Beyond the symptom: the biology of fatigue.

A workshop titled "Beyond the Symptom: The Biology of Fatigue" was held virtually September 27-28, 2021. It was jointly organized by the Sleep Research Society and the Neurobiology of Fatigue Working Group of the NIH Blueprint Neuroscience Research Program. For access to the presentations and video recordings, see: https://neuroscienceblueprint.nih.gov/about/event/beyond-symptom-biology-fatigue. The goals of this workshop were to bring together clinicians and scientists who use a variety of research approaches to understand fatigue in multiple conditions and to identify key gaps in our understanding of the biology of fatigue. This workshop summary distills key issues discussed in this workshop and provides a list of promising directions for future research on this topic. We do not attempt to provide a comprehensive review of the state of our understanding of fatigue, nor to provide a comprehensive reprise of the many excellent presentations. Rather, our goal is to highlight key advances and to focus on questions and future approaches to answering them.

The interaction of cortico-spinal pathways and sacral sphincter reflexes in subjects with incomplete spinal cord injury: a pilot study.

AIMS: To reveal the effectiveness of corticospinal drive in facilitating the pudendal reflex in the anal sphincter muscle, as a surrogate marker for the urethral sphincter, in incomplete spinal cord injury (iSCI). METHODS: Three neurologically normal subjects and twenty-six subjects with incomplete, supra-sacral spinal cord injuries and symptoms of a neuropathic bladder were recruited. Incontinence was assessed using the International Consultation on Incontinence Modular Questionnaire (ICIQ). Electromyographic activity of the external anal sphincter was recorded. The pudendo-anal reflex (PAR) was elicited by electrical stimulation of the dorsal penile nerve (DPN). Motor cortical excitation was achieved using transcranial magnetic stimulation (TMS). RESULTS: Preliminary findings in normal and iSCI subjects showed facilitation of the PAR by prior TMS with an optimal interval of 20-40 msec. Of 23 iSCI subjects, 12 showed facilitation to TMS applied 30 msec before DPN stimulation. Eight of the 12, and a further five iSCI subjects, had an anal sphincter MEP in response to TMS alone. There was a weak tendency (r(2) = 0.22, P = 0.03) for those with higher ICIQ values to have larger PAR responses but no significant difference in ICIQ scores between those with (ICIQ = 4.9 ± 4.0 mean ± SD) and those without (ICIQ = 7.2 ± 4.7) cortical facilitation of the PAR. CONCLUSIONS: Cortical TMS was effective in facilitating the PAR in some iSCI subjects. The presence of cortical facilitation of the PAR was not related to the degree of urinary continence.