Muscle fatigue is an exercise-induced reduction in maximal voluntary muscle force. It may arise not only because of peripheral changes at the level of the muscle, but also because the central nervous system fails to drive the motoneurons adequately. Evidence for “central” fatigue and the neural mechanisms underlying it are reviewed, together with its terminology and the methods used to reveal it. Much data suggest that voluntary activation of human motoneurons and muscle fibers is suboptimal and thus maximal voluntary force is commonly less than true maximal force. Hence, maximal voluntary strength can often be below true maximal muscle force. The technique of twitch interpolation has helped to reveal the changes in drive to motoneurons during fatigue. Voluntary activation usually diminishes during maximal voluntary isometric tasks, that is central fatigue develops, and motor unit firing rates decline. Transcranial magnetic stimulation over the motor cortex during fatiguing exercise has revealed focal cha...

Spinal and Supraspinal Factors in Human Muscle Fatigue

Vulnerable periods during the development of the nervous system are sensitive to environmental insults because they are dependent on the temporal and regional emergence of critical developmental processes (i.e., proliferation, migration, differentiation, synaptogenesis, myelination, and apoptosis). Evidence from numerous sources demonstrates that neural development extends from the embryonic period through adolescence. In general, the sequence of events is comparable among species, although the time scales are considerably different. Developmental exposure of animals or humans to numerous agents (e.g., X-ray irradiation, methylazoxymethanol, ethanol, lead, methyl mercury, or chlorpyrifos) demonstrates that interference with one or more of these developmental processes can lead to developmental neurotoxicity. Different behavioral domains (e.g., sensory, motor, and various cognitive functions) are subserved by different brain areas. Although there are important differences between the rodent and human brain, analogous structures can be identified. Moreover, the ontogeny of specific behaviors can be used to draw inferences regarding the maturation of specific brain structures or neural circuits in rodents and primates, including humans. Furthermore, various clinical disorders in humans (e.g., schizophrenia, dyslexia, epilepsy, and autism) may also be the result of interference with normal ontogeny of developmental processes in the nervous system. Of critical concern is the possibility that developmental exposure to neurotoxicants may result in an acceleration of age-related decline in function. This concern is compounded by the fact that developmental neurotoxicity that results in small effects can have a profound societal impact when amortized across the entire population and across the life span of humans.

Critical periods of vulnerability for the developing nervous system: evidence from humans and animal models.

In this review, the authors discuss the properties of chemokines and their receptors and highlight the roles of these chemoattractants in selected clinical disorders.

The Many Roles of Chemokines and Chemokine Receptors in Inflammation

There are many strains of the agents that cause transmissible spongiform encephalopathies (TSEs) or 'prion' diseases. These strains are distinguishable by their disease characteristics in experimentally infected animals, in particular the incubation periods and neuropathology they produce in panels of inbred mouse strains. We have shown that the strain of agent from cattle affected by bovine spongiform encephalopathy (BSE) produces a characteristic pattern of disease in mice that is retained after experimental passage through a variety of intermediate species. This BSE 'signature' has also been identified in transmissions to mice of TSEs of domestic cats and two exotic species of ruminant, providing the first direct evidence for the accidental spread of a TSE between species. Twenty cases of a clinically and pathologically atypical form of Creutzfeldt-Jakob disease (CJD), referred to as 'new variant' CJD (vCJD), have been recognized in unusually young people in the United Kingdom, and a further case has been reported in France. This has raised serious concerns that BSE may have spread to humans, putatively by dietary exposure. Here we report the interim results of transmissions of sporadic CJD and vCJD to mice. Our data provide strong evidence that the same agent strain is involved in both BSE and vCJD.

Transmissions to mice indicate that ‘new variant’ CJD is caused by the BSE agent

Part two of this three-part series commences with anomalous dominance and special talents. Part one appears in a previous issue of theArchives. 1 ANOMALOUS DOMINANCE AND SPECIAL TALENTS According to our hypothesis, slowed growth within certain zones of the left hemisphere is likely to result in enlargement of other cortical regions, in particular, the homologous contralateral area, but also adjacent unfaffected regions. The influences that favor anomalous dominance may thus favor talents associated with superior development of certain regions either in the right hemisphere or in adjacent parts of the left hemisphere. Even with excessive retardation of growth and the resultant migration abnormalities and learning disorders (LD), high talents may exist as a result of compensatory enlargement of other cortical regions. Several types of data are in concordance with these conclusions. Several studies have claimed that the average level of spatial talents is higher in male subiects. 2 Hier

https://jamanetwork.com/journals/jamaneurology/articlepdf/584161/archneur_42_5_008.pdf

Cerebral lateralization. Biological mechanisms, associations, and pathology: II. A hypothesis and a program for research.

We report an experimental study designed to test the following hypothesis derived from clinical observations: There is an elevated frequency in left-handed individuals and in their families of immune disease, migraine, and developmental learning disorders. In two separate investigations the frequency of these conditions was compared in strongly left-handed subjects and in strongly right-handed controls. In each of the investigations we found markedly higher frequencies of immune disease in the left-handers than in the right-handers. The rate of learning disabilities was also much higher in the left-handers than in the right-handers in both investigations. In a second study the frequency of left-handedness was compared in patients with migraine or immune disease and in general population control subjects free of these disorders. There was a higher frequency of left-handedness in patients with migraine and myasthenia gravis than in controls. We present a brief outline of a hypothesis that may account for an increased frequency of immune disease in left-handers and in their families.

https://www.pnas.org/content/pnas/79/16/5097.full.pdf

Left-handedness: association with immune disease, migraine, and developmental learning disorder.

https://www.thelancet.com/pdfs/journals/lancet/PIIS0140673604157942.pdf

Fatigue in neurological disorders

Fatigue and basal ganglia

The postviral fatigue syndrome — an analysis of the findings in 50 cases

OBJECTIVE--To study the dynamic function of hypothalamic 5-hydroxytryptamine receptors in patients with postviral fatigue syndrome. DESIGN--Prospective comparison of patients with postviral fatigue syndrome with two control groups. SETTING--Department of neurology, University of Glasgow, Southern General Hospital; department of psychiatry, St James9s Hospital, Dublin. SUBJECTS--15 patients with postviral fatigue syndrome, 13 age and sex matched healthy subjects, and 13 patients with primary depression. MAIN OUTCOME MEASURES--Serum prolactin concentrations before and one, two, and three hours after administration of buspirone. RESULTS--Because of the effects of sex hormones on prolactin secretion data for men and women were analysed separately. There was no significant difference in baseline prolactin concentrations between patients with postviral fatigue syndrome and healthy subjects or those with primary depression. However, the percentage difference between peak and baseline values was significantly higher in patients with postviral fatigue syndrome than the control groups (one way analysis of variance: women, p = 0.003; men, p = 0.004). CONCLUSIONS--The results suggest upregulation of hypothalamic 5-hydroxytryptamine receptors in patients with postviral fatigue syndrome but not in those with primary depression. The buspirone challenge test may therefore be useful in distinguishing these two conditions. Larger studies are required to explore the potential value of drugs acting on central 5-hydroxytryptamine receptors in the treatment of patients with the postviral fatigue syndrome.

Peter O. Behan

Papers

Left-handedness: association with immune disease, migraine, and developmental learning disorder.

Fatigue in neurological disorders

Fatigue and basal ganglia

The postviral fatigue syndrome — an analysis of the findings in 50 cases

Possible upregulation of hypothalamic 5-hydroxytryptamine receptors in patients with postviral fatigue syndrome.