Integrative systems 593
Is brain damage really involved in the pathogenesis of obstructive sleep apnea? Jie Lia, Ming-Xian Lib, Sheng-Nan Liub, Jing-Hua Wangb, Min Huangc, Min Wangb and Shao Wangc Obstructive sleep apnea (OSA) syndrome is a surprisingly complex and highly individualized disease, with different factors contributing toward the disease process. Many factors can induce OSA disease, such as hypertrophy uvula, adenoidectomy, tonsil caused by mechanical obstruction of the airway, airway obstruction on obesity cause of decubitus, etc.; in addition, abnormal structure and function of the central nervous system (CNS) is also one of the important factors. This paper examines the relationship of the CNS with the onset of OSA. Evidence has shown that dysfunction of the CNS may be related to the occurrence of OSA. Although modification of the behaviors of the motor neurons may offer a potentially interesting means of controlling the airway, human afferent and motor pathways that regulate eupnea are still poorly understood. Combining some clinical phenomena of patients with cerebral hemorrhage or brain trauma at the temporal lobe, it seems that no close relation with OSA has been observed in clinical work and animal experiments; however, CNS damage at the temporal lobe is involved in the pathogenesis of OSA. This article examines the role of the CNS in the pathogenesis of OSA and its mechanisms. We have summarized previous findings of OSA-related
Obstructive sleep apnea syndrome-related brain changes Apnea often occurs in patients with brain trauma, especially involving the temporal lobe, where the insular cortex (Ic) is located. Temporal lobe injury often induces snoring, apnea, epilepsy, and hypoxia, which are usually considered more severe than the primary brain injury itself because some of these conditions are incurable and fatal [1,2]. The occurrence of snoring and apnea may be because of a direct blow to the temporal lobe or Ic, but it is uncommon after damage to trauma to other parts of the brain. Functional MRI (fMRI) is a useful clinical tool for diagnosing and monitoring central nervous system (CNS) diseases. Previous studies have shown that signal changes in some brain areas, such as the temporal lobe or Ic, are present in obstructive sleep apnea (OSA) patients [1]. In addition, OSA patients show smaller volumes of the cortical gray matter, right hippocampus, and right and left caudate compared with non-OSA controls; moreover, the difference in the volume of the brain parenchymal fraction (a normalized measure of cerebral atrophy) reaches c 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins 0959-4965
brain damage, which were obtained by brain functional MRI, clinical, and animal experiment data to better understand the roles of the CNS in the pathogenesis of OSA. More specifically, this review summarizes how altered activity of the limbic system and its related structures could be associated with the occurrence of OSA. This conclusion may contribute toward our understanding of nosogenesis and the treatment of OSA. NeuroReport c 2014 Wolters Kluwer Health | Lippincott 25:593–595 Williams & Wilkins. NeuroReport 2014, 25:593–595 Keywords: central nervous system, insular cortex, obstructive sleep apnea syndrome, temporal lobe Departments of aGeratology, bPneumology, The First Affiliated Hospital of Jilin University and cDepartment of Physiology, Norman Bethune College of Medicine, Jilin University, Changchun, People’s Republic of China Correspondence to Ming-Xian Li, PhD, Department of Pneumology, The First Affiliated Hospital of Jilin University, 71 Xin Min Street, Changchun 130021, People’s Republic of China Tel: + 86 130 090 04246/ + 86 431 887 82443; fax: + 86 431 885 12588; e-mail: [email protected] Received 7 December 2013 accepted 6 February 2014
