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Critical components of this network are located in a specialised region of the brain stem called the pre-Botzinger complex (pre-BotC) [ 30].

Del Negro and colleagues showed that progressively elevating neuronal excitability of the pre-BotC of neonatal rats in vitro causes periodic modulation of the inspiratory rhythm, characterised by periodic oscillations, quasiperiodicity and ultimately disorganised aperiodic activity [ 31].

In another experimental study with anesthetised adult cat models, Chen et al found that both focal hypoxia and chemical stimulation of pre-BotC can produce a marked excitation of phasic phrenic nerve discharge, characterized by reduced complexity, estimated with approximate entropy (low ApEn values) [ 32].

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