Cycle-by-cycle respiration waveforms are coupled with the shape of neural oscillations

Beyond sustaining life, breathing is a vital physiological rhythm that shapes cognition, perception, emotional regulation, and mental health. Breathing has a direct effect on neuronal excitability and is coupled to neural oscillations across a variety of brain regions. Notably, both respiration and neural oscillations are asymmetric and not perfectly rhythmic: for example, every breath has a different shape and duration, and is interspersed with variable pauses. Here, we examined the coupling between breathing and the brain by quantifying the nonsinusoidal features of each breath and comparing it to the shape of each corresponding neural oscillation cycle. By leveraging invasive human brain recordings from 16 participants (8 female, 8 male), we found respiration-neural waveform coupling on a breath-by-breath, cycle-by-cycle basis across limbic and cortical forebrain regions. For decades, the dominant perspective on cognition and mental health have focused on the brain, but recent work is highlighting the importance of brain-body interactions. Our results show that the coupling between breathing and neural activity is much richer than previously appreciated, and our approach opens new avenues for studying these peripheral-to-central nervous system interactions in a more robust, temporally precise manner.Significance Statement Breathing shapes brain activity, but prior work has characterized this coupling by aggregating across many breath cycles, leaving the fine-grained shape of individual breaths unexamined. Here, we show that the precise waveform shape of each breath is coupled to the shape of corresponding neural oscillation cycles in the human forebrain, on a breath-by-breath basis. Using invasive brain recordings from 16 epilepsy patients, we demonstrate that temporal and amplitude features of individual breaths are linked to the morphology of neural oscillations in limbic and cortical regions. This cycle-by-cycle respiratory-neural coupling reveals a richer and more temporally precise relationship between breathing and brain activity than previously appreciated.