Aim To investigate whether plastic changes in brain structure and function assessed with MRI following training of a motor task agree with the predictions of the exploration-selection-refinement model (Makino et al. 2016; Lindenberger and Lövdén 2019). Background Understanding the process of skill acquisition, such as learning to play a musical instrument, is a long-standing topic in psychology and cognitive neuroscience. Building on theoretical work (Edelman 1987; Changeux 1989; Kilgard 2012; Dhawale et al. 2017), evidence from animal models (Molina-Luna et al. 2008; Xu et al. 2009; Yang et al. 2009; Reed et al. 2011; Makino et al. 2016), and our own work using repeated imaging of the human brain’s gray matter structure during motor learning (Wenger et al. 2016a), we have in recent years developed a model of the neural process of human skill acquisition (Wenger et al. 2017; Lindenberger and Lövdén 2019). According to this model, during learning the brain initially tries out numerous candidate circuits (exploration). Based on reinforcement, the best candidate circuit is then chosen (selection) for further local fine-tuning (refinement). During the exploration phase, this process is hypothesized to be associated with the growth of regional brain structure (expansion), which partially retracts (renormalization) after the best circuit for the task has been selected. The main purpose of the project is to empirically test an ensemble of predictions from this model. The microstructural alterations underlying plastic changes are possibly diverse, including dendritic branching and synaptogenesis, axon sprouting and glial changes (Zatorre et al. 2012). In particular, it is now well established that myelination is under the influence of neural activity (Ullén 2009; Fields 2015; Jensen and Yong 2016), and recent investigations have shown that production of new oligodendrocytes is necessary for optimal motor learning (Mckenzie et al. 2