{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T12:12:08Z","timestamp":1792671128700,"version":"4.5.0"},"reference-count":86,"publisher":"National Academy of Sciences","issue":"28","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2011,7,12]]},"abstract":"<jats:p>One of the most intriguing recent discoveries concerning brain function is that intrinsic neuronal activity manifests as spontaneous fluctuations of the blood oxygen level\u2013dependent (BOLD) functional MRI signal. These BOLD fluctuations exhibit temporal synchrony within widely distributed brain regions known as resting-state networks. Resting-state networks are present in the waking state, during sleep, and under general anesthesia, suggesting that spontaneous neuronal activity plays a fundamental role in brain function. Despite its ubiquitous presence, the physiological role of correlated, spontaneous neuronal activity remains poorly understood. One hypothesis is that this activity is critical for the development of synaptic connections and maintenance of synaptic homeostasis. We had a unique opportunity to test this hypothesis in a 5-y-old boy with severe epileptic encephalopathy. The child developed marked neurologic dysfunction in association with a seizure disorder, resulting in a 1-y period of behavioral regression and progressive loss of developmental milestones. His EEG showed a markedly abnormal pattern of high-amplitude, disorganized slow activity with frequent generalized and multifocal epileptiform discharges. Resting-state functional connectivity MRI showed reduced BOLD fluctuations and a pervasive lack of normal connectivity. The child underwent successful corpus callosotomy surgery for treatment of drop seizures. Postoperatively, the patient's behavior returned to baseline, and he resumed development of new skills. The waking EEG revealed a normal background, and functional connectivity MRI demonstrated restoration of functional connectivity architecture. These results provide evidence that intrinsic, coherent neuronal signaling may be essential to the development and maintenance of the brain's functional organization.<\/jats:p>","DOI":"10.1073\/pnas.1109144108","type":"journal-article","created":{"date-parts":[[2011,6,28]],"date-time":"2011-06-28T05:22:51Z","timestamp":1309238571000},"page":"11638-11643","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":149,"title":["Resting-state activity in development and maintenance of normal brain function"],"prefix":"10.1073","volume":"108","author":[{"given":"Carolyn E.","family":"Pizoli","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Duke University Medical Center, Durham, NC 27110; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manish N.","family":"Shah","sequence":"additional","affiliation":[{"name":"Departments of bNeurological Surgery,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abraham Z.","family":"Snyder","sequence":"additional","affiliation":[{"name":"Neurology,"},{"name":"Radiology,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua S.","family":"Shimony","sequence":"additional","affiliation":[{"name":"Radiology,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David D.","family":"Limbrick","sequence":"additional","affiliation":[{"name":"Departments of bNeurological Surgery,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcus E.","family":"Raichle","sequence":"additional","affiliation":[{"name":"Neurology,"},{"name":"Radiology,"},{"name":"Biomedical Engineering,"},{"name":"Anatomy and Neurobiology, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bradley L.","family":"Schlaggar","sequence":"additional","affiliation":[{"name":"Neurology,"},{"name":"Radiology,"},{"name":"Anatomy and Neurobiology, and"},{"name":"Pediatrics, Washington University School of Medicine, St. Louis, MO 63110"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew D.","family":"Smyth","sequence":"additional","affiliation":[{"name":"Departments of bNeurological Surgery,"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2011,6,27]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0193(1998)6:4<239::AID-HBM4>3.0.CO;2-4"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1002\/mrm.1910340409"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0905267106"},{"key":"e_1_3_3_4_2","first-page":"8","article-title":"Advances and pitfalls in the analysis and interpretation of resting-state FMRI data","volume":"4","author":"Cole DM","year":"2010","unstructured":"DM Cole, SM Smith, CF Beckmann, Advances and pitfalls in the analysis and interpretation of resting-state FMRI data. Front Syst Neurosci 4, 8 (2010).","journal-title":"Front Syst Neurosci"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0911855107"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1002\/mrm.21524"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature05758"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.5709-09.2010"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1007921107"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0811221106"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1093\/cercor\/bhq035"},{"key":"e_1_3_3_12_2","first-page":"10","article-title":"Maturing thalamocortical functional connectivity across development","volume":"4","author":"Fair DA","year":"2010","unstructured":"DA Fair, et al., Maturing thalamocortical functional connectivity across development. Front Syst Neurosci 4, 10 (2010).","journal-title":"Front Syst Neurosci"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0705843104"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0704380104"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1093\/cercor\/bhq071"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropsychologia.2006.06.017"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0901435106"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0900924106"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1002\/hbm.20537"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0014224"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1002\/hbm.20580"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1038\/nn.2177"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0807010105"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2008.12.066"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.neuro.29.051605.112819"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tics.2010.01.008"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2006.10.041"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.3389\/fnsys.2010.00021"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2010.04.009"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1003109107"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1157.1997.tb01136.x"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1207\/s15374424jccp2603_6"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1093\/jpepsy\/9.2.219"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1352\/0895-8017(2008)113[178:MCFAFT]2.0.CO;2"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.5664\/jcsm.26819"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1055\/s-0028-1091786"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.3171\/2010.5.PEDS1029"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.0013-9580.2005.461009.x"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1528-1157.2001.042suppl.3023.x"},{"key":"e_1_3_3_40_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.yebeh.2007.06.001"},{"key":"e_1_3_3_41_2","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awq183"},{"key":"e_1_3_3_42_2","doi-asserted-by":"crossref","first-page":"2312","DOI":"10.1111\/j.1528-1167.2007.01195.x","article-title":"Different