Zhang, Jiaxing, Ji Chen, Cunxiu Fan, Jinqiang Li, Jianzhong Lin, Tianhe Yang, and Ming Fan. Alteration of spontaneous brain activity after hypoxia-reoxygenation: A resting-state fMRI study. High Alt Med Biol. 18:20–26, 2017.—The present study was designed to investigate the effect of hypoxia–reoxygenation on the spontaneous neuronal activity in brain. Sixteen sea-level (SL) soldiers (20.5 ± 0.7 years), who garrisoned the frontiers in high altitude (HA) (2300–4400 m) for two years and subsequently descended to sea level for one to seven days, were recruited. Control group consisted of 16 matched SL natives. The amplitude of low-frequency fluctuations (ALFF) of regional brain functional magnetic resonance imaging signal in resting state and functional connectivity (FC) between brain regions was analyzed. HA subjects showed significant increases of ALFF at several sites within the bilateral occipital cortices and significant decreases of ALFF in the right anterior insula and extending to the caudate, putamen, inferior frontal orbital cortex, temporal pole, and superior temporal gyrus; lower ALFF values in the right insula were positively correlated with low respiratory measurements. The right insula in HA subjects had increases of FC with the right superior temporal gyrus, postcentral gyrus, rolandic operculum, supramarginal gyrus, and inferior frontal triangular area. We thus demonstrated that hypoxia–reoxygenation had influence on the spontaneous neuronal activity in brain. The decrease of insular neuronal activity may be related to the reduction of ventilatory drive, while the increase of FC with insula may indicate a central compensation.
Get full access to this article
View all access options for this article.
References
1.
AlexandrovVG, IvanovaTG, and AlexandrovaNP. (2007). Prefrontal control of respiration. J Physiol Pharmacol, 58:17–23.
2.
Alonso-CalviñoE, Martínez-CameroI, Fernández-LópezE, Humanes-ValeraD, FoffaniG, and AguilarJ. (2016). Increased responses in the somatosensory thalamus immediately after spinal cord injury. Neurobiol Dis, 87:39–49.
3.
Andrews-HannaJR, SnyderAZ, VincentJL, et al. (2007). Disruption of large-scale brain systems in advanced aging. Neuron, 56:924–935.
4.
AugustineJR. (1996). Circuitry and functional aspects of the insular lobe in primates including humans. Brain Res Rev, 22:229–244.
5.
BinksAP, EvansKC, ReedJD, MoosaviSH, and BanzettRB. (2014). The time-course of cortico-limbic neural responses to air hunger. Respir Physiol Neurobiol, 204:78–85.
6.
BiswalB, YetkinFZ, HaughtonVM, and HydeJS. (1995). Functional connectivity in the motor cortex of resting human brain using echo-planar MRI. Magn Reson Med, 34:537–541.
7.
BowmanBR, KumarNN, HassanSF, McMullanS, and GoodchildAK. (2013). Brain sources of inhibitory input to the rat rostral ventrolateral medulla. J Comp Neurol, 521:213–232.
8.
CaudaF, D'AgataF, SaccoK, DucaS, GeminianiG, and VercelliA. (2011). Functional connectivity of the insula in the resting brain. Neuroimage, 55:8–23.
9.
ChenJ, FanC, LiJ, HanQ, LinJ, YangT, and ZhangJ. (2016). Increased intraregional synchronized neural activity in adult brain after prolonged adaptation to high-altitude hypoxia: A resting-state fMRI study. High Alt Med Biol, 17:16–24.
10.
CordesD, HaughtonVM, ArfanakisK, et al. (2001). Frequencies contributing to functional connectivity in the cerebral cortex in “resting-state” data. AJNR Am J Neuroradiol, 22:1326–1333.
11.
CuiL, WangJH, WangM, et al. (2012). Injection of L-glutamate into the insular cortex produces sleep apnea and serotonin reduction in rats. Sleep Breath, 16:845–853.
12.
DavenportPW, and VovkA. (2009). Cortical and subcortical central neural pathways in respiratory sensations. Respir Physiol Neurobiol, 167:72–86.
13.
EvansKC, DoughertyDD, SchmidAM, et al. (2009). Modulation of spontaneous breathing via limbic/paralimbic-bulbar circuitry: An event-related fMRI study. Neuroimage, 47:961–971.
14.
EvansKC. (2010). Cortico-limbic circuitry and the airways: Insights from functional neuroimaging of respiratory afferents and efferents. Biol Psychol, 84:13–25.
15.
FryerSL, RoachBJ, FordJM, et al. (2015). Relating intrinsic low-frequency BOLD cortical oscillations to cognition in schizophrenia. Neuropsychopharmacology, 40:2705–2714.
