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Recent evidence suggests that transcranial direct current stimulation (tDCS) can influence the activity of large-scale functional brain networks. We characterized brain-wide changes in functional network segregation (i.e. the balance of within vs. between-network connectivity strength) induced by high-definition (HD) tDCS in older adults with mild cognitive impairment (MCI) during virtual spatial navigation. Twenty patients with MCI and 22 cognitively intact older adults (healthy controls\u2014HC) underwent functional magnetic resonance imaging following two counterbalanced HD-tDCS sessions (one active, one sham) that targeted the right parietal cortex (center anode at P2) and delivered 2\u00a0mA for 20\u00a0min. Compared to HC, MCI patients showed lower brain-wide network segregation following sham HD-tDCS. However, following active HD-tDCS, MCI patients\u2019 network segregation increased to levels similar to those in HC, suggesting functional normalization. Follow-up analyses indicated that the increase in network segregation for MCI patients was driven by HD-tDCS effects on the \u201chigh-level\u201d\/association brain networks, in particular the dorsal-attention and default-mode networks. HD-tDCS over the right parietal cortex may normalize the segregation\/integration balance of association networks during spatial navigation in MCI patients, highlighting its potential to restore brain activity in Alzheimer\u2019s disease.<\/jats:p>","DOI":"10.1093\/cercor\/bhac010","type":"journal-article","created":{"date-parts":[[2022,1,12]],"date-time":"2022-01-12T04:22:02Z","timestamp":1641961322000},"page":"5230-5241","source":"Crossref","is-referenced-by-count":26,"title":["High-definition transcranial direct current stimulation enhances network segregation during spatial navigation in mild cognitive impairment"],"prefix":"10.1093","volume":"32","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1391-785X","authenticated-orcid":false,"given":"Alexandru D","family":"Iordan","sequence":"first","affiliation":[{"name":"Department of Psychology , , Ann Arbor, MI 48109 , USA"},{"name":"University of Michigan , , Ann Arbor, MI 48109 , USA"},{"name":"Research Program on Cognition and Neuromodulation Based Interventions , Department of Psychiatry, , Ann Arbor, MI 48105 , USA"},{"name":"University of Michigan , Department of Psychiatry, , Ann Arbor, MI 48105 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6144-5802","authenticated-orcid":false,"given":"Shannon","family":"Ryan","sequence":"additional","affiliation":[{"name":"Research Program on Cognition and Neuromodulation Based Interventions , Department of Psychiatry, , Ann Arbor, MI 48105 , USA"},{"name":"University of Michigan , Department of Psychiatry, , Ann Arbor, MI 48105 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6807-6106","authenticated-orcid":false,"given":"Troy","family":"Tyszkowski","sequence":"additional","affiliation":[{"name":"Research Program on Cognition and Neuromodulation Based Interventions , Department of Psychiatry, , Ann Arbor, MI 48105 , USA"},{"name":"University of Michigan , Department of Psychiatry, , Ann Arbor, MI 48105 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6690-9757","authenticated-orcid":false,"given":"Scott J","family":"Peltier","sequence":"additional","affiliation":[{"name":"Functional MRI Laboratory , , Ann Arbor, MI 48109 , USA"},{"name":"University of Michigan , , Ann Arbor, MI 48109 , USA"},{"name":"Department of Biomedical Engineering , , Ann Arbor, MI 48109 , USA"},{"name":"University of Michigan , , Ann Arbor, MI 48109 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6711-6356","authenticated-orcid":false,"given":"Annalise","family":"Rahman-Filipiak","sequence":"additional","affiliation":[{"name":"Research Program on Cognition and Neuromodulation Based Interventions , Department of Psychiatry, , Ann Arbor, MI 48105 , USA"},{"name":"University of Michigan , Department of Psychiatry, , Ann Arbor, MI 48105 , 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