by 187 publications

(174 citation statements)

References 26 publications

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“…Although most VBM processing and analysis is automated in SPM, several methodological options remain for user specification,19 especially in analysis of longitudinal image data. Inconsistent VBM findings in CFS patients in previous studies6, 7, 12, 14 motivated us here to validate segmentation and optimize VBM methodology. The VBM atrophy simulation experiment demonstrated (1) that normalization to a study specific template performs better than direct normalization to the default template provided in SPM12; (2) when the sample size is small, a random effects one‐sample t‐test of longitudinal difference images, either by means of the Jacobian difference method or the direct difference between different time points, has higher sensitivity than a paired t‐test of images from two time points; (3) that creation of a single image representative of the two time points (within‐subject template) for the purpose of the shared final spatial normalization should involve similar normalizations of both raw images and the same processing steps.…”

Section: Discussionmentioning

confidence: 86%

“…Although the cause of CFS remains unknown, altered central nervous system (CNS) function is believed to play an important role,4 including altered perception of fatigue and pain, deficits in the cognitive functions of concentration and memory, mood changes of depression and anxiety, and sleep disturbance 1. Accordingly, neuroimaging studies have investigated possible brain changes associated with CFS 5, 6, 7, 8. However, most of the previous neuroimaging studies were cross sectional comparisons of differences between CFS patients and normal controls (NCs) except one longitudinal study that examined white matter (WM) hyperintensities, cerebral blood and cerebrospinal fluid (CSF) flows in scans 1 year apart 9…”

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confidence: 99%

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Progressive brain changes in patients with chronic fatigue syndrome: A longitudinal MRI study

Shan

Kwiatek

Burnet

et al. 2016

Magnetic Resonance Imaging

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PurposeTo examine progressive brain changes associated with chronic fatigue syndrome (CFS).Materials and MethodsWe investigated progressive brain changes with longitudinal MRI in 15 CFS and 10 normal controls (NCs) scanned twice 6 years apart on the same 1.5 Tesla (T) scanner. MR images yielded gray matter (GM) volumes, white matter (WM) volumes, and T1‐ and T2‐weighted signal intensities (T1w and T2w). Each participant was characterized with Bell disability scores, and somatic and neurological symptom scores. We tested for differences in longitudinal changes between CFS and NC groups, inter group differences between pooled CFS and pooled NC populations, and correlations between MRI and symptom scores using voxel based morphometry. The analysis methodologies were first optimized using simulated atrophy.ResultsWe found a significant decrease in WM volumes in the left inferior fronto‐occipital fasciculus (IFOF) in CFS while in NCs it was unchanged (family wise error adjusted cluster level P value, P FWE < 0.05). This longitudinal finding was consolidated by the group comparisons which detected significantly decreased regional WM volumes in adjacent regions (P FWE < 0.05) and decreased GM and blood volumes in contralateral regions (P FWE < 0.05). Moreover, the regional GM and WM volumes and T2w in those areas showed significant correlations with CFS symptom scores (P FWE < 0.05).ConclusionThe results suggested that CFS is associated with IFOF WM deficits which continue to deteriorate at an abnormal rate. J. Magn. Reson. Imaging 2016;44:1301–1311.

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Section: Discussionmentioning

confidence: 86%

mentioning

confidence: 99%

Progressive brain changes in patients with chronic fatigue syndrome: A longitudinal MRI study

Shan

Kwiatek

Burnet

et al. 2016

Magnetic Resonance Imaging

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“…This model is consistent with other fatiguing disorders as well, because of their pathogenesis in the cortico-striato-thalamic circuit. Brain-imaging studies revealed involvement of the prefrontal cortex in patients with chronic fatigue syndrome [36], and in the prefrontal cortex and thalamus in patients with fatigue associated with multiple sclerosis [37]. Abnormal metabolic findings have also been reported in the prefrontal cortex and basal ganglia (putamen) in patients with fatigue and multiple sclerosis [38].…”

Section: Discussionmentioning

confidence: 96%

Perceptions of effort during handgrip and tongue elevation in Parkinson's disease

