Tag: brain function

Neurochemical abnormalities in chronic fatigue syndrome: a pilot magnetic resonance spectroscopy study at 7 Tesla

Abstract:

Rationale: Chronic fatigue syndrome (CFS) is a common and burdensome illness with a poorly understood pathophysiology, though many of the characteristic symptoms are likely to be of brain origin. The use of high-field proton magnetic resonance spectroscopy (MRS) enables the detection of a range of brain neurochemicals relevant to aetiological processes that have been linked to CFS, for example, oxidative stress and mitochondrial dysfunction.

Methods: We studied 22 CFS patients and 13 healthy controls who underwent MRS scanning at 7 T with a voxel placed in the anterior cingulate cortex. Neurometabolite concentrations were calculated using the unsuppressed water signal as a reference.

Results: Compared to controls, CFS patients had lowered levels of glutathione, total creatine and myo-inositol in anterior cingulate cortex. However, when using N-acetylaspartate as a reference metabolite, only myo-inositol levels continued to be significantly lower in CFS participants.

Conclusions: The changes in glutathione and creatine are consistent with the presence of oxidative and energetic stress in CFS patients and are potentially remediable by nutritional intervention. A reduction in myo-inositol would be consistent with glial dysfunction. However, the relationship of the neurochemical abnormalities to the causation of CFS remains to be established, and the current findings require prospective replication in a larger sample.

Source: Godlewska BR, Williams S, Emir UE, Chen C, Sharpley AL, Goncalves AJ, Andersson MI, Clarke W, Angus B, Cowen PJ. Neurochemical abnormalities in chronic fatigue syndrome: a pilot magnetic resonance spectroscopy study at 7 Tesla. Psychopharmacology (Berl). 2021 Oct 5. doi: 10.1007/s00213-021-05986-6. Epub ahead of print. PMID: 34609538. https://pubmed.ncbi.nlm.nih.gov/34609538/

Brain function characteristics of chronic fatigue syndrome: A task fMRI study

Abstract:

The mechanism underlying neurological dysfunction in chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is yet to be established. This study investigated the temporal complexity of blood oxygenation level dependent (BOLD) changes in response to the Stroop task in CFS patients. 43 CFS patients (47.4 ± 11.8 yrs) and 26 normal controls (NCs, 43.4 ± 13.9 yrs) were included in this study. Their mental component summary (MCS) and physical component summary (PCS) from the 36-item Short Form Health Survey (SF-36) questionnaire were recorded. Their Stroop colour-word task performance was measured by accuracy and response time (RT). The BOLD changes associated with the Stroop task were evaluated using a 2-level general linear model approach. The temporal complexity of the BOLD responses, a measure of information capacity and thus adaptability to a challenging environment, in each activated region was measured by sample entropy (SampEn).

The CFS patients showed significantly longer RTs than the NCs (P < 0.05) but no significant difference in accuracy. One sample t-tests for the two groups (Family wise error adjusted PFWE < 0.05) showed more BOLD activation regions in the CFS, although a two sample group comparison did not show significant difference. BOLD SampEns in ten regions were significantly lower (FDR-q < 0.05) in CFS patients. BOLD SampEns in 15 regions were significantly associated with PCS (FDR-q < 0.05) and in 9 regions were associated with MCS (FDR-q < 0.05) across all subjects. SampEn of the BOLD signal in the medioventral occipital cortex could explain 40% and 31% of the variance in the SF-36 PCS and MCS scores, and those in the precentral gyrus could explain an additional 16% and 7% across all subjects.

This is the first study to investigate BOLD signal SampEn in response to tasks in CFS. The results suggest the brain responds differently to a cognitive challenge in patients with CFS, with recruitment of wider regions to compensate for lower information capacity.

Source: Shan ZY, Finegan K, Bhuta S, Ireland T, Staines DR, Marshall-Gradisnik SM, Barnden LR. Brain function characteristics of chronic fatigue syndrome: A task fMRI study. Neuroimage Clin. 2018 Apr 25;19:279-286. doi: 10.1016/j.nicl.2018.04.025. eCollection 2018. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6051500/ (Full study)

Neural Consequences of Post-Exertion Malaise in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

Abstract:

Post exertion malaise is one of the most debilitating aspects of Myalgic Encephalomyelitis/ Chronic Fatigue Syndrome, yet the neurobiological consequences are largely unexplored. The objective of the study was to determine the neural consequences of acute exercise using functional brain imaging.

Fifteen female Myalgic Encephalomyelitis/Chronic Fatigue Syndrome patients and 15 healthy female controls completed 30 minutes of submaximal exercise (70% of peak heart rate) on a cycle ergometer. Symptom assessments (e.g. fatigue, pain, mood) and brain imaging data were collected one week prior to and 24 hours following exercise.