16.
FukushiI, TakedaK, YokotaS, et al. (2016). Effects of arundic acid, an astrocytic modulator, on the cerebral and respiratory functions in severe hypoxia. Respir Physiol Neurobiol, 226:24–29.
17.
GaoL, BaiL, ZhangY, et al. (2015). Frequency-dependent changes of local resting oscillations in sleep-deprived brain. PLoS One, 10:e0120323.
18.
GavelloD, Rojo-RuizJ, MarcantoniA, FranchinoC, CarboneE, and CarabelliV. (2012). Leptin counteracts the hypoxia-induced inhibition of spontaneously firing hippocampal neurons: A microelectrode array study. PLoS One, 7:e41530.
19.
GaytanSP, and PasaroR. (1998). Connections of the rostral ventral respiratory neuronal cell group: An anterograde and retrograde tracing study in the rat. Brain Res Bull, 47:625–642.
20.
GoodallS, TwomeyR, and AmannM. (2014). Acute and chronic hypoxia: Implications for cerebral function and exercise tolerance. Fatigue, 2:73–92.
21.
HarperRM, KumarR, MaceyPM, HarperRK, and OgrenJA. (2015). Impaired neural structure and function contributing to autonomic symptoms in congenital central hypoventilation syndrome. Front Neurosci, 9:415.
22.
HarrisAD, MurphyK, DiazCM, et al. (2013). Cerebral blood flow response to acute hypoxic hypoxia. Nmr Biomed, 26:1844–1852.
23.
HerigstadM, HayenA, WiechK, and PattinsonKT. (2011). Dyspnoea and the brain. Respir Med, 105:809–817.
24.
HermannDM, SiccoliM, KirovP, GuggerM, and BassettiCL. (2007). Central periodic breathing during sleep in acute ischemic stroke. Stroke, 38:1082–1084.
25.
HoptmanMJ, ZuoXN, ButlerPD, et al. (2010). Amplitude of low-frequency oscillations in schizophrenia: A resting state fMRI study. Schizophr Res, 117:13–20.
26.
ItoJ, RoyS, LiuY, et al. (2014). Whisker barrel cortex delta oscillations and gamma power in the awake mouse are linked to respiration. Nat Commun, 5:3572.
27.
LacueyN, ZonjyB, KahrimanES, et al. (2016). Homotopic reciprocal functional connectivity between anterior human insulae. Brain Struct Funct, 221:2695–2701.
28.
LaMannaJC, ChavezJC, and PichiuleP. (2004). Structural and functional adaptation to hypoxia in the rat brain. J Exp Biol, 207:3163–3169.
29.
LoisJH, RiceCD, and YatesBJ. (2009). Neural circuits controlling diaphragm function in the cat revealed by transneuronal tracing. J Appl Physiol (1985), 106:138–152.
30.
MaceyKE, MaceyPM, WooMA, et al. (2004). fMRI signal changes in response to forced expiratory loading in congenital central hypoventilation syndrome. J Appl Physiol, 97:1897–1907.
31.
MukandalaG, TynanR, LaniganS, and O'ConnorJJ. (2016). The effects of hypoxia and inflammation on synaptic signaling in the CNS. Brain Sci, 6:pii: E6.
32.
OgohS, SatoK, NakaharaH, OkazakiK, SubudhiAW, and MiyamotoT. (2013). Effect of acute hypoxia on blood flow in vertebral and internal carotid arteries. Exp Physiol, 98:692–698.
33.
ParshallMB, SchwartzsteinRM, AdamsL, et al. (2012). An official American Thoracic Society statement: Update on the mechanisms, assessment, and management of dyspnea. Am J Respir Crit Care Med, 185:435–452.
34.
PenaF, and RamirezJM. (2005). Hypoxia-induced changes in neuronal network properties. Mol Neurobiol, 32:251–283.
35.
QiR, LiuC, KeJet al. (2016). Intrinsic brain abnormalities in irritable bowel syndrome and effect of anxiety and depression. Brain Imaging Behav, 10:1127–1134.
36.
RaichleME. (2006). Neuroscience. The brain's dark energy. Science, 314:1249–1250.
37.
RomanoSA, PietriT, Pérez-SchusterV, JouaryA, HaudrechyM, and SumbreG. (2015). Spontaneous neuronal network dynamics reveal circuit's functional adaptations for behavior. Neuron, 85:1070–1085.
38.
RostrupE, LarssonHB, BornAP, KnudsenGM, and PaulsonOB. (2005). Changes in BOLD and ADC weighted imaging in acute hypoxia during sea-level and altitude adapted states. Neuroimage, 28:947–955.
