The Exercising Brain: An Overlooked Factor Limiting the Tolerance to Physical Exertion in Major Cardiorespiratory Diseases?

Abstract

“Exercise starts and ends in the brain”: this was the title of a review article authored by Dr. Bengt Kayser back in 2003. In this piece of work, the author highlights that pioneer studies have primarily focused on the cardiorespiratory-muscle axis to set the human limits to whole-body exercise tolerance. In some circumstances, however, exercise cessation may not be solely attributable to these players: the central nervous system is thought to hold a relevant role as the ultimate site of exercise termination. In fact, there has been a growing interest relative to the “brain” response to exercise in chronic cardiorespiratory diseases, and its potential implication in limiting the tolerance to physical exertion in patients. To reach these overarching goals, non-invasive techniques, such as near-infrared spectroscopy and transcranial magnetic stimulation, have been successfully applied to get insights into the underlying mechanisms of exercise limitation in clinical populations. This review provides an up-to-date outline of the rationale for the “brain” as the organ limiting the tolerance to physical exertion in patients with cardiorespiratory diseases. We first outline some key methodological aspects of neuromuscular function and cerebral hemodynamics assessment in response to different exercise paradigms. We then review the most prominent studies, which explored the influence of major cardiorespiratory diseases on these outcomes. After a balanced summary of existing evidence, we finalize by detailing the rationale for investigating the “brain” contribution to exercise limitation in hitherto unexplored cardiorespiratory diseases, an endeavor that might lead to innovative lines of applied physiological research.

Beyond the Lungs: O2 Supplementation Improves Cerebral Oxygenation and Fatigue during Exercise in Interstitial Lung Disease

“…Comprehensive assessment of cerebral blood flow (e.g., using transcranial Doppler) and the influence of arterial blood gases on brain perfusion would provide additional insights into cerebral hemodynamics and the effects O 2 on these variables during exercise in f -ILD. Also, it remains unknown whether reversing cerebral hypoxia relates to less central fatigue during exercise in f -ILD, which may be explored from changes in cortical voluntary activation by transcranial magnetic stimulation (5).…”

“…The inhibition of the central drive is mostly observed in case of severe hypoxemia (3) and may translate into exacerbated perception of effort/fatigue on exertion (4). It is thus conceivable that impaired cerebral oxygenation might contribute to poor exercise tolerance in chronic respiratory disorders characterized by compromised CaO 2 (5).…”

The Acute Effects of a Single Dose of Molecular Hydrogen Supplements on Responses to Ergogenic Adjustments during High-Intensity Intermittent Exercise in Humans

“…It is possible that the significant increase in PCO 2 at rest is associated with increased cerebral blood flow (CBF), with hypercapnia resulting in dilatation of the cerebral vasculature as PCO 2 , independently and in conjunction with pH, regulates the CBF [ 14 , 15 ]. Regarding the relationship between CBF and exercise performance, it has been documented that a reduced CBF results in a reduced motor drive to working muscles, consequently reducing the tolerance to whole-body exercise and possibly performance [ 16 , 17 ]. The CO 2 -induced CBF might thus have contributed to the change in the 1st PP performance.…”

“…HCP increases HCO 3 − and thus might delay fatigue by increasing the extracellular buffer capacity, which might improve exercise performance [ 11 , 12 , 13 ]. Additionally, as slight increases in PCO 2 might be associated with increased cerebral blood flow (CBF) in humans [ 14 , 15 ], and diminished CBF during exercise or physical activity results in a reduced motor drive to working muscles, consequently negatively affecting the tolerance to whole-body exercise and possibly performance [ 16 , 17 ]. Thus, the increased levels of PCO 2 as result of HCP ingestion might further influence anaerobic exercise performance.…”

Quantifying leg muscle deoxygenation during incremental cycling in hypoxemic patients with fibrotic interstitial lung disease

“…In this context, near‐infrared spectroscopy (NIRS) is a noninvasive optical method particularly suitable to investigate tissue oxygenation during exercise (Marillier et al, 2022). The method allows transcutaneous monitoring of skeletal muscle deoxygenation (deoxyhaemoglobin [HHb]), an index of fractional O 2 extraction (Ferrari et al, 2004; Ferreira et al, 2005a).…”