Seiki Tajima

Central nervous system fatigue alters autonomic nerve activity.

AIMS Fatigue is a common symptom in modern society. In order to clarify the mechanisms underlying fatigue, we examined the association between central nervous system fatigue and autonomic nerve activity. MAIN METHODS The study group consisted of 20 healthy subjects. They performed the 2-back test for 30 min to induce fatigue. Just before and after the fatigue-inducing session, they completed the advanced trail making test (ATMT) for 30 min as a fatigue-evaluating task session. In order to measure autonomic nerve activity, electrocardiograms were monitored continuously throughout the experiment. KEY FINDINGS After the fatigue-inducing task session, impaired task performance was demonstrated based on the total trial number and error counts of the ATMT. During the task session, although task performance as measured using the accuracy and the mean reaction time of the 2-back test was almost unchanged, electrocardiographic R-R wave interval analyses showed a decreased high-frequency component power and an increasing trend in the low-frequency component power/high-frequency component power ratio. SIGNIFICANCE Decreased vagal nerve activity and increased sympathetic nerve activity are associated with central nervous system fatigue.

Medial Orbitofrontal Cortex Is Associated with Fatigue Sensation

Fatigue is an indispensable bioalarm to avoid exhaustive state caused by overwork or stresses. It is necessary to elucidate the neural mechanism of fatigue sensation for managing fatigue properly. We performed H2 15O positron emission tomography scans to indicate neural activations while subjects were performing 35-min fatigue-inducing task trials twice. During the positron emission tomography experiment, subjects performed advanced trail-making tests, touching the target circles in sequence located on the display of a touch-panel screen. In order to identify the brain regions associated with fatigue sensation, correlation analysis was performed using statistical parametric mapping method. The brain region exhibiting a positive correlation in activity with subjective sensation of fatigue, measured immediately after each positron emission tomography scan, was located in medial orbitofrontal cortex (Brodmanns area 10/11). Hence, the medial orbitofrontal cortex is a brain region associated with mental fatigue sensation. Our findings provide a new perspective on the neural basis of fatigue.

Personality traits associated with intrinsic academic motivation in medical students

Objectives  Motivation is one of the most important psychological concepts in education and is related to academic outcomes in medical students. In this study, the relationships between personality traits and intrinsic academic motivation were examined in medical students.

Premorbid personality in chronic fatigue syndrome as determined by the Temperament and Character Inventory

BACKGROUND Using the Temperament and Character Inventory (TCI), we examined personality characteristics in patients with chronic fatigue syndrome (CFS) compared with healthy control subjects, and CFS patients with and without psychiatric diseases. There have been no previous reports assessing personality in CFS patients using the TCI. METHODS A total of 211 CFS patients and 90 control subjects completed the TCI and the Chalder Fatigue Scale questionnaires. RESULTS Compared with control subjects, CFS patients demonstrated significantly lower premorbid Novelty Seeking, and higher Harm Avoidance and persistence. The fatigue score for CFS patients with psychiatric diseases was higher than that for CFS patients without psychiatric diseases. Patients with CFS with psychiatric diseases showed lower premorbid Self-Directedness when compared with CFS patients without psychiatric diseases. The fatigue score was negatively correlated with premorbid Self-Directedness and Cooperativeness, and positively correlated with Harm Avoidance among CFS patients. CONCLUSION This study supported the stereotyped image of CFS patients as perfectionists, which is similar to the Persistence score, and neurotics, which is similar to the Harm Avoidance score. Patients displaying greater neuroticisms and poorer social and communication skills, similar to the Self-Directedness and Cooperativeness scores, tend to have intercurrent psychiatry diseases and show more severe symptoms of CFS.

Index markers of chronic fatigue syndrome with dysfunction of TCA and urea cycles

Chronic fatigue syndrome (CFS) is a persistent and unexplained pathological state characterized by exertional and severely debilitating fatigue, with/without infectious or neuropsychiatric symptoms, lasting at least 6 consecutive months. Its pathogenesis remains incompletely understood. Here, we performed comprehensive metabolomic analyses of 133 plasma samples obtained from CFS patients and healthy controls to establish an objective diagnosis of CFS. CFS patients exhibited significant differences in intermediate metabolite concentrations in the tricarboxylic acid (TCA) and urea cycles. The combination of ornithine/citrulline and pyruvate/isocitrate ratios discriminated CFS patients from healthy controls, yielding area under the receiver operating characteristic curve values of 0.801 (95% confidential interval [CI]: 0.711–0.890, P < 0.0001) and 0.750 (95% CI: 0.584–0.916, P = 0.0069) for training (n = 93) and validation (n = 40) datasets, respectively. These findings provide compelling evidence that a clinical diagnostic tool could be developed for CFS based on the ratios of metabolites in plasma.

Reduction of [11C](+)3-MPB Binding in Brain of Chronic Fatigue Syndrome with Serum Autoantibody against Muscarinic Cholinergic Receptor

Background Numerous associations between brain-reactive antibodies and neurological or psychiatric symptoms have been proposed. Serum autoantibody against the muscarinic cholinergic receptor (mAChR) was increased in some patients with chronic fatigue syndrome (CFS) or psychiatric disease. We examined whether serum autoantibody against mAChR affected the central cholinergic system by measuring brain mAChR binding and acetylcholinesterase activity using positron emission tomography (PET) in CFS patients with positive [CFS(+)] and negative [CFS(−)] autoantibodies. Methodology Five CFS(+) and six CFS(−) patients, as well as 11 normal control subjects underwent a series of PET measurements with N-[11C]methyl-3-piperidyl benzilate [11C](+)3-MPB for the mAChR binding and N-[11C]methyl-4-piperidyl acetate [11C]MP4A for acetylcholinesterase activity. Cognitive function of all subjects was assessed by neuropsychological tests. Although the brain [11C](+)3-MPB binding in CFS(−) patients did not differ from normal controls, CFS(+) patients showed significantly lower [11C](+)3-MPB binding than CFS(−) patients and normal controls. In contrast, the [11C]MP4A index showed no significant differences among these three groups. Neuropsychological measures were similar among groups. Conclusion The present results demonstrate that serum autoantibody against the mAChR can affect the brain mAChR without altering acetylcholinesterase activity and cognitive functions in CFS patients.