neuronal networks are associated with spikes and slow activity in hypsarrhythmia","volume":"48","author":"Siniatchkin M","year":"2007","unstructured":"M Siniatchkin, et al., Different neuronal networks are associated with spikes and slow activity in hypsarrhythmia. Epilepsia 48, 2312\u20132321 (2007).","journal-title":"Epilepsia"},{"key":"e_1_3_3_43_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0404.2007.00808.x"},{"key":"e_1_3_3_44_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-8749.1997.tb07462.x"},{"key":"e_1_3_3_45_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.0013-9580.2005.03504.x"},{"key":"e_1_3_3_46_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.0013-9580.2004.30503.x"},{"key":"e_1_3_3_47_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1528-1157.2001.05403.x"},{"key":"e_1_3_3_48_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.yebeh.2008.04.020"},{"key":"e_1_3_3_49_2","first-page":"85","article-title":"EEG patterns after callosotomy","volume":"41","author":"Quattrini A","year":"1997","unstructured":"A Quattrini, et al., EEG patterns after callosotomy. J Neurosurg Sci 41, 85\u201392 (1997).","journal-title":"J Neurosurg Sci"},{"key":"e_1_3_3_50_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0573-08.2008"},{"key":"e_1_3_3_51_2","doi-asserted-by":"publisher","DOI":"10.1097\/WNR.0b013e3282fb8203"},{"key":"e_1_3_3_52_2","first-page":"18","article-title":"Identifying basal ganglia divisions in individuals using resting-state functional connectivity MRI","volume":"4","author":"Barnes KA","year":"2010","unstructured":"KA Barnes, et al., Identifying basal ganglia divisions in individuals using resting-state functional connectivity MRI. Front Syst Neurosci 4, 18 (2010).","journal-title":"Front Syst Neurosci"},{"key":"e_1_3_3_53_2","doi-asserted-by":"publisher","DOI":"10.1093\/cercor\/bhn041"},{"key":"e_1_3_3_54_2","doi-asserted-by":"publisher","DOI":"10.1152\/jn.90463.2008"},{"key":"e_1_3_3_55_2","doi-asserted-by":"publisher","DOI":"10.1093\/cercor\/bhp135"},{"key":"e_1_3_3_56_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00429-009-0208-6"},{"key":"e_1_3_3_57_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tics.2008.01.001"},{"key":"e_1_3_3_58_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.schres.2009.09.030"},{"key":"e_1_3_3_59_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2009.03.024"},{"key":"e_1_3_3_60_2","first-page":"19","article-title":"Clinical applications of resting state functional connectivity","volume":"4","author":"Fox MD","year":"2010","unstructured":"MD Fox, M Greicius, Clinical applications of resting state functional connectivity. Front Syst Neurosci 4, 19 (2010).","journal-title":"Front Syst Neurosci"},{"key":"e_1_3_3_61_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrneurol.2009.198"},{"key":"e_1_3_3_62_2","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awq075"},{"key":"e_1_3_3_63_2","doi-asserted-by":"publisher","DOI":"10.1177\/0883073894009001131"},{"key":"e_1_3_3_64_2","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410210104"},{"key":"e_1_3_3_65_2","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410210105"},{"key":"e_1_3_3_66_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.58.11.1646"},{"key":"e_1_3_3_67_2","doi-asserted-by":"publisher","DOI":"10.1017\/S001216220100175X"},{"key":"e_1_3_3_68_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1160809"},{"key":"e_1_3_3_69_2","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awm121"},{"key":"e_1_3_3_70_2","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awq043"},{"key":"e_1_3_3_71_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0902455106"},{"key":"e_1_3_3_72_2","doi-asserted-by":"publisher","DOI":"10.1093\/cercor\/bhp270"},{"key":"e_1_3_3_73_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.274.5290.1133"},{"key":"e_1_3_3_74_2","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2008.157222"},{"key":"e_1_3_3_75_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.conb.2009.05.012"},{"key":"e_1_3_3_76_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrn1327"},{"key":"e_1_3_3_77_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1167.2006.00894.x"},{"key":"e_1_3_3_78_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1157.1988.tb05797.x"},{"key":"e_1_3_3_79_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.5516-09.2010"},{"key":"e_1_3_3_80_2","doi-asserted-by":"publisher","DOI":"10.1152\/jn.90777.2008"},{"key":"e_1_3_3_81_2","doi-asserted-by":"publisher","DOI":"10.1002\/hbm.460030305"},{"key":"e_1_3_3_82_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2004.06.018"},{"key":"e_1_3_3_83_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2006.04.031"},{"key":"e_1_3_3_84_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0604187103"},{"key":"e_1_3_3_85_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0504136102"},{"key":"e_1_3_3_86_2","doi-asserted-by":"publisher","DOI":"10.1109\/72.761722"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.1109144108","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,4,8]],"date-time":"2024-04-08T02:41:13Z","timestamp":1712544073000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.1109144108"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2011,6,27]]},"references-count":86,"journal-issue":{"issue":"28","published-print":{"date-parts":[[2011,7,12]]}},"alternative-id":["10.1073\/pnas.1109144108"],"URL":"https:\/\/doi.org\/10.1073\/pnas.1109144108","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.11819956.12916054","asserted-by":"object"}]},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2011,6,27]]},"assertion":[{"value":"2011-06-27","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}