statistical significance [3]. This difference remains significant even after controlling for comorbidities (i.e. hypertension, diabetes, smoking, and hypercholesterolemia). Finally, voxel-based morphometry analysis also showed OSA-related decreased volume in the hippocampus and within more lateral temporal areas [3]. Henderson and colleagues [4,5] have observed the CNS response to the Valsalva maneuver in OSA patients. Attenuation in signal changes of the inferior parietal cortex, superior temporal gyrus, posterior Ic, cerebellar cortex, fastigial nucleus, and hippocampus has been observed in these patients compared with healthy controls. Moreover, the anterior cingulate, cerebellar cortex, and posterior insula (Ic) show differential response timing patterns between the controls and OSA patients. Furthermore, another study by Harper et al. [6] used fMRI to analyze the neural responses to a forehead cold pressor challenge in 16 controls and 10 OSA patients without cardiovascular or mood-altering drugs. They found that patients with OSA showed depressed respiration, bradycardia, and enhanced sympathetic outflow. They also observed that the signal increased in the anterior and posterior cingulate and cerebellar and frontal cortex in the brains of OSA patients, when compared with DOI: 10.1097/WNR.0000000000000143
Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
594 NeuroReport 2014, Vol 25 No 8
the controls, whereas signals were markedly decreased in the ventral thalamus, hippocampus, and Ic. An anomalous performance of the above CNS areas shows abnormal reactions in the sensation, motion, and integration function of OSA patients in response to stimulation of apnea or hypoventilation, which can be induced by repeat collapse or relaxation of the respiratory tract muscle and a secondary response of the cardiovascular system. This indicates that neural pathways, which normally mediate instinctive actions, can compensate for hypoxic stress or hypertension or for functions of other brain structures in patients with OSA, as evidenced by lower signals from the medullary, midbrain, lentiform, and cerebellar dentate nuclei in these patients. Physiological responses of cold pressor are modified in OSA, which may result from both reduced and exaggerated responses in multiple brain structures [6]. Different opinions on this respect were recently reported by Ahn et al. [7]; they evaluated patients after ischemic stroke and reported that no specific location was identified for sleep-related breathing disorders and that the size of the stroke lesion appeared unrelated.
Action of the limbic system and central autonomic network in obstructive sleep apnea The mechanisms underlying abnormal signals in the Ic or other cerebral nuclei observed by fMRI in patients with OSA remain to be elucidated. However, the majority of abnormal signals have been observed in the cerebral nuclei of the limbic system or in the central autonomic network (CAN), and research has focused on these sitespecific mechanisms [8]. The sensory and motor nerves and their underlying regulatory systems may be collectively associated with four systems, three sensory systems and one sensory– motor system. The sensory systems include the visual and auditory systems and an independent structure that connects the somatic sensory and motor system [9]. The Ic is a constituent part of the CAN and it also regulates brain functions, controlling activities of the sympathetic nerves, parasympathetic nerves, respiratory motor neurons, and sphincter motor neurons [10,11]. Stimulation of the Ic by L-glutamate in rats has been shown to alter the respiratory rhythm and depth, and to even cause apnea [12]. Our animal experiments showed that the insula cortical electrical stimulation and glutamic acid stimulation signal through rein nuclear conduction, the rat genioglossus electromyography abnormal change, even disappear. When blocking habenula nucleus, animal genioglossus electromyography returned to normal and apnea disappeared. The frontal lobe, Ic, cingulate gyrus, and dopaminergic cells of the mesolimbic system, including the frontal
brain, entorhinal cortex, lateral septal nucleus, amygdala, raphe nucleus, habenula, and accumbens nucleus, also contribute toward conduction of sensory and motor signaling from the periphery to the brain [9]. Animal experiments have shown that stimulation of Ic in rats induced apnea and 5-HT was decreased in the blood and brain stem; however, when blocking the habenula with lidocaine (pharmacological inhibition), the changes were eliminated [11,13,14]. Study of mechanisms related to breathing difficulties should provide insights into how the breathing rhythm works, including occurrence, conduction, and regulation in the peripheral nervous system and CNS. It has been hypothesized that insufficiency of nerve regulation in the sensory and autonomic system may manifest as a dysfunction of the brain in regulating sensory and motor functions, which results in abnormalities in breathing [15].