Functional brain images were obtained during performance of: 1) a fatiguing cognitive task – the Paced Auditory Serial Addition Task, 2) a non-fatiguing cognitive task – simple number recognition, and 3) a non-fatiguing motor task – finger tapping. Symptom and exercise data were analyzed using independent samples t-tests. Cognitive performance data were analyzed using mixed-model analysis of variance with repeated measures. Brain responses to fatiguing and non-fatiguing tasks were analyzed using linear mixed effects with cluster-wise (101-voxels) alpha of 0.05.

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome patients reported large symptom changes compared to controls (effect size ≥0.8, p<0.05). Patients and controls had similar physiological responses to exercise (p>0.05). However, patients exercised at significantly lower Watts and reported greater exertion and leg muscle pain (p<0.05).

For cognitive performance, a significant Group by Time interaction (p<0.05), demonstrated pre- to post-exercise improvements for controls and worsening for patients. Brain responses to finger tapping did not differ between groups at either time point. During number recognition, controls exhibited greater brain activity (p<0.05) in the posterior cingulate cortex, but only for the pre-exercise scan. For the Paced Serial Auditory Addition Task, there was a significant Group by Time interaction (p<0.05) with patients exhibiting increased brain activity from pre- to post-exercise compared to controls bilaterally for inferior and superior parietal and cingulate cortices.

Changes in brain activity were significantly related to symptoms for patients (p<0.05). Acute exercise exacerbated symptoms, impaired cognitive performance and affected brain function in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome patients.

These converging results, linking symptom exacerbation with brain function, provide objective evidence of the detrimental neurophysiological effects of post-exertion malaise.

Published by Elsevier Inc.

 

Source: Cook DB, Light AR, Light KC, Broderick G, Shields MR, Dougherty RJ, Meyer JD, VanRiper S, Stegner AJ, Ellingson LD, Vernon SD. Neural Consequences of Post-Exertion Malaise in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Brain Behav Immun. 2017 Feb 16. pii: S0889-1591(17)30051-X. doi: 10.1016/j.bbi.2017.02.009. [Epub ahead of print] https://www.ncbi.nlm.nih.gov/pubmed/28216087

 

Impaired associative learning in chronic fatigue syndrome

Abstract:

Patients with chronic fatigue syndrome (CFS) report cognitive difficulties (impaired attention, memory and reasoning). Neuropsychological tests have failed to consistently find cognitive impairments to the degree reported by CFS patients.

We tested patients with CFS and sedentary controls in protocols designed to measure sensory reactivity and acquisition of the classically conditioned eyeblink response. Patients with CFS exhibited normal sensitivity and responsivity to acoustic stimuli.

However, CFS patients displayed impaired acquisition of the eyeblink response using a delayed-type conditioning paradigm. Sensitivity and responsivity to the airpuff stimulus were normal.

In the absence of sensory/motor abnormalities, impaired acquisition of the classically conditioned eyeblink response indicates an associative deficit. These data suggest organic brain dysfunction within a defined neural substrate in CFS patients.

 

Source: Servatius RJ, Tapp WN, Bergen MT, Pollet CA, Drastal SD, Tiersky LA, Desai P, Natelson BH. Impaired associative learning in chronic fatigue syndrome. Neuroreport. 1998 Apr 20;9(6):1153-7. http://www.ncbi.nlm.nih.gov/pubmed/9601685

 

Outcome in the chronic fatigue syndrome

Comment on: Follow up of patients presenting with fatigue to an infectious diseases clinic. [BMJ. 1992]

 

EDITOR,-Michael Sharpe and colleagues’ follow up study of 177 patients with chronic fatigue of uncertain origin raises several important unanswered questions, which require further investigation. Factors such as a belief that their illness followed an infection, intolerance to alcohol, and membership of a support group for patients with myalgic encephalomyelitis were all associated with an adverse prognosis. Could it be that the authors had identified patients belonging to a distinct postinfectious subgroup as many doctors maintain they do? Clearly, if this is the case future studies of this nature will have to include more objective analysis of persisting viral infection (for example, analysis of muscle biopsy specimens with the polymerase chain reaction rather than tests for VP1 antigen); immune function (for example, function of natural killer cells rather than white cell counts); and hypothalamic-pituitary-axis activity (for example, up regulation of serotonin- I receptors and basal cortisol concentrations) to see if there are characteristic abnormalities that distinguish the postinfectious subgroup.

The high incidence of intolerance to alcohol is noted as intriguing, but from personal experience, as well as from seeing many patients with a classic postinfectious fatigue syndrome, I regard this observation as an important diagnostic feature. In these patients even small amounts of alcohol cause a further deterioration in cognitive function, and I suggest that a physiological explanation may lie in the fact that alcohol increases the concentration of the neurotransmitter y-aminobutyric acid, which in turn reduces the availability of calcium ions and hence depresses brain function still further.

You can read the rest of this comment here: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1883001/pdf/bmj00086-0047c.pdf

 

Source: Shepherd C. Outcome in the chronic fatigue syndrome. BMJ. 1992 Aug 8;305(6849):365. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1883001/