A two-year follow-up study of chronic fatigue syndrome comorbid with psychiatric disorders.

Aims:  Chronic fatigue syndrome patients often have comorbid psychiatric disorders such as major depressive disorders and anxiety disorders. However, the outcomes of chronic fatigue syndrome and the comorbid psychiatric disorders and the interactions between them are unknown. Therefore, a two‐year prospective follow‐up study was carried out on chronic fatigue syndrome patients with comorbid psychiatric disorders.

Visible and near-infrared spectral changes in the thumb of patients with chronic fatigue syndrome

BACKGROUND Chronic fatigue syndrome (CFS) patients show a persistent fatigue condition with muscle pain and impairment of concentration, memory, and sleep. Presently, the physiological basis of CFS remains unclear. In this study, spectroscopic differences in the thumb were compared between 103 CFS patients and 122 healthy controls to examine possible changes of levels of oxygenated or deoxygenated hemoglobin. METHODS Visible and near-infrared (Vis-NIR) spectroscopy was used to examine possible changes in the region of 600-1100 nm. RESULTS Vis-NIR spectra showed sharp peaks at 694, 970 and 1060 nm and broad peaks in the regions of 740-760 and 830-850 nm. As these peaks are possibly related to oxyhemoglobin, cytochrome c oxidase and water, levels of these factors were compared between the two groups. Statistical analysis of the absorbance of Vis-NIR spectra showed a significant decrease in water content, a significant increase in oxyhemoglobin content, and a significant increase in the oxidation of heme a+a(3) and copper in cytochrome c oxidase in CFS patients. CONCLUSIONS These changes imply accelerated blood flow and energy metabolism in the thumbs of CFS patients.

Autonomic Function is Associated With Health-Related Quality of Life in Patients With End-Stage Renal Disease: A Case-Control Study

OBJECTIVE In the present study, we assessed the associations among fatigue, quality of life (QOL), clinical parameters, and body mass index (BMI) with autonomic function in end-stage renal disease (ESRD) patients undergoing hemodialysis as well as fatigue-free healthy subjects. DESIGN AND METHODS This was a case-control study. This study compared autonomic function in ESRD patients (n = 192) to that of healthy subjects (n = 282) and evaluated its association with fatigue, QOL, and clinical parameters such as glucose, albumin, cholesterol, and BMI. Fatigue was evaluated by a recently established fatigue questionnaire and performance status, and QOL was evaluated with the kidney disease QOL questionnaire. With regards to autonomic function, spontaneous beat-to-beat variations were measured, according to time- (standard deviation of all normal a-wave intervals [CVa-a%]) and frequency domains (low frequency [LF] power, high frequency [HF] power, and LF/HF ratio) with acceleration plethysmography. RESULTS CVa-a%, LF power, HF power, and LF/HF ratio were significantly lower in ESRD patients than healthy subjects. There were significant inverse correlations between these factors and age in healthy subjects, but not in ESRD patients. Although the fatigue score was not associated with any autonomic parameters, ESRD patients with impaired performance status exhibited a significantly lower LF/HF ratio. Moreover, in ESRD patients, the LF/HF ratio was significantly and positively associated with several components of QOL, including physical functioning and role emotional, independent of other clinical parameters and BMI. CONCLUSIONS Impaired autonomic function is significantly associated with fatigue and impaired QOL in dialysis patients.

Autonomic Dysfunction in Chronic Fatigue Syndrome

Symptoms of autonomic dysfunction are one of the characteristic features of the clinical condition known as chronic fatigue syndrome (CFS). In this study we examined the autonomic nerve functions in 1,099 patients with CFS and in 361 normal healthy controls. The autonomic nerve functions were studied in terms of heart rate variability and spectral analysis, and by using the maximal Lyapunov exponent (MLE) and chaotic analysis. The heart rate variability analysis revealed that both the logarithmic low-frequency power (Log LF) and logarithmic high-frequency power (Log HF) were reduced significantly with age in healthy subjects (p < 0.005). When we compared these parameters between the CFS patients and healthy controls according to age groups, there was no significant difference in Log LF between CFS and control except in the case of the 40s age group. However, Log HF decreased significantly in moderate and severe fatigue CFS groups in all age groups. All of the severe fatigue CFS age groups had a significant increase in the ratio of Log LF/HF as compared with that of the healthy controls. When we studied the change in these power values during sleep as compared with that during awake time, the HF power rose 3.03-fold in the controls and 1.86-fold in the CFS group during sleep as compared with that during the awake time; and this difference in fold increase during sleep between the CFS and control groups was significant (p < 0.05). Furthermore, the MLE for both the moderate and severe fatigue CFS groups was decreased significantly as compared with that of the healthy control group (p < 0.01). It is well known that autonomic nervous function differs greatly in individuals, but our present large research study indicates that there is no doubt that parasympathetic nervous dysfunction is involved in the pathophysiology of CFS patients with severe fatigue. We incorporated the evaluation of autonomic function into the Japanese CFS diagnostic criteria in 2012, because this evaluation might be a useful objective diagnostic tool for CFS.