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Download !!LINK!! Sendr Deep Breath Rar



Proposed time course of peripheral afferent effects during (A) slow, deep breaths, and (B) normal breaths. These hypothetical traces are partly based on records from supportive experiments in anesthetized rats (Ho et al., 2001; Schelegle, 2003). During normal breathing, rapidly-adapting receptors (RARs) are phasically active during inspiration, slowly-adapting receptors (SARs) remain mostly inactive, and baroreceptors are weakly activated during exhalation. During repetitive deep breathing, RARs are activated during the early component of inhalation and then lungs hyperinflate at sufficient pressures to activate low- and high-threshold SARs, increasing traffic through the vagus nerve. Deep exhalations amplify respiratory arterial pressure waves to strongly activate peripheral baroreceptors. Human carotid baroreceptors are slowly-adapting (Eckberg, 1977). Along with these cardiorespiratory vagal afferents, additional airway afferents probably play a significant role in mediating the sensory element of slow, deep breathing, while sensory and motor systems are highly integrated to control the rate of airflow from the lungs and implement cognitive control of respiratory motor drive (see Introduction). BP, blood pressure.




Download Sendr Deep Breath rar


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Proposed mechanisms of NTS-mediated relaxation. Inset: Slowly-adapting pulmonary receptor (SAR) and rapidly-adapting pulmonary receptor (RAR) afferents project to the brainstem at the level of the medulla and innervate the parasympathetic relay nucleus, i.e., the nucleus of the solitary tract (NTS). That SARs project to a distinct anatomical NTS subregion from RARs and baroreceptors and are associated with a differentiable respiratory phenotype (slow and deep) is consistent with SARs serving a distinct function via a state transition in brainstem autonomic signaling. SARs project primarily to GABAergic inhibitory neurons in the ventrolateral subregion of the NTS (vlNTS) (Berger and Dick, 1987; Kubin et al., 2006), while RARs provide input to the more medial and caudal regions of the NTS (mNTS) (Kubin et al., 2006) to recruit noradrenergic output pathways. Aortic arch and carotid sinus baroreceptor primary afferents mimic RARs in their NTS termination patterns (Dean and Seagard, 1995), but are activated during exhalation instead of inhalation (Figure 1). Glutamatergic projections from the NTS are poised to regulate nucleus ambiguus (NA) cardiac vagal neurons (Neff et al., 1998). The ipsilateral mNTS is the major brain area sending projections to the cardioinhibitory region of the NA (Stuesse and Fish, 1984); though direct projections from the vlNTS have been observed, these are apparently less numerous and have not been shown for sake of clarity. Note that although projections from baroreceptor afferents to the NTS and the NTS to NA appear to cross contralaterally, this is for simplicity of illustration; the majority of these projections are ipsilateral. NTS projections may also feed in to the pre-Bötzinger complex (pre-BötC), potentially inactivating Cdh9/Dbx1 pre-BötC neurons that appear to activate the locus coeruleus (LC) via glutamatergic projections (Yackle et al., 2017; Vann et al., 2018), and thereby promoting calming. Outset: NTS projections to the central nucleus of the amygdala (CeA), paraventricular nucleus of the hypothalamus (PVN), and LC may link cardiorespiratory afferent activation to the effects of slow, deep breathing on stress reduction and attention. Noradrenergic NTS neurons project to downstream limbic areas, sending branching collaterals to the CeA and PVN (Petrov et al., 1993). Several nuclei in the NTS (along with the CeA) also project to the LC, potentially modulating central norepinephrine release (Van Bockstaele et al., 1996, 1999; Berridge and Waterhouse, 2003). NTS projections may serve to integrate autonomic responses with this circuitry and influence downstream targets of the LC (Van Bockstaele et al., 1999). The LC also provides noradrenergic projections to the CeA and PVN (Petrov et al., 1993), supporting the possibility of further signal integration at these higher-order hubs of the central autonomic network. Hoxb1 noradrenergic neurons (some of which originate from the NTS) provide a substantial input to the LC and peri-LC dendritic field (Chen et al., 2018) and are one neuronal subpopulation that could potently modulate LC activity, contributing to NTS-mediated relaxation. Interconnectivity between the two arms of this proposed neural pathway could influence peripheral and central release of neuropeptides through the PVN and widespread noradrenergic modulation of forebrain areas through the LC that together may impact arousal and responsiveness to stressors.


Central drive from the respiratory central pattern generator (CPG) exerts an important influence on the heart and thus RSA (Eckberg, 2003), and recent evidence suggests that the core respiratory CPG is embedded within an anatomically distributed pattern-generating network including the NTS (Dhingra et al., 2019). Pulmonary afferent pathways through the NTS are likely one of several important factors contributing to the increase in cardiac oscillation amplitude (visualized by RSA) at the breathing frequency of 0.1 Hz, although their role has been assigned varying degrees of importance ranging from minor (Koh et al., 1998) to obligatory (Taha et al., 1995). The primary factor appears to be the synchronization of respiratory and cardiac oscillations without any delay (unlike during normal breathing), and out of phase by 180 with blood pressure, allowing the baroreflex to be ideally activated (Laude et al., 1993; Lehrer and Gevirtz, 2014). The presence of Mayer waves at 0.1 Hz also reflects baroreceptor resonance effects at this same frequency that contribute to the increase in RSA amplitude. Thus, the powerful modulation of RSA observed during slow and deep breathing is a complex and multifaceted phenomenon that remains only partially understood.


Proposed CNS regions mediating the effects of slow breathing on anxiety, attention, and memory. The locus coeruleus (LC), central nucleus of the amygdala (CeA), and hippocampus (HC) all experience fluctuations in neuronal firing entrained to the respiratory cycle (Zhang et al., 1986a; Chen et al., 1991; Guyenet et al., 1993; Oyamada et al., 1998; Zelano et al., 2016). Despite impacting a broad array of functions, these regions are known to specialize in the regulation of anxiety state (CeA), attention and arousal (LC), and memory (HC), and together project to nearly the entire forebrain. In the forebrain, local processes converge into global respiratory rhythmic slow waves that may serve as the substratum for altered states of consciousness, including those subjectively experienced during meditation techniques involving slow, deep breathing. Interactions between LC, CeA, and HC pathways are proposed to complexly define cognitive and behavioral state. NTS stimulation may also activate the paraventricular nucleus of the hypothalamus (PVN, not shown) through the CeA to regulate the release of cortisol (Ressler, 2010), although this may be an indirect effect (no significant change in hypothalamic activity was observed with stimulation of Hoxb1 noradrenergic neurons, Chen et al., 2018). Dashed lines indicate hypothetical connections. NTS, nucleus of the solitary tract; OB, olfactory bulb; pre-BötC, pre-Bötzinger complex.


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