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Hypercapnia is known to have clear impact on brain hemodynamics through vasodilation, but have unclear effect on neuronal activity. This study investigates the effect of hypercapnia on brain homotopy, achieved by breathing 5% carbon dioxide (CO<jats:sub>2<\/jats:sub>) gas mixture. A total of 14 healthy volunteers completed three resting state functional MRI (RS\u2010fMRI) scans, the first and third under normocapnia and the second under hypercapnia. VMHC measures were calculated as the correlation between the BOLD signal of each voxel and its counterpart in the opposite hemisphere. Group analysis was performed between the hypercapnic and normocapnic VMHC maps. VMHC showed a diffused decrease in response to hypercapnia. Significant regional decreases in VMHC were observed in all anatomical lobes, except for the occipital lobe, in the following functional hierarchical subdivisions: the primary sensory\u2010motor, unimodal, heteromodal, paralimbic, as well as in the following functional networks: ventral attention, somatomotor, default frontoparietal, and dorsal attention. Our observation that brain homotopy in RS\u2010fMRI is affected by arterial CO<jats:sub>2<\/jats:sub> levels suggests that caution should be used when comparing RS\u2010fMRI data between healthy controls and patients with pulmonary diseases and unusual respiratory patterns such as sleep apnea or chronic obstructive pulmonary disease. <jats:italic>Hum Brain Mapp 36:3912\u20133921, 2015<\/jats:italic>. \u00a9 <jats:bold>2015 Wiley Periodicals, Inc.<\/jats:bold><\/jats:p>","DOI":"10.1002\/hbm.22886","type":"journal-article","created":{"date-parts":[[2015,7,2]],"date-time":"2015-07-02T13:09:57Z","timestamp":1435842597000},"page":"3912-3921","source":"Crossref","is-referenced-by-count":23,"title":["The influence of mild carbon dioxide on brain functional homotopy using resting\u2010state fMRI"],"prefix":"10.1002","volume":"36","author":[{"given":"Olga","family":"Marshall","sequence":"first","affiliation":[{"name":"Radiology\/Center for Biomedical Imaging New York University School of 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