The hypotheses to be tested in this project are that the motor system is altered in patients with CFS along with cytokine production and responsiveness. The sequence of neural events intervening between stimulus presentation and motor response will be studied in patients with CFS when relatively rested and again following exercise-induced fatigue. The neuro- physiological measures to be made include sensory event-related potential (that is, auditory brainstem potentials), cognitive event- related potentials in a short-term memory task and pre- movement-related potentials. Also to be measured are excitability changes of motor cortex prior to movement, conductivity velocity of pyramidal tract and sensory- motor cortex responses to muscle afferent activity. Cytokines will be measured in the serum and the cultured supernatants of LPS-stimulated adherent cells and phytohemagglutinin (PHA)-stimulated T cells by ELISA and bioassays. Cytokine mRNA will be measured by MAPPing with polymerase chain reaction (PCR) using specific probes. Cytokine receptors will be analyzed on T cells and macrophages at the mRNA level with PCR and at the protein level by immunoblot using monoclonal antibodies. The results should provide objective measures of fatigue in CFS, localize the alteration of motor responsiveness to particular neural site(s) and to define how motor response changes correlate with cytokine production and cytokine receptor expression.
