fMRI of cerebral responses to breathing of mindfulness and slow paced breathing at brainstem and higher brain - Mindfulness (M) in this proposal is focused on attention to breathing given the limited scope of R21. Breath plays an important role in mindfulness. First, since M uses the breath as an anchor, the brain rhythm of the awareness of breath is expected to be correlated with the rhythm of breathing. Secondly, as M can change the breathing pattern without consciously controlling it, the rhythm of breathing should also be correlated with the rhythm of specific brain regional activities significantly affected by the breathing. Hence we propose to use functional magnetic resonance imaging (fMRI) to study the brain-body interaction of M by mapping the regional brain responses to breathing at both the brainstem and the higher brain. Brainmapping from the brainstem to the hypothalamus and thalamus with extension to higher brain is used to obtain evidence-based regional results relevant to benefits of clinical interest for M. Since the breathing rate of M can be much slower than that of spontaneous breathing (S), we will compare the brain responses to breathing between M and slow-paced breathing at six breaths per minute (P). Breathing is characterized in this proposal by respiratory gas exchange (RGE) of O2 and CO2. The RGE metric of choice is breath-by-breath O2-CO2 exchange ratio (bER) which takes both O2 and CO2 into account and was shown to be superior to the more common ventilatory parameters of breathing rate and variability in correlation with the rhythm of cerebral hemodynamic fluctuations (CHF). bER-CHF correlation which maps brain responses to the RGE components of breathing is most significant at the frequency range below 0.03Hz which provides new physiological information outside the range (0.05 Hz and above) routinely investigated for low frequency heart rate variability and blood pressure variation. bER-CHF correlation is an especially suitable probe for brainstem functions because RGE reflects not only ventilation but also cardiac output. Cardiorespiratory coupling had been reported in the literature of M and P to contribute to the modulation of respiratory sinus arrhythmia (RSA), blood pressure, awareness and sleep-wake cycle, all critical health-related functions regulated at the brainstem respiratory and cardiac control networks with connection to the ascending arousal network. Despite sharing similar characteristics of slower breathing, M and P have opposite RGE outcomes as breathing for M tends to be shallow while breathing for P can be deep. The RGE characteristics of M share certain features with non-REM sleep such as lower systemic O2 level attributed to the health benefits of relaxation even though M with full awareness is not sleep. Our pilot brainmapping findings demonstrated the potential to clarify the neuromechanisms of M vs. P by showing regions with significant bER-CHF correlation applicable to M but not to P together with significant regions common to M and P. M and P modulate also the variation in heart rate (HR). fMRI mapping of bER-CHF correlation and HR-CHF correlation will be obtained during M, P and S in experienced mindfulness practitioners and naïve volunteers.