Obstructive sleep apnea may share similar physiopathological changes with diseases related to the limbic system The forebrain–limbic system has abundant neuronal connections; certain associations among diseases could be related to this system. Accumulating evidence has shown that patients with OSA generally have psychological or psychiatric problems, including excessive sleepiness, irritability, loss of concentration, cognitive deficiency, and depression [16–19]. For instance, clinical symptoms of OSA and depression often occur simultaneously, and treatment of OSA can improve the symptoms of depression as well [20]. In addition, OSA is commonly associated with metabolic syndrome (MS) and obesity [21]. Obesity is known to share some common clinical manifestations, including drowsiness, hypertension, and insulin resistance, which further indicates that these disease states are closely related and links exist between MS and cardiovascular diseases, and they are associated with the limbic system [22–25]. Weaker fMRI signals have also been observed in the gray matter of OSA patients with heart failure. Patients with heart failure often present with high sympathetic and parasympathetic activations. The changes observed in these nerve reactions imply that damage to brain structures induce changes in blood pressure, heart function, and glucose metabolism, all of which are consistent with clinical presentations of OSA. However, it is unclear whether interactions among depression, OSA, and MS increase morbidity and mortality of cardiovascular and cerebrovascular diseases. Such interactions would not be related to heredity; however, they are expected to be associated with insulin resistance. Depression is considered a risk factor of daytime sleepiness, which itself has been correlated with increased BMI, aging, diabetes, smoking, and apneas. Therefore, the limbic system may be associated with OSA, depression, schizophrenia, obesity, and hypertension, and these diseases may share common
Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
Association of OSA with CNS after dysfunction, damage, or trauma Li et al.
neuropathological mechanisms. After the treatment of OSA, for example, the patient’s depression and cognitive function were improved [26,27].
Acknowledgements This article was supported by the National Natural Science Foundation of China, No. V30270502.
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Conflicts of interest
There are no conflicts of interest.
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References
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1
Joo EY, Jeon S, Kim ST, Lee JM, Hong SB. Localized cortical thinning in patients with obstructive sleep apnea syndrome. Sleep 2013; 36: 1153–1162. 2 Santarnecchi E, Sicilia I, Richiardi J, Vatti G, Polizzotto NR, Marino D, et al. Altered cortical and subcortical local coherence in obstructive sleep apnea: a functional magnetic resonance imaging study. J Sleep Res 2013; 22:337–347. 3 Torelli F, Moscufo N, Garreffa G, Placidi F, Romigi A, Zannino S, et al. Cognitive profile and brain morphological changes in obstructive sleep apnea. Neuroimage 2011; 54:787–793. 4 Henderson LA, Woo MA, Macey PM, Macey KE, Frysinger RC, Alger JR, et al. Neural responses during Valsalva maneuvers in obstructive sleep apnea syndrome. J Appl Physiol 2003; 94:1063–1074. 5 Barrera JE. Sleep magnetic resonance imaging: dynamic characteristics of the airway during sleep in obstructive sleep apnea syndrome. Laryngoscope 2011; 121:1327–1335. 6 Harper RM, Macey PM, Henderson LA, Woo MA, Macey KE, Frysinger RC, et al. fMRI responses to cold pressor challenges in control and obstructive sleep apnea subjects. J Appl Physiol 2003; 94:1583–1595. 7 Ahn SH, Kim JH, Kim DU, Choo IS, Lee HJ, Kim HW. Interaction between sleep-disordered breathing and acute ischemic stroke. J Clin Neurol 2013; 9:9–13. 8 Macey KE, Macey PM, Woo MA, Henderson LA, Frysinger RC, Harper PK, et al. Inspiratory loading elicits aberrant fMRI signal changes in obstructive sleep apnea. Respir Physiol Neurobiol 2006; 151:44–60. 9 Oades RD, Halliday GM. Ventral tegmental (A10) system: neurobiology. 1. Anatomy and connectivity. Brain Res 1987; 434:117–165. 10 Cersosimo MG, Benarroch EE. Central control of autonomic function and involvement in neurodegenerative disorders. Handb Clin Neurol 2013; 117:45–57. 11 Pohl A, Anders S, Schulte-Ru¨ther M, Mathiak K, Kircher T. Positive facial affect – an fMRI study on the involvement of insula and amygdala. PLoS One 2013; 8:e69886.