Solomon

Robin

2005

Parkinsonism & Related Disorders

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Background-Fatigue and the accompanying perception of effort are often heightened in Parkinson's disease.Objectives-To compare performance on three sense-of-effort tasks between patients with PD and matched neurologically normal control subjects.Methods-Sixteen PD subjects and 16 normal subjects performed three tasks to assess sense of effort: self-ratings of effort using direct-magnitude estimation, generating pressures at various levels of effort, and sustaining a submaximal level of effort. The latter two tasks were done with handgrip and tongue elevation.Results-Two of the three tasks successfully differentiated the groups. Subjects with PD provided significantly higher ratings of effort for general daily activities and for speech. During the constant-effort task, pressure curves decayed more rapidly for the PD subjects.Conclusions-Performance by PD subjects on the constant-effort task resembled that by normal adults who were pre-fatigued in previous experiments. Results support greater than normal senseof-effort related to fatigue in PD, and provide preliminary validation of a performance-based physiologic task to assess abnormal sense of effort in this population.

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“…Using these methods, both global searches (with no a priori hypotheses) and directed searches were performed in regions predicted to show anatomical changes. Based on regions shown to have anatomical changes in other voxel-based morphometry studies of chronic pain conditions (Apkarian et al, 2004;Schmidt-Wilcke et al, 2005 and stress-related disorders, including chronic fatigue syndrome and post-traumatic stress disorder (Villarreal et al, 2002;Okada et al, 2004;Chen et al, 2006), directed searches were performed in anterior, mid, and posterior cingulate cortex, insular cortex, dorsolateral prefrontal cortex, medial prefrontal cortex, and the parahippocampal gyrus.…”

Section: Discussionmentioning

confidence: 99%

“…Changes in brain morphology have been described in chronic pain conditions (Apkarian et al, 2004;Schmidt-Wilcke et al, 2005, chronic fatigue syndrome (Okada et al, 2004;de Lange et al, 2005), and posttraumatic stress disorder (Villarreal et al, 2002;Corbo et al, 2005;Chen et al, 2006). Because fibromyalgia shares commonalities with these disorders, we hypothesized that fibromyalgia might be associated with neuroanatomical abnormalities as well.…”

Section: Introductionmentioning

confidence: 99%

Accelerated Brain Gray Matter Loss in Fibromyalgia Patients: Premature Aging of the Brain?

Kuchinad

Schweinhardt²,

Seminowicz³

et al. 2007

J. Neurosci.

537

361

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Fibromyalgia is an intractable widespread pain disorder that is most frequently diagnosed in women. It has traditionally been classified as either a musculoskeletal disease or a psychological disorder. Accumulating evidence now suggests that fibromyalgia may be associated with CNS dysfunction. In this study, we investigate anatomical changes in the brain associated with fibromyalgia. Using voxel-based morphometric analysis of magnetic resonance brain images, we examined the brains of 10 female fibromyalgia patients and 10 healthy controls. We found that fibromyalgia patients had significantly less total gray matter volume and showed a 3.3 times greater ageassociated decrease in gray matter than healthy controls. The longer the individuals had had fibromyalgia, the greater the gray matter loss, with each year of fibromyalgia being equivalent to 9.5 times the loss in normal aging. In addition, fibromyalgia patients demonstrated significantly less gray matter density than healthy controls in several brain regions, including the cingulate, insular and medial frontal cortices, and parahippocampal gyri. The neuroanatomical changes that we see in fibromyalgia patients contribute additional evidence of CNS involvement in fibromyalgia. In particular, fibromyalgia appears to be associated with an acceleration of age-related changes in the very substance of the brain. Moreover, the regions in which we demonstrate objective changes may be functionally linked to core features of the disorder including affective disturbances and chronic widespread pain.

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Mechanisms underlying fatigue: a voxel-based morphometric study of chronic fatigue syndrome

Abstract: Background: Fatigue is a crucial sensation that triggers rest, yet its underlying neuronal mechanisms remain unclear. Intense long-term fatigue is a symptom of chronic fatigue syndrome, which is used as a model to study the mechanisms underlying fatigue.

Cited by 187 publications

References 26 publications

Progressive brain changes in patients with chronic fatigue syndrome: A longitudinal MRI study

Progressive brain changes in patients with chronic fatigue syndrome: A longitudinal MRI study

Perceptions of effort during handgrip and tongue elevation in Parkinson's disease

Accelerated Brain Gray Matter Loss in Fibromyalgia Patients: Premature Aging of the Brain?

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