39.
SadaghianiS, and KleinschmidtA. (2013). Functional interactions between intrinsic brain activity and behavior. Neuroimage, 80:379–386.
40.
SchiffSJ, and SomjenGG. (1985). Hyperexcitability following moderate hypoxia in hippocampal tissue slices. Brain Res, 337:337–340.
41.
SicardKM, and DuongTQ. (2005). Effects of hypoxia, hyperoxia, and hypercapnia on baseline and stimulus-evoked BOLD, CBF, and CMRO2 in spontaneously breathing animals. Neuroimage, 25:850–858.
42.
SuiJ, HusterR, YuQ, SegallJM, and CalhounVD. (2014). Function-structure associations of the brain: Evidence from multimodal connectivity and covariance studies. Neuroimage, 102:11–23.
43.
TanAY. (2015). Spatial diversity of spontaneous activity in the cortex. Front Neural Circuits, 9:48.
44.
Vigneau-RoyN, BernierM, DescoteauxM, and WhittingstallK. (2014). Regional variations in vascular density correlate with resting-state and task-evoked blood oxygen level-dependent signal amplitude. Hum Brain Mapp, 35:1906–1920.
45.
VisintinE, De PanfilisC, AntonucciC, CapecciC, MarchesiC, and SambataroF. (2015). Parsing the intrinsic networks underlying attention: A resting state study. Behav Brain Res, 278:315–322.
46.
WangL, WangT, LiuS, et al. (2014). Cerebral anatomical changes in female asthma patients with and without depression compared to healthy controls and patients with depression. J Asthma, 51:927–933.
47.
WatanabeT, HiroseS, WadaH, et al. (2014). Energy landscapes of resting-state brain networks. Front Neuroinform, 8:12.
48.
WhittingtonMA, TraubRD, FaulknerHJ, StanfordIM, and JefferysJG. (1997). Recurrent excitatory postsynaptic potentials induced by synchronized fast corticaloscillations. Proc Natl Acad Sci U S A, 94:12198–12203.
49.
WillieCK, MacleodDB, ShawAD, et al. (2012). Regional brain blood flow in man during acute changes in arterial blood gases. J Physiol, 590:3261–3275.
50.
WróbelA. (2000). Beta activity: A carrier for visual attention. Acta Neurobiol Exp (Wars), 60: 247–260.
51.
YanX, ZhangJ, GongQ, and WengX. (2011). Cerebrovascular reactivity among native-raised high altitude residents: An fMRI study. BMC Neurosci, 12:94.
52.
YangZ, QiuJ, WangP, LiuR, and ZuoXN. (2016). Brain structure-function associations identified in large-scale neuroimaging data. Brain Struct Funct; [Epub ahead of print].
53.
ZangYF, HeY, ZhuCZ, et al. (2007). Altered baseline brain activity in children with ADHD revealed by resting-state functional MRI. Brain Dev, 29:83–91.
54.
ZhangJ, YanX, ShiJ, GongQ, WengX, and LiuY. (2010). Structural modifications of the brain in acclimatization to high-altitude. PLoS One, 5:e11449.
55.
ZhangJ, ZhangH, LiJ, et al. (2013). Adaptive modulation of adult brain gray and white matter to high altitude: Structural MRI studies. PLoS One, 8:e68621.
56.
ZhangJX, ChenXQ, DuJZ, ChenQM, and ZhuCY. (2005). Neonatal exposure to intermittent hypoxia enhances mice performance in water maze and 8-arm radial maze tasks. J Neurobiol, 65:72–84.
57.
ZhaoJ, ZhangR, YuQ, and ZhangJ. (2016). Characteristics of EEG activity during high altitude hypoxia and lowland reoxygenation. Brain Res, 1648:243–249.
58.
ZhouQ, YangS, LuoY, QiY, YanZ, ShiZ, and FanY. (2012). A randomly-controlled study on the cardiac function at the early stage of return to the plains after short-term exposure to high altitude. PLoS One, 7:e31097.
59.
ZuoXN, Di MartinoA, KellyC, et al. (2010). The oscillating brain: Complex and reliable. Neuroimage, 49:1432–1445.
Supplementary Material
Please find the following supplemental material available below.
For Open Access articles published under a Creative Commons License, all supplemental material carries the same license as the article it is associated with.
For non-Open Access articles published, all supplemental material carries a non-exclusive license, and permission requests for re-use of supplemental material or any part of supplemental material shall be sent directly to the copyright owner as specified in the copyright notice associated with the article.
