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              <p>Background: Breathing in humans is dually controlled for metabolic (brainstem commands) and behavioral purposes (suprapontine commands) with reciprocal modulation through spinal integration. Whereas the ventilatory response to chemical stimuli arises from the brainstem, the compensation of mechanical loads in awake humans is thought to involve suprapontine mechanisms. The aim of this study was to test this hypothesis by examining the effects of inspiratory resistive loading on the response of the diaphragm to transcranial magnetic stimulation. Results: Six healthy volunteers breathed room air without load (R0) and then against inspiratory resistances (5 and 20 cmH 2 O/L/s, R5 and R20). Ventilatory variables were recorded. Transcranial magnetic stimulation (TMS) was performed during early inspiration (I) or late expiration (E), giving rise to motor evoked potentials (MEPs) in the diaphragm (Di) and abductor pollicis brevis (APB). Breathing frequency significantly decreased during R20 without any other change. Resistive breathing had no effect on the amplitude of Di MEPs, but shortened their latency (R20:-0.903 ms, p = 0.03) when TMS was superimposed on inspiration. There was no change in APB MEPs. Conclusion: Inspiratory resistive breathing facilitates the diaphragm response to TMS while it does not increase the automatic drive to breathe. We interpret these findings as a neurophysiological substratum of the suprapontine nature of inspiratory load compensation in awake humans. Background Breathing in humans fulfils both metabolic and behavioral functions. The automatic activity of brainstem central pattern generators continuously adapts ventilation to the production of carbon dioxide by the tissues. Suprapontine descending pathways convey voluntary and emotional respiratory commands that are independent of bodily requirements. Spinal respiratory motoneurons integrate</p>
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