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Basically, LTP-like plasticity is induced when anodal tDCS (a-tDCS) is applied over the primary motor cortex. However, it has been shown that specific parameters of a-tDCS can induce a plasticity reversal. We aimed to systematically assess the intensity threshold for reversal of the direction of plasticity induced by a-tDCS, monitored by corticospinal excitability (CSE), and explored mechanisms regulating this reversal. Fifteen healthy participants received a-tDCS in pseudo-random order for 26\u00a0min with four intensities of 0.3, 0.7, 1, and 1.5\u00a0mA. To measure CSE changes, single-pulse TMS was applied over the left M1, and motor evoked potentials of a contralateral hand muscle were recorded prior to a-tDCS, immediately and 30-min post-intervention. Paired-pulse TMS was used to evaluate intracortical excitation and inhibition. CSE increased significantly following a-tDCS with an intensity of 0.7\u00a0mA; however, the expected effect decreased and even reversed at intensities of 1 and 1.5\u00a0mA. ICF was significantly increased while SICI and LICI decreased at 0.7\u00a0mA. On the other hand, a significant decrease of ICF, but SICI and LICI enhancement was observed at intensities of 1, and 1.5\u00a0mA. The present findings show an intensity threshold of\u2009\u2265\u20091\u00a0mA for 26\u00a0min a-tDCS to reverse LTP- into LTD-like plasticity. It is suggested that increasing stimulation intensity, with constant stimulation duration, activates counter-regulatory mechanisms to prevent excessive brain excitation. Therefore, stimulation intensity and plasticity induced by a-tDCS might non-linearly correlate in scenarios with prolonged stimulation duration.<\/jats:p>","DOI":"10.1038\/s41598-020-72909-4","type":"journal-article","created":{"date-parts":[[2020,9,30]],"date-time":"2020-09-30T10:05:26Z","timestamp":1601460326000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":46,"title":["Determination of anodal tDCS intensity threshold for reversal of corticospinal excitability: an investigation for induction of counter-regulatory mechanisms"],"prefix":"10.1038","volume":"10","author":[{"given":"Maryam","family":"Hassanzahraee","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael A.","family":"Nitsche","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maryam","family":"Zoghi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shapour","family":"Jaberzadeh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,9,30]]},"reference":[{"key":"72909_CR1","doi-asserted-by":"crossref","first-page":"1899","DOI":"10.1212\/WNL.57.10.1899","volume":"57","author":"MA Nitsche","year":"2001","unstructured":"Nitsche, M. 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