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Cui L, Wang JH, Wang M, Huang M, Wang CY, Xia H, et al. Injection of L-glutamate into the insular cortex produces sleep apnea and serotonin reduction in rats. Sleep Breath 2012; 16:845–853. Wang M, Lin W, Wang J, Huang M, Wang C, Li M, et al. 5-hydroxytryptaminemediated apnea caused by the habenular nucleus. Neural Regen Res 2011; 6:1554–1558. Li M, Wang J, Huang M, Lin W, Wang M, Yu L, et al. Blockage of the habenular nucleus can eliminate dyspnea induced by electrostimulation of the insular cortex. Neural Regen Res 2010; 5:1025–1029. Macefield VG, Gandevia SC, Henderson LA. Neural sites involved in the sustained increase in muscle sympathetic nerve activity induced by inspiratory capacity apnea: a fMRI study. J Appl Physiol 2006; 100:266–273. Twigg GL, Papaioannou I, Jackson M, Ghiassi R, Shaikh Z, Jaye J, et al. Obstructive sleep apnea syndrome is associated with deficits in verbal but not visual memory. Am J Respir Crit Care Med 2010; 182:98–103. Rakel RE. Clinical and societal consequences of obstructive sleep apnea and excessive daytime sleepiness. Postgrad Med 2009; 121:86–95. Halbower AC, Degaonkar M, Barker PB, Earley CJ, Marcus CL, Smith PL, et al. Childhood obstructive sleep apnea associates with neuropsychological deficits and neuronal brain injury. PLoS Med 2006; 3:e301. Dominici M, Gomes Mda M. Obstructive sleep apnea (OSA) and depressive symptoms. Arq Neuropsiquiatr 2009; 67:35–39. Feng J, Chen BY, Chiang AA. Significance of depression in obstructive sleep apnea patients and the relationship between the comorbidity and continuous positive airway pressure treatment. Chin Med J (Engl) 2010; 123:1596–1602. Mariani S, Fiore D, Barbaro G, Basciani S, Saponara M, D’Arcangelo E, et al. Association of epicardial fat thickness with the severity of obstructive sleep apnea in obese patients. Int J Cardiol 2013; 167:2244–2249. Papanas N, Steiropoulos P, Nena E, Tzouvelekis A, Skarlatos A, Konsta M, et al. Predictors of obstructive sleep apnea in males with metabolic syndrome. Vasc Health Risk Manag 2010; 6:281–286. Knight WD, Little JT, Carreno FR, Toney GM, Mifflin SW, Cunningham JT. Chronic intermittent hypoxia increases blood pressure and expression of FosB/DeltaFosB in central autonomic regions. Am J Physiol Regul Integr Comp Physiol 2011; 301:R131–R139. Rubin RR, Gaussoin SA, Peyrot M, DiLillo V, Miller K, Wadden TA, et al. Cardiovascular disease risk factors, depression symptoms and antidepressant medicine use in the Look AHEAD (Action for Health in Diabetes) clinical trial of weight loss in diabetes. Diabetologia 2010; 53:1581–1589. Jean-Louis G, Zizi F, Brown D, Ogedegbe G, Borer J, McFarlane S. Obstructive sleep apnea and cardiovascular disease: evidence and underlying mechanisms. Minerva Pneumol 2009; 48:277–293. Bixler EO, Vgontzas AN, Lin HM, Calhoun SL, Vela-Bueno A, Kales A. Excessive daytime sleepiness in a general population sample: the role of sleep apnea, age, obesity, diabetes, and depression. J Clin Endocrinol Metab 2005; 90:4510–4515. Cross RL, Kumar R, Macey PM, Doering LV, Alger JR, Yan-Go FL, et al. Neural alterations and depressive symptoms in obstructive sleep apnea patients. Sleep 2008; 31:1103–1109.
Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
Is brain damage really involved in the pathogenesis of obstructive sleep apnea? Jie Lia, Ming-Xian Lib, Sheng-Nan Liub, Jing-Hua Wangb, Min Huangc, Min Wangb and Shao Wangc Obstructive sleep apnea (OSA) syndrome is a surprisingly complex and highly individualized disease, with different factors contributing toward the disease process. Many factors can induce OSA disease, such as hypertrophy uvula, adenoidectomy, tonsil caused by mechanical obstruction of the airway, airway obstruction on obesity cause of decubitus, etc.; in addition, abnormal structure and function of the central nervous system (CNS) is also one of the important factors. This paper examines the relationship of the CNS with the onset of OSA. Evidence has shown that dysfunction of the CNS may be related to the occurrence of OSA. Although modification of the behaviors of the motor neurons may offer a potentially interesting means of controlling the airway, human afferent and motor pathways that regulate eupnea are still poorly understood. Combining some clinical phenomena of patients with cerebral hemorrhage or brain trauma at the temporal lobe, it seems that no close relation with OSA has been observed in clinical work and animal experiments; however, CNS damage at the temporal lobe is involved in the pathogenesis of OSA. This article examines the role of the CNS in the pathogenesis of OSA and its mechanisms. We have summarized previous findings of OSA-related
Obstructive sleep apnea syndrome-related brain changes Apnea often occurs in patients with brain trauma, especially involving the temporal lobe, where the insular cortex (Ic) is located. Temporal lobe injury often induces snoring, apnea, epilepsy, and hypoxia, which are usually considered more severe than the primary brain injury itself because some of these conditions are incurable and fatal [1,2]. The occurrence of snoring and apnea may be because of a direct blow to the temporal lobe or Ic, but it is uncommon after damage to trauma to other parts of the brain. Functional MRI (fMRI) is a useful clinical tool for diagnosing and monitoring central nervous system (CNS) diseases. Previous studies have shown that signal changes in some brain areas, such as the temporal lobe or Ic, are present in obstructive sleep apnea (OSA) patients [1]. In addition, OSA patients show smaller volumes of the cortical gray matter, right hippocampus, and right and left caudate compared with non-OSA controls; moreover, the difference in the volume of the brain parenchymal fraction (a normalized measure of cerebral atrophy) reaches c 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins 0959-4965
brain damage, which were obtained by brain functional MRI, clinical, and animal experiment data to better understand the roles of the CNS in the pathogenesis of OSA. More specifically, this review summarizes how altered activity of the limbic system and its related structures could be associated with the occurrence of OSA. This conclusion may contribute toward our understanding of nosogenesis and the treatment of OSA. NeuroReport c 2014 Wolters Kluwer Health | Lippincott 25:593–595 Williams & Wilkins. NeuroReport 2014, 25:593–595 Keywords: central nervous system, insular cortex, obstructive sleep apnea syndrome, temporal lobe Departments of aGeratology, bPneumology, The First Affiliated Hospital of Jilin University and cDepartment of Physiology, Norman Bethune College of Medicine, Jilin University, Changchun, People’s Republic of China Correspondence to Ming-Xian Li, PhD, Department of Pneumology, The First Affiliated Hospital of Jilin University, 71 Xin Min Street, Changchun 130021, People’s Republic of China Tel: + 86 130 090 04246/ + 86 431 887 82443; fax: + 86 431 885 12588; e-mail: [email protected] Received 7 December 2013 accepted 6 February 2014
