Disrupted functional brain network organization in patients with obstructive sleep apnea

Abstract

IntroductionObstructive sleep apnea (OSA) subjects show impaired autonomic, affective, executive, sensorimotor, and cognitive functions. Brain injury in OSA subjects appears in multiple sites regulating these functions, but the integrity of functional networks within the regulatory sites remains unclear. Our aim was to examine the functional interactions and the complex network organization of these interactions across the whole brain in OSA, using regional functional connectivity (FC) and brain network topological properties.MethodsWe collected resting‐state functional magnetic resonance imaging (MRI) data, using a 3.0‐Tesla MRI scanner, from 69 newly diagnosed, treatment‐naïve, moderate‐to‐severe OSA (age, 48.3 ± 9.2 years; body mass index, 31 ± 6.2 kg/m2; apnea–hypopnea index (AHI), 35.6 ± 23.3 events/h) and 82 control subjects (47.6 ± 9.1 years; body mass index, 25.1 ± 3.5 kg/m2). Data were analyzed to examine FC in OSA over controls as interregional correlations and brain network topological properties.ResultsObstructive sleep apnea subjects showed significantly altered FC in the cerebellar, frontal, parietal, temporal, occipital, limbic, and basal ganglia regions (FDR, P < 0.05). Entire functional brain networks in OSA subjects showed significantly less efficient integration, and their regional topological properties of functional integration and specialization characteristics also showed declined trends in areas showing altered FC, an outcome which would interfere with brain network organization (P < 0.05; 10,000 permutations). Brain sites with abnormal topological properties in OSA showed significant relationships with AHI scores.ConclusionsOur findings suggest that the dysfunction extends to resting conditions, and the altered FC and impaired network organization may underlie the impaired responses in autonomic, cognitive, and sensorimotor functions. The outcomes likely result from the prominent structural changes in both axons and nuclear structures, which occur in the condition.

Neurodevelopmental Outcomes at Two Years of Age for Premature Infants Diagnosed With Neonatal Obstructive Sleep Apnea

“…This impairment in network organization may result in altered responses in autonomic, cognitive, and sensorimotor functions. 31 Our results did not show any association between AHI and composite scores. Despite the significantly elevated AHI of our study sample, the cognitive scores were within one standard deviation of published norms.…”

Disrupted small-world brain functional network topology in male patients with severe obstructive sleep apnea revealed by resting-state fMRI

“…Previous brain Rs-MRI studies in OSA patients have revealed alterations in cerebellar, frontal, parietal, temporal, thalamic, middle and dorsal prefrontal cortex, left precentral gyrus, and posterior cingulate cortex regions 11–13,16. OSA patients have abnormal Rs-FC in various brain regions that are related to affective, autonomic, sensorimotor, executive, and cognitive regulatory functions 11.…”

“…OSA patients have abnormal Rs-FC in various brain regions that are related to affective, autonomic, sensorimotor, executive, and cognitive regulatory functions 11. However, previous studies were limited to individual brain regions, functionally defined subnetworks, local FC, or independent component analysis,1,13 which cannot directly demonstrate important topological changes in whole-brain functional networks in OSA patients.…”

Arousal From Sleep and Sympathetic Excitation During Wakefulness

“…[11][12][13][14][15][16] This finding has been attributed to an elevation in the set point for efferent sympathetic outflow resulting from progressive carotid body hypersensitivity and altered structure and function of catecholaminergic neurons in brain stem and cortical regions involved in autonomic cardiovascular regulation. 10,[17][18][19][29][30][31][32] Johnson et al 33 have recently reviewed experimental literature demonstrating induction, by transient challenges, of long-lasting changes in synaptic function within a widely distributed network of brain regions engaged in the longterm regulation of blood pressure and the amplification of initial hemodynamic responses by subsequent rechallenge. These data indicate that short-term external stimuli can induce afferent neural and circulating hormonal changes that in turn facilitate molecular neuroplasticity in subcortical and preganglionic components of the sympathetic nervous system, resulting in an elevated prevailing set point for efferent sympathetic nerve firing and consequent norepinephrine release.…”

“…[11][12][13][14][15][16] Este hallazgo se ha atribuido a una elevación del punto de regulación del flujo simpá-tico eferente, que resulta de la hipersensibilidad progresiva del cuerpo carotídeo, y de la alteración de la estructura y función de las neuronas catecolaminérgicas del tronco cerebral y las regiones corticales involucradas en la regulación cardiovascular autónoma. 10,[17][18][19][29][30][31][32] Recientemente, Johnson et al revisaron la bibliografía experimental que demostraba inducción, mediante desafíos transitorios, de cambios duraderos de la función sináptica dentro de una red ampliamente distribuida de regiones encefálicas involucradas en la regulación a largo plazo de la presión arterial y la amplificación de las respuestas hemodinámicas iniciales por re-desafío ulterior. Estos datos indican que los estímulos externos a corto plazo pueden inducir cambios neurales aferentes y hormonales circulantes que, a su vez, facilitan la neuroplasticidad molecular de componentes subcorticales y preganglionares del sistema nervioso simpático, lo que determina un punto de regulación elevado prevalente para la descarga nerviosa simpática eferente y la consiguiente liberación de noradrenalina.…”