Apnea-Induced Cortical BOLD-fMRI and Peripheral Sympathoneural Firing Response Patterns of Awake Healthy Humans

Abstract

End-expiratory breath-holds (BH) and Mueller manoeuvres (MM) elicit large increases in muscle sympathetic nerve activity (MSNA). In 16 healthy humans (9♀, 35±4 years) we used functional magnetic resonance imaging with blood oxygen level-dependent (BOLD) contrast to determine the cortical network associated with such sympathoexcitation. We hypothesized that increases in MSNA evoked by these simulated apneas are accompanied by BOLD contrast changes in the insular cortex, thalamus and limbic cortex. A series of 150 whole-brain images were collected during 3 randomly performed 16-second end-expiratory BHs and MMs (-30 mmHg). The identical protocol was repeated separately with MSNA recorded from the fibular nerve. The time course of the sympathoexcitatory response to both breathing tasks were correlated with whole-brain BOLD signal changes. Brain sites demonstrating both positive (activation) and negative (deactivation) correlations with the MSNA time course were identified. Sympathetic burst incidence increased (p<0.001) from 29±6 (rest) to 49±6 (BH) and 47±6 bursts/100 heartbeats (MM). Increased neural activity (Z-scores) was identified in the right posterior and anterior insular cortices (3.74, 3.64), dorsal anterior cingulate (3.42), fastigial and dentate cerebellar nuclei (3.02, 3.34). Signal intensity decreased in the left posterior insula (3.28) and ventral anterior cingulate (3.01). Apnea both activates and inhibits elements of a cortical network involved in the generation of sympathetic outflow. These findings identify a neuroanatomical substrate to guide future investigations into central mechanisms contributing to disorders characterized by elevated basal MSNA and exaggerated sympathetic responses to simulated apneas such as sleep apnea and heart failure.

Arousal From Sleep and Sympathetic Excitation During Wakefulness

“…36 An external challenge shown to induce long-term transcription factor changes within forebrain and medullary structures involved in blood pressure regulation, and one that is proposed by several groups to act as the principal stimulus to OSA-induced brain stem and cortical neuroplasticity is chronic intermittent apnea with hypoxia and 18,32,37,38 Simulated apnea, itself, elicits concurrent changes in MSNA and in blood flow within cortical autonomic centers engaged in autonomic cardiovascular regulation. 39 However, because Fatouleh et al 19 found no overlap between brain regions of sleep apnea subjects showing structural and functional changes, these authors concluded that asphyxic damage because of repeated episodes of nocturnal apnea is not the main cause of the sympathoexcitation of OSA.…”

“…18,32,37,38 La apnea simulada, por sí misma, provoca cambios concurrentes de la ANSM y del flujo sanguíneo dentro de los centros autónomos corticales involucrados en la regulación cardiovascular autónoma. 39 Sin embargo, como Fatouleh et al 19 no hallaron ninguna superposición entre regiones encefálicas de sujetos con apnea del sueño Figura. Correlaciones entre posibles variables predictivas y descarga simpática diurna.…”

Muscle sympathetic nerve activity‐coupled changes in brain activity during sustained muscle pain

“…In all regions, there is a significant linear relationship between MSNA burst-to-burst signal changes during tonic pain compared with baseline with the overall change in MSNA amplitude. PAG, periaqueductal gray the ACC and dlPFC are both activated during cardiovascular challenges such an inspiratory capacity apnea (Kimmerly, Morris, & Floras, 2013;Macefield, Gandevia, & Henderson, 2006). Furthermore, we have shown that these regions display MSNA-coupled signal changes even at rest.…”

“…A role for these regions in mediating changes in autonomic function has been recognized for some time. For example, the ACC and dlPFC are both activated during cardiovascular challenges such an inspiratory capacity apnea (Kimmerly, Morris, & Floras, ; Macefield, Gandevia, & Henderson, ). Furthermore, we have shown that these regions display MSNA‐coupled signal changes even at rest.…”

Pediatric Functional Magnetic Resonance Imaging: Clinical Applications

“…Depending on patient comfort and tolerance, short-duration breath holds may be used and result in slightly less robust datasets. [55][56][57][58][59][60][61][62] Obtaining quality breath-hold fMRI scans can be difficult in young children as a result of insufficient task compliance as well as age-dependent variation in respiratory physiology, which complicates postprocessing and analysis of the scans. In the future, MRI-compatible inhaled CO 2 delivery devices may prove useful for obtaining CVR analyses in these patients.…”