Gray matter volume reduction in the chronic fatigue syndrome

Abstract

The chronic fatigue syndrome (CFS) is a disabling disorder of unknown etiology. The symptomatology of CFS (central fatigue, impaired concentration, attention and memory) suggests that this disorder could be related to alterations at the level of the central nervous system. In this study, we have used an automated and unbiased morphometric technique to test whether CFS patients display structural cerebral abnormalities. We mapped structural cerebral morphology and volume in two cohorts of CFS patients (in total 28 patients) and healthy controls (in total 28 controls) from high-resolution structural magnetic resonance images, using voxel-based morphometry. Additionally, we recorded physical activity levels to explore the relation between severity of CFS symptoms and cerebral abnormalities. We observed significant reductions in global gray matter volume in both cohorts of CFS patients, as compared to matched control participants. Moreover, the decline in gray matter volume was linked to the reduction in physical activity, a core aspect of CFS. These findings suggest that the central nervous system plays a key role in the pathophysiology of CFS and point to a new objective and quantitative tool for clinical diagnosis of this disabling disorder.

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

“…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.…”

“…One study found a decrease in regional GM volume in prefrontal areas,7 and another found such decreases in the occipital lobe, right angular gyrus, and left parahippocampal gyrus 12. Cortical thickness was found to be increased in right arcuate fasciculus end points, the middle temporal gyrus, precentral gyri, and occipital lobe,8 while other studies did not find significant regional GM differences 6, 11. Similarly, inconsistent WM changes have been reported 8, 11, 12, 13.…”

“…One group found significant reductions in global GM volumes6 while others did not 8, 11. One study found a decrease in regional GM volume in prefrontal areas,7 and another found such decreases in the occipital lobe, right angular gyrus, and left parahippocampal gyrus 12.…”

“…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…”

Associations between cognitive performance and pain in chronic fatigue syndrome: comorbidity with fibromyalgia does matter

“…Indeed, an overlap exists in components of the pain neuromatrix and brain regions involved in cognitive processing (e.g., anterior cingulate cortex, insular cortex, periaqueductal gray) (14). Together with the demonstrated changes in neuroplasticity [e.g., gray matter volume reduction (15)(16)(17)] and dysregultated neurochemistry [e.g., decreased levels of brain-derived neurotrophic factor (18), increased levels of gamma-aminobutric acid (19), increased levels of pro-inflammatory cytokines (20)], these pain-induced changes in resource utilization may (in part) explain (pain-related) cognitive impairment in chronic pain patients.…”