putamen – American ME and CFS Society

Abstract:

Background: 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).

Methods: 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 (20 × 20 × 20 mm), putamen (10 × 16 × 20 mm) and occipital cortex (20 × 20 × 20 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.

Results: 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.

Conclusions: 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.

Source: Chi Chen. Neurometabolites in anterior cingulate cortex in chronic fatigue syndrome: A magnetic resonance spectroscopy study at 7 Tesla. Oxford University Research Archive. September 22, 2017. (Open access article) https://ora.ox.ac.uk/objects/uuid:60ff242e-2ccd-4f23-ac7d-16553d864e8b

Abstract:

Motivational signals influence a wide variety of cognitive processes and components of behavioral performance. Cognitive dysfunction in patients with childhood chronic fatigue syndrome (CCFS) may be closely associated with a low motivation to learn induced by impaired neural reward processing. However, the extent to which reward processing is impaired in CCFS patients is unclear.

The aim of the present functional magnetic resonance imaging (fMRI) study was to determine whether brain activity in regions related to reward sensitivity is impaired in CCFS patients. fMRI data were collected from 13 CCFS patients (mean age, 13.6 ± 1.0 years) and 13 healthy children and adolescents (HCA) (mean age, 13.7 ± 1.3 years) performing a monetary reward task. Neural activity in high- and low-monetary-reward conditions was compared between CCFS and HCA groups. Severity of fatigue and the reward obtained from learning in daily life were evaluated by questionnaires.

Activity of the putamen was lower in the CCFS group than in the HCA group in the low-reward condition, but not in the high-reward condition. Activity of the putamen in the low-reward condition in CCFS patients was negatively and positively correlated with severity of fatigue and the reward from learning in daily life, respectively.

We previously revealed that motivation to learn was correlated with striatal activity, particularly the neural activity in the putamen. This suggests that in CCFS patients low putamen activity, associated with altered dopaminergic function, decreases reward sensitivity and lowers motivation to learn.

Source: Mizuno K, Kawatani J, Tajima K, Sasaki AT, Yoneda T, Komi M, Hirai T, Tomoda A, Joudoi T, Watanabe Y. Low putamen activity associated with poor reward sensitivity in childhood chronic fatigue syndrome. Neuroimage Clin. 2016 Sep 26;12:600-606. eCollection 2016. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5043413/ (Full article)