Cortico-limbic circuitry and the airways: Insights from functional neuroimaging of respiratory afferents and efferents

Abstract

After nearly two decades of active research, functional neuroimaging has demonstrated utility in the identification of cortical, limbic, and paralimbic (cortico-limbic) brain regions involved in respiratory control and respiratory perception. Before the recent boon of human neuroimaging studies, the location of the principal components of respiratory-related cortico-limbic circuitry had been unknown and their function had been poorly understood. Emerging neuroimaging evidence in both healthy and patient populations suggests that cognitive and emotional/affective processing within cortico-limbic circuitry modulates respiratory control and respiratory perception. This paper will review functional neuroimaging studies of respiration with a focus on whole brain investigations of sensorimotor pathways that have identified respiratory-related neural circuitry known to overlap emotional/affective cortico-limbic circuitry. To aid the interpretation of present and future findings, the complexities and challenges underlying neuroimaging methodologies will also be reviewed as applied to the study of respiration physiology.

Breathing-controlled Electrical Stimulation (BreEStim) for Management of Neuropathic Pain and Spasticity

“…This enhanced clinical outcome and broader clinical applications of BreEStim are attributed to its unique approach. Intervention with electrical stimulation targeted at the short window of voluntary breathing-associated cortical and subcortical activation [40][41][42][43][44][45][46][47][48][49][50][51] could augment its clinical efficacy via intrinsic physiological coupling, e.g., respiratory-motor coupling for spasticity management 16 . In this intervention, voluntary breathing becomes critical, particularly voluntary inspiration.…”

“…During voluntary breathing, humans need to voluntarily suppress autonomic control of breathing through voluntary cortical activation (the "cortical respiratory center") 38,39 . Brain imaging studies [40][41][42][43][44][45][46][47][48][49][50][51] have demonstrated extensive respiratory-related involvement of cortical areas bilaterally, including the primary motor cortex (M1), the premotor cortex, the supplementary motor area, the primary and secondary somatosensory cortices, the insula, the anterior cingulate cortex and amygdala, and the dorsolateral prefrontal cortex. The insula is known to have strong connections to brainstem centers and is involved in pain processing 52 .…”

An Official American Thoracic Society Statement: Update on the Mechanisms, Assessment, and Management of Dyspnea

“…Nonetheless, some important conclusions can be drawn from several studies that have produced similar results using different approaches. A core pattern has emerged: dyspnea activates cortico-limbic structures (134)(135)(136)(137)(138)(139)(140)(141)(142)(143) that also subserve interoceptive awareness of homeostatic threats such as thirst and hunger (144)(145)(146)(147)(148) or pain (134,(137)(138)(139)(140)(149)(150)(151)(152). Recent reviews provide a comprehensive analysis of both the power and limitations of these techniques (141,153).…”

Neurodegenerative Disorders Increase Decline in Respiratory Muscle Strength in Older Adults

“…The diaphragm, the principal human respiratory muscle, receives input from the phrenic motor neuron, originating from three main pathways: (1) the bulbo-spinal pathway, responsible for promoting the rhythmic respiratory pattern; (2) the cortico-bulbar-spinal pathway, which is involved, through its connection with the limbic system, in the modulation of respiration by emotion; and (3) the upper cortical pathways, which regulate respiration according to the synergic activation of other cerebral areas, such as speech or singing, for example. 21,22 Thus, it is possible to assert that changes in one of these pathways may affect the efficacy of the muscle of the diaphragm.…”