title: 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.
authors.affiliation: Clinical Cardiovascular Physiology Laboratory, University Health Network and Mount Sinai Hospital Division of Cardiology, Department of Medicine, University of Toronto, Toronto, Ontario, Canada ; School of Health and Human Performance, Faculty of Health Professions, Dalhousie University, Halifax, Nova Scotia, Canada.
authors.forename: Derek S
authors.initials: DS
authors.lastname: Kimmerly
authors.affiliation: Clinical Cardiovascular Physiology Laboratory, University Health Network and Mount Sinai Hospital Division of Cardiology, Department of Medicine, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Beverley L
authors.initials: BL
authors.lastname: Morris
authors.affiliation: Clinical Cardiovascular Physiology Laboratory, University Health Network and Mount Sinai Hospital Division of Cardiology, Department of Medicine, University of Toronto, Toronto, Ontario, Canada.
authors.forename: John S
authors.initials: JS
authors.lastname: Floras
mesh_terms: D000328:Adult; D000368:Aged; D001049:Apnea / Q000503:physiopathology*; D002540:Cerebral Cortex / Q000503:physiopathology*; D005260:Female; D059907:Functional Neuroimaging; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009474:Neurons / Q000502:physiology*; D013564:Sympathetic Nervous System / Q000503:physiopathology*; D014851:Wakefulness / Q000502:physiology; D055815:Young Adult