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Understanding this process is crucial for developing neurotherapeutic strategies for brain injury recovery. Neuroplasticity may be adaptive or maladaptive and is tightly linked with brain development and skill learning. Positron emission tomography (PET) is a molecular imaging technique that enables the analysis of neurochemical processes, including neurotransmitter function. Synaptic plasticity is fundamental for brain rewiring, and PET may be pivotal in assessing this process at the molecular level, though its relevance remains underestimated. Most brain plasticity studies rely on indirect measures like gray matter (GM) thickness. Studies employing PET have the potential to provide direct correlates of neuroplasticity at a molecular level, thus, contributing to a deeper understanding of brain reorganization. This systematic review provides a comprehensive overview of evidence for neuroplasticity in healthy and diseased human brains, focusing on PET studies. This approach offers an innovative perspective on the underlying neurobiological mechanisms in various clinical contexts. This review includes 15 studies: nine provide direct quantitative molecular evidence for plasticity, while others suggest potential adaptive responses. The findings highlight the need for clearer conceptual clarity regarding the definite existence of plasticity. Some studies do not definitively commit to the presence or absence of plasticity, allowing alternative interpretations. Nevertheless, the studies suggest that molecular quantification of synaptic status is a promising approach to studying neuroplasticity. It emphasizes the need for more objective and direct criteria in plasticity studies. Understanding this dynamic phenomenon is essential to enhance rehabilitation processes and postinjury clinical outcomes.<\/jats:p>","DOI":"10.1155\/np\/9423232","type":"journal-article","created":{"date-parts":[[2025,7,19]],"date-time":"2025-07-19T06:49:07Z","timestamp":1752907747000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Evidence for Neuroplasticity in the Human Brain in Health and Disease: A Systematic Review Focusing on Molecular Imaging Using PET"],"prefix":"10.1155","volume":"2025","author":[{"given":"Ferreira","family":"M.","sequence":"first","affiliation":[]},{"given":"Matias","family":"F.","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4145-854X","authenticated-orcid":false,"given":"Abrunhosa","family":"A.","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7184-185X","authenticated-orcid":false,"given":"Martins","family":"R.","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4364-6373","authenticated-orcid":false,"given":"Castelo-Branco","family":"M.","sequence":"additional","affiliation":[]}],"member":"311","published-online":{"date-parts":[[2025,7,18]]},"reference":[{"key":"e_1_2_9_1_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0742-08.2008"},{"key":"e_1_2_9_2_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-981-19-0209-3_1"},{"key":"e_1_2_9_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41380-022-01931-x"},{"key":"e_1_2_9_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neubiorev.2013.04.005"},{"key":"e_1_2_9_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41380-022-01520-y"},{"key":"e_1_2_9_6_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.neuro.27.070203.144216"},{"key":"e_1_2_9_7_2","first-page":"599","volume-title":"Handbook of Clinical Neurology","author":"Johnson B. 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