statistical significance [3]. This difference remains significant even after controlling for comorbidities (i.e. hypertension, diabetes, smoking, and hypercholesterolemia). Finally, voxel-based morphometry analysis also showed OSA-related decreased volume in the hippocampus and within more lateral temporal areas [3]. Henderson and colleagues [4,5] have observed the CNS response to the Valsalva maneuver in OSA patients. Attenuation in signal changes of the inferior parietal cortex, superior temporal gyrus, posterior Ic, cerebellar cortex, fastigial nucleus, and hippocampus has been observed in these patients compared with healthy controls. Moreover, the anterior cingulate, cerebellar cortex, and posterior insula (Ic) show differential response timing patterns between the controls and OSA patients. Furthermore, another study by Harper et al. [6] used fMRI to analyze the neural responses to a forehead cold pressor challenge in 16 controls and 10 OSA patients without cardiovascular or mood-altering drugs. They found that patients with OSA showed depressed respiration, bradycardia, and enhanced sympathetic outflow. They also observed that the signal increased in the anterior and posterior cingulate and cerebellar and frontal cortex in the brains of OSA patients, when compared with DOI: 10.1097/WNR.0000000000000143
Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
594 NeuroReport 2014, Vol 25 No 8
the controls, whereas signals were markedly decreased in the ventral thalamus, hippocampus, and Ic. An anomalous performance of the above CNS areas shows abnormal reactions in the sensation, motion, and integration function of OSA patients in response to stimulation of apnea or hypoventilation, which can be induced by repeat collapse or relaxation of the respiratory tract muscle and a secondary response of the cardiovascular system. This indicates that neural pathways, which normally mediate instinctive actions, can compensate for hypoxic stress or hypertension or for functions of other brain structures in patients with OSA, as evidenced by lower signals from the medullary, midbrain, lentiform, and cerebellar dentate nuclei in these patients. Physiological responses of cold pressor are modified in OSA, which may result from both reduced and exaggerated responses in multiple brain structures [6]. Different opinions on this respect were recently reported by Ahn et al. [7]; they evaluated patients after ischemic stroke and reported that no specific location was identified for sleep-related breathing disorders and that the size of the stroke lesion appeared unrelated.
Action of the limbic system and central autonomic network in obstructive sleep apnea The mechanisms underlying abnormal signals in the Ic or other cerebral nuclei observed by fMRI in patients with OSA remain to be elucidated. However, the majority of abnormal signals have been observed in the cerebral nuclei of the limbic system or in the central autonomic network (CAN), and research has focused on these sitespecific mechanisms [8]. The sensory and motor nerves and their underlying regulatory systems may be collectively associated with four systems, three sensory systems and one sensory– motor system. The sensory systems include the visual and auditory systems and an independent structure that connects the somatic sensory and motor system [9]. The Ic is a constituent part of the CAN and it also regulates brain functions, controlling activities of the sympathetic nerves, parasympathetic nerves, respiratory motor neurons, and sphincter motor neurons [10,11]. Stimulation of the Ic by L-glutamate in rats has been shown to alter the respiratory rhythm and depth, and to even cause apnea [12]. Our animal experiments showed that the insula cortical electrical stimulation and glutamic acid stimulation signal through rein nuclear conduction, the rat genioglossus electromyography abnormal change, even disappear. When blocking habenula nucleus, animal genioglossus electromyography returned to normal and apnea disappeared. The frontal lobe, Ic, cingulate gyrus, and dopaminergic cells of the mesolimbic system, including the frontal
brain, entorhinal cortex, lateral septal nucleus, amygdala, raphe nucleus, habenula, and accumbens nucleus, also contribute toward conduction of sensory and motor signaling from the periphery to the brain [9]. Animal experiments have shown that stimulation of Ic in rats induced apnea and 5-HT was decreased in the blood and brain stem; however, when blocking the habenula with lidocaine (pharmacological inhibition), the changes were eliminated [11,13,14]. Study of mechanisms related to breathing difficulties should provide insights into how the breathing rhythm works, including occurrence, conduction, and regulation in the peripheral nervous system and CNS. It has been hypothesized that insufficiency of nerve regulation in the sensory and autonomic system may manifest as a dysfunction of the brain in regulating sensory and motor functions, which results in abnormalities in breathing [15].
