Neurometabolites in anterior cingulate cortex in chronic fatigue syndrome: a magnetic resonance spectroscopy study at 7 Tesla, by Chi Chen, [Master’s Thesis, Oxford University Sep 2017]
Chronic fatigue syndrome (CFS) is a disorder characterized by prolonged physical and mental fatigue that cannot be explained by another established medical diagnosis. The anterior cingulate cortex (ACC) and putamen are two regions involved in frontal-striatal neural circuitry, which may be related to the pathophysiology of CFS. The aim of this study was to investigate the concentrations of neurometabolites, including glutamate, gamma-aminobutyric acid (GABA) and glutathione, in the ACC and putamen, using magnetic resonance spectroscopy (MRS) at 7 Tesla (7T). In addition, this study also aimed to evaluate resting-state functional connectivity in CFS with functional magnetic resonance imaging (fMRI).
This study involved 12 patients who met the Oxford criteria for CFS and 25 healthy controls. Participants rated themselves on the Chalder Fatigue Questionnaire (CFQ) and the Beck Depression Inventory (BDI). All participants had a single proton (1H) MRS and resting-state fMRI scan with a 7T Siemens MAGNETOM scanner (Siemens, Erlangen, Germany) with a Nova Medical 32 channel receive array head coil. Spectra were measured
from voxels in the ACC (20x20x20 mm), putamen (10x16x20 mm) and occipital cortex (20x20x20 mm). Spectra were analysed with LCModel to obtain absolute concentrations of the neurochemicals. Differences in functional connectivity between CFS and healthy participants were tested using multivariate exploratory linear optimized decomposition into independent components (MELODIC) and dual regression.
Concentrations of putamen glutamate and glutamate+glutamine (Glx) were increased in CFS while that of ACC GABA was decreased. Putamen Glx and ACC glutamine were negatively associated with the severity of self-reported fatigue. There were main effects of CFS diagnosis on glutathione (GSH) and total creatine, indicating decreases of these
neurometabolites in all the regions studied in CFS patients. In addition, the CFS patients demonstrated elevated functional connectivity between the default mode network and right supracalcarine cortex, precuneus cortex and dorsolateral prefrontal cortex.
The increased putamen glutamate, decreased ACC GABA and elevated resting state functional connectivity of the default mode network suggest a hyperactive brain status in CFS. The global decrease of GSH and total creatine also suggest that CFS patients may have an abnormal bioenergetic status with higher oxidative stress.