High-altitude exposure alters the coupling among core large-scale brain networks: a multi-altitude rs-fMRI study

Abstract

The impact of high-altitude environments on the three core large-scale brain networks (default mode network (DMN), executive control network (ECN), and salience network (SN)) remains poorly understood. This study included 64 ultra-high-altitude residents (U-HA, 3600 m), 51 high-altitude residents (HA, 1500 m), and 49 low-altitude residents (LA, 400 m). Large-scale networks (DMN, SN, and bilateral ECN) were identified by group independent component analysis. The within- and between-network functional connectivity (FC) was quantified. Groups were compared using one-way analysis of variance. Partial correlations assessed the associations between network FC and oxygen saturation and HA residence duration after controlling confounders. The HA and U-HA groups exhibited higher medial prefrontal cortex (mPFC)-left posterior parietal cortex (PPC)/right dorsolateral prefrontal cortex (dlPFC), posterior cingulate cortex (PCC)-right anterior insula (AI), left and right dlPFC, and left dlPFC-dorsal anterior cingulate cortex (dACC) FC than the LA group (FDR-corrected, LSD post hoc). The blood oxygen saturation negatively correlated with the above FC, surviving correction for age, sex, education, and motion. Our findings may indicate that HA hypoxia is associated with reduced functional segregation between the DMN and ECN, as well as enhanced coupling of the bilateral ECN and SN-ECN.

Keywords

high altitude / default mode network / executive control network / salience network / functional magnetic resonance imaging

References

[1] Tremblay JC , Ainslie PN . Global and country-level estimates of human population at high altitude. Proc Natl Acad Sci USA 2021; 118(18): e2102463118

[2] Nuss R . Medical conditions and high-altitude travel. N Engl J Med 2022; 386(19): 1866–1867

[3] McMorris T , Hale BJ , Barwood M , Costello J , Corbett J. . Effect of acute hypoxia on cognition: a systematic review and meta-regression analysis.. Neurosci Biobehav Rev 2017; 74(Pt A): 225–232

[4] Griva K , Stygall J , Wilson MH , Martin D , Levett D , Mitchell K , Mythen M , Montgomery HE , Grocott MP , Aref-Adib G , Edsell M , Plant T , Imray C , Cooke D , Harrington J , Khosravi M , Newman SP , for the Caudwell Xtreme Everest Research Group . Caudwell Xtreme Everest: a prospective study of the effects of environmental hypoxia on cognitive functioning. PLoS One 2017; 12(3): e0174277

[5] Zhang X , Zhang J . The human brain in a high altitude natural environment: a review. Front Hum Neurosci 2022; 16: 915995

[6] Zhang J , Chen J , Fan C , Li J , Lin J , Yang T , Fan M . Alteration of spontaneous brain activity after hypoxia-reoxygenation: a resting-state fMRI study. High Alt Med Biol 2017; 18(1): 20–26

[7] Chen X , Liu J , Wang J , Xin Z , Zhang Q , Zhang W , Xi Y , Zhu Y , Li C , Li J , Han Y , Liu J , Li B , Luo W , Chen J . Altered resting-state networks may explain the executive impairment in young health immigrants into high-altitude area. Brain Imaging Behav 2021; 15(1): 147–156

[8] Chen J , Wang S , Li Z , Li Y , Huang P , Zhu J , Wang F , Li Y , Liu W , Xue J , Shi H , Li W , Liang Z , Wang W , Li Q . The effect of long-term methadone maintenance treatment on coupling among three large-scale brain networks in male heroin-dependent individuals: A resting-state fMRI study. Drug Alcohol Depend 2022; 238: 109549

[9] Menon V . Large-scale brain networks and psychopathology: a unifying triple network model. Trends Cogn Sci 2011; 15(10): 483–506

[10] Menon V . The triple network model, insight, and large-scale brain organization in autism. Biol Psychiatry 2018; 84(4): 236–238

[11] Ge R , Downar J , Blumberger DM , Daskalakis ZJ , Vila-Rodriguez F . Functional connectivity of the anterior cingulate cortex predicts treatment outcome for rTMS in treatment-resistant depression at 3-month follow-up. Brain Stimul 2020; 13(1): 206–214

[12] Li Q , Liu J , Wang W , Wang Y , Li W , Chen J , Zhu J , Yan X , Li Y , Li Z , Ye J , Wang W . Disrupted coupling of large-scale networks is associated with relapse behaviour in heroin-dependent men. J Psychiatry Neurosci 2018; 43(1): 48–57

[13] Bressler SL , Menon V . Large-scale brain networks in cognition: emerging methods and principles. Trends Cogn Sci 2010; 14(6): 277–290

[14] Menon V , D’Esposito M . The role of PFC networks in cognitive control and executive function. Neuropsychopharmacology 2022; 47(1): 90–103

[15] Jin L , Yuan M , Chen J , Zhang W , Wang L , Wei Y , Li Y , Guo Z , Wang W , Wei L , Li Q . Abnormal cerebral metabolism and metabolic connectivity in individuals with heroin dependence: an integrated resting-state PET/fMRI study in large-scale networks. J Psychiatry Neurosci 2023; 48(4): E295–E304

[16] Lerman C , Gu H , Loughead J , Ruparel K , Yang Y , Stein EA . Large-scale brain network coupling predicts acute nicotine abstinence effects on craving and cognitive function. JAMA Psychiatry 2014; 71(5): 523–530

[17] Raichle ME , MacLeod AM , Snyder AZ , Powers WJ , Gusnard DA , Shulman GL . A default mode of brain function. Proc Natl Acad Sci USA 2001; 98(2): 676–682

