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While the mechanism underlying load\u2010dependent regulations in cognitive functions has been extensively investigated, their influence on downstream execution in motor skill learning remains less understood. The current study extends the understanding of whether and how learning alters the load\u2010dependent activation pattern by a longitudinal functional near\u2010infrared spectroscopy (fNIRS) study in which 30 healthy participants (15 females) engaged in extensive practice on a two\u2010dimensional continuous hand tracking task with varying task difficulty. We proposed the index of difficulty (ID) as a quantitative measure of task difficulty, which was monotonically associated with a psychometric measure of subjective workload. As learning progressed, participants exhibited enhanced behavioral and metacognitive performance. Behavioral improvements were accompanied by plastic changes in the inferior prefrontal cortex, reflecting a shift in control strategy during motor learning. Most importantly, we found robust evidence of the learning\u2010induced alteration in load\u2010dependent cortical activation patterns, indicating that effective motor skill learning may lead to the emergence of an inverted\u2010U relationship between cortical activation and load level in the contralateral pre\u2010motor and supplementary motor areas. Our findings provide new insights into the learning\u2010induced plasticity in brain and behavior, highlighting the load\u2010dependent contributions in motor skill learning.<\/jats:p>","DOI":"10.1002\/hbm.70208","type":"journal-article","created":{"date-parts":[[2025,4,6]],"date-time":"2025-04-06T01:11:51Z","timestamp":1743901911000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Effective Motor Skill Learning Induces Inverted\u2010U Load\u2010Dependent Activation in Contralateral Pre\u2010Motor and Supplementary Motor Area"],"prefix":"10.1002","volume":"46","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7568-9226","authenticated-orcid":false,"given":"Xiaolu","family":"Wang","sequence":"first","affiliation":[{"name":"Key Laboratory of Sensing Technology and Biomedical Instrument of Guangdong Province, School of Biomedical Engineering Sun Yat\u2010Sen University  Shenzhen 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