Obstructive sleep apnea may share similar physiopathological changes with diseases related to the limbic system The forebrain–limbic system has abundant neuronal connections; certain associations among diseases could be related to this system. Accumulating evidence has shown that patients with OSA generally have psychological or psychiatric problems, including excessive sleepiness, irritability, loss of concentration, cognitive deficiency, and depression [16–19]. For instance, clinical symptoms of OSA and depression often occur simultaneously, and treatment of OSA can improve the symptoms of depression as well [20]. In addition, OSA is commonly associated with metabolic syndrome (MS) and obesity [21]. Obesity is known to share some common clinical manifestations, including drowsiness, hypertension, and insulin resistance, which further indicates that these disease states are closely related and links exist between MS and cardiovascular diseases, and they are associated with the limbic system [22–25]. Weaker fMRI signals have also been observed in the gray matter of OSA patients with heart failure. Patients with heart failure often present with high sympathetic and parasympathetic activations. The changes observed in these nerve reactions imply that damage to brain structures induce changes in blood pressure, heart function, and glucose metabolism, all of which are consistent with clinical presentations of OSA. However, it is unclear whether interactions among depression, OSA, and MS increase morbidity and mortality of cardiovascular and cerebrovascular diseases. Such interactions would not be related to heredity; however, they are expected to be associated with insulin resistance. Depression is considered a risk factor of daytime sleepiness, which itself has been correlated with increased BMI, aging, diabetes, smoking, and apneas. Therefore, the limbic system may be associated with OSA, depression, schizophrenia, obesity, and hypertension, and these diseases may share common
Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
Association of OSA with CNS after dysfunction, damage, or trauma Li et al.
neuropathological mechanisms. After the treatment of OSA, for example, the patient’s depression and cognitive function were improved [26,27].
Acknowledgements This article was supported by the National Natural Science Foundation of China, No. V30270502.
12
13
14
15
Conflicts of interest
There are no conflicts of interest.
16
References
17
1
Joo EY, Jeon S, Kim ST, Lee JM, Hong SB. Localized cortical thinning in patients with obstructive sleep apnea syndrome. Sleep 2013; 36: 1153–1162. 2 Santarnecchi E, Sicilia I, Richiardi J, Vatti G, Polizzotto NR, Marino D, et al. Altered cortical and subcortical local coherence in obstructive sleep apnea: a functional magnetic resonance imaging study. J Sleep Res 2013; 22:337–347. 3 Torelli F, Moscufo N, Garreffa G, Placidi F, Romigi A, Zannino S, et al. Cognitive profile and brain morphological changes in obstructive sleep apnea. Neuroimage 2011; 54:787–793. 4 Henderson LA, Woo MA, Macey PM, Macey KE, Frysinger RC, Alger JR, et al. Neural responses during Valsalva maneuvers in obstructive sleep apnea syndrome. J Appl Physiol 2003; 94:1063–1074. 5 Barrera JE. Sleep magnetic resonance imaging: dynamic characteristics of the airway during sleep in obstructive sleep apnea syndrome. Laryngoscope 2011; 121:1327–1335. 6 Harper RM, Macey PM, Henderson LA, Woo MA, Macey KE, Frysinger RC, et al. fMRI responses to cold pressor challenges in control and obstructive sleep apnea subjects. J Appl Physiol 2003; 94:1583–1595. 7 Ahn SH, Kim JH, Kim DU, Choo IS, Lee HJ, Kim HW. Interaction between sleep-disordered breathing and acute ischemic stroke. J Clin Neurol 2013; 9:9–13. 8 Macey KE, Macey PM, Woo MA, Henderson LA, Frysinger RC, Harper PK, et al. Inspiratory loading elicits aberrant fMRI signal changes in obstructive sleep apnea. Respir Physiol Neurobiol 2006; 151:44–60. 9 Oades RD, Halliday GM. Ventral tegmental (A10) system: neurobiology. 1. Anatomy and connectivity. Brain Res 1987; 434:117–165. 10 Cersosimo MG, Benarroch EE. Central control of autonomic function and involvement in neurodegenerative disorders. Handb Clin Neurol 2013; 117:45–57. 11 Pohl A, Anders S, Schulte-Ru¨ther M, Mathiak K, Kircher T. Positive facial affect – an fMRI study on the involvement of insula and amygdala. PLoS One 2013; 8:e69886.
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Cui L, Wang JH, Wang M, Huang M, Wang CY, Xia H, et al. Injection of L-glutamate into the insular cortex produces sleep apnea and serotonin reduction in rats. Sleep Breath 2012; 16:845–853. Wang M, Lin W, Wang J, Huang M, Wang C, Li M, et al. 5-hydroxytryptaminemediated apnea caused by the habenular nucleus. Neural Regen Res 2011; 6:1554–1558. Li M, Wang J, Huang M, Lin W, Wang M, Yu L, et al. Blockage of the habenular nucleus can eliminate dyspnea induced by electrostimulation of the insular cortex. Neural Regen Res 2010; 5:1025–1029. Macefield VG, Gandevia SC, Henderson LA. Neural sites involved in the sustained increase in muscle sympathetic nerve activity induced by inspiratory capacity apnea: a fMRI study. J Appl Physiol 2006; 100:266–273. Twigg GL, Papaioannou I, Jackson M, Ghiassi R, Shaikh Z, Jaye J, et al. Obstructive sleep apnea syndrome is associated with deficits in verbal but not visual memory. Am J Respir Crit Care Med 2010; 182:98–103. Rakel RE. Clinical and societal consequences of obstructive sleep apnea and excessive daytime sleepiness. Postgrad Med 2009; 121:86–95. Halbower AC, Degaonkar M, Barker PB, Earley CJ, Marcus CL, Smith PL, et al. Childhood obstructive sleep apnea associates with neuropsychological deficits and neuronal brain injury. PLoS Med 2006; 3:e301. Dominici M, Gomes Mda M. Obstructive sleep apnea (OSA) and depressive symptoms. Arq Neuropsiquiatr 2009; 67:35–39. Feng J, Chen BY, Chiang AA. Significance of depression in obstructive sleep apnea patients and the relationship between the comorbidity and continuous positive airway pressure treatment. Chin Med J (Engl) 2010; 123:1596–1602. Mariani S, Fiore D, Barbaro G, Basciani S, Saponara M, D’Arcangelo E, et al. Association of epicardial fat thickness with the severity of obstructive sleep apnea in obese patients. Int J Cardiol 2013; 167:2244–2249. Papanas N, Steiropoulos P, Nena E, Tzouvelekis A, Skarlatos A, Konsta M, et al. Predictors of obstructive sleep apnea in males with metabolic syndrome. Vasc Health Risk Manag 2010; 6:281–286. Knight WD, Little JT, Carreno FR, Toney GM, Mifflin SW, Cunningham JT. Chronic intermittent hypoxia increases blood pressure and expression of FosB/DeltaFosB in central autonomic regions. Am J Physiol Regul Integr Comp Physiol 2011; 301:R131–R139. Rubin RR, Gaussoin SA, Peyrot M, DiLillo V, Miller K, Wadden TA, et al. Cardiovascular disease risk factors, depression symptoms and antidepressant medicine use in the Look AHEAD (Action for Health in Diabetes) clinical trial of weight loss in diabetes. Diabetologia 2010; 53:1581–1589. Jean-Louis G, Zizi F, Brown D, Ogedegbe G, Borer J, McFarlane S. Obstructive sleep apnea and cardiovascular disease: evidence and underlying mechanisms. Minerva Pneumol 2009; 48:277–293. Bixler EO, Vgontzas AN, Lin HM, Calhoun SL, Vela-Bueno A, Kales A. Excessive daytime sleepiness in a general population sample: the role of sleep apnea, age, obesity, diabetes, and depression. J Clin Endocrinol Metab 2005; 90:4510–4515. Cross RL, Kumar R, Macey PM, Doering LV, Alger JR, Yan-Go FL, et al. Neural alterations and depressive symptoms in obstructive sleep apnea patients. Sleep 2008; 31:1103–1109.
Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