[18] Lindquist KA , Barrett LF . A functional architecture of the human brain: emerging insights from the science of emotion. Trends Cogn Sci 2012; 16(11): 533–540

[19] Schimmelpfennig J , Topczewski J , Zajkowski W , Jankowiak-Siuda K . The role of the salience network in cognitive and affective deficits. Front Hum Neurosci 2023; 17: 1133367

[20] Chen AC , Oathes DJ , Chang C , Bradley T , Zhou ZW , Williams LM , Glover GH , Deisseroth K , Etkin A . Causal interactions between fronto-parietal central executive and default-mode networks in humans. Proc Natl Acad Sci USA 2013; 110(49): 19944–19949

[21] Fox MD , Snyder AZ , Vincent JL , Corbetta M , Van Essen DC , Raichle ME . The human brain is intrinsically organized into dynamic, anticorrelated functional networks. Proc Natl Acad Sci USA 2005; 102(27): 9673–9678

[22] Uddin LQ , Menon V . The anterior insula in autism: under-connected and under-examined. Neurosci Biobehav Rev 2009; 33(8): 1198–1203

[23] Sadaghiani S , Kleinschmidt A . Functional interactions between intrinsic brain activity and behavior. Neuroimage 2013; 80: 379–386

[24] Zerbi V , Floriou-Servou A , Markicevic M , Vermeiren Y , Sturman O , Privitera M , von Ziegler L , Ferrari KD , Weber B , De Deyn PP , Wenderoth N , Bohacek J. . Rapid reconfiguration of the functional connectome after chemogenetic locus coeruleus activation.. Neuron 2019; 103(4): 702–718.e5

[25] Ng KK , Lo JC , Lim JKW , Chee MWL , Zhou J . Reduced functional segregation between the default mode network and the executive control network in healthy older adults: a longitudinal study. Neuroimage 2016; 133: 321–330

[26] Archer JA , Lee A , Qiu A , Chen SH . A comprehensive analysis of connectivity and aging over the adult life span. Brain Connect 2016; 6(2): 169–185

[27] Yeo BT , Tandi J , Chee MW . Functional connectivity during rested wakefulness predicts vulnerability to sleep deprivation. Neuroimage 2015; 111: 147–158

[28] Ng KK , Qiu Y , Lo JC , Koay ES , Koh WP , Chee MW , Zhou J . Functional segregation loss over time is moderated by APOE genotype in healthy elderly. Hum Brain Mapp 2018; 39(7): 2742–2752

[29] Marek S , Dosenbach NUF . The frontoparietal network: function, electrophysiology, and importance of individual precision mapping. Dialogues Clin Neurosci 2018; 20(2): 133–140

[30] Brunoni AR , Vanderhasselt MA . Working memory improvement with non-invasive brain stimulation of the dorsolateral prefrontal cortex: a systematic review and meta-analysis. Brain Cogn 2014; 86: 1–9

[31] Virués-Ortega J , Bucks R , Kirkham FJ , Baldeweg T , Baya-Botti A , Hogan AM , on behalf of Bolivian Children Living at Altitude project (BoCLA 06) . Changing patterns of neuropsychological functioning in children living at high altitude above and below 4000 m: a report from the Bolivian Children Living at Altitude (BoCLA) study. Dev Sci 2011; 14(5): 1185–1193

[32] Rimoldi SF , Rexhaj E , Duplain H , Urben S , Billieux J , Allemann Y , Romero C , Ayaviri A , Salinas C , Villena M , Scherrer U , Sartori C . Acute and chronic altitude-induced cognitive dysfunction in children and adolescents. J Pediatr 2016; 169: 238–243

[33] Sharma VK , Das SK , Dhar P , Hota KB , Mahapatra BB , Vashishtha V , Kumar A , Hota SK , Norboo T , Srivastava RB . Domain specific changes in cognition at high altitude and its correlation with hyperhomocysteinemia. PLoS One 2014; 9(7): e101448

[34] Koski L , Paus T . Functional connectivity of the anterior cingulate cortex within the human frontal lobe: a brain-mapping meta-analysis. Exp Brain Res 2000; 133(1): 55–65

[35] Noël X , Brevers D , Bechara A . A neurocognitive approach to understanding the neurobiology of addiction. Curr Opin Neurobiol 2013; 23(4): 632–638

[36] Nyberg L. . Cognitive control in the prefrontal cortex: a central or distributed executive?. Scand J Psychol 2018; 59(1): 62–65

[37] Cai X , Li G , Liu Q , Xiao F , Zhang Y , Wang Y . The neural mechanisms of cognitive control in the category induction task. Front Psychol 2022; 13: 743178

[38] Schulz KP , Bedard AV , Czarnecki R , Fan J . Preparatory activity and connectivity in dorsal anterior cingulate cortex for cognitive control. Neuroimage 2011; 57(1): 242–250

[39] Park M , Jung MH , Lee J , Choi AR , Chung SJ , Kim B , Kim DJ , Choi JS . Neurophysiological and cognitive correlates of error processing deficits in internet gaming disorder. Cereb Cortex 2020; 30(9): 4914–4921

[40] Le TM , Zhang S , Zhornitsky S , Wang W , Li CR . Neural correlates of reward-directed action and inhibition of action. Cortex 2020; 123: 42–56

[41] Yitao L , Lv Z , Xin W , Yongchen F , Ying W . Dynamic brain functional states associated with inhibition control under different altitudes. Cogn Neurodyn 2024; 18(4): 1931–1941

RIGHTS & PERMISSIONS

Higher Education Press