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These phenotypes may be associated with different pathophysiological mechanisms produced by a cortical-subcortical network involving even non-dopaminergic areas traditionally not directly related to PD. In this study, we propose a bio-constrained computational model to study the neural mechanisms underlying a possible type of PD tremor: the one mainly involving the serotoninergic system. The simulations run with the model demonstrate that a physiological serotonin increase can partially recover dopamine levels at the early stages of the disease before the manifestation of overt tremor. This result suggests that monitoring serotonin concentration changes could be critical for early diagnosis. The simulations also show the effectiveness of a new pharmacological treatment for tremor that acts on serotonin to recover dopamine levels. This latter result has been validated by reproducing existing data collected with human patients.<\/jats:p>","DOI":"10.3389\/fnsys.2021.682990","type":"journal-article","created":{"date-parts":[[2021,7,20]],"date-time":"2021-07-20T12:22:07Z","timestamp":1626783727000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":12,"title":["Increasing Serotonin to Reduce Parkinsonian Tremor"],"prefix":"10.3389","volume":"15","author":[{"given":"Daniele","family":"Caligiore","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesco","family":"Montedori","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Silvia","family":"Buscaglione","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adriano","family":"Capirchio","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2021,7,20]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"357","DOI":"10.1146\/annurev.ne.09.030186.002041","article-title":"Parallel organization of functionally segregated circuits linking basal ganglia and cortex","volume":"9","author":"Alexander","year":"1986","journal-title":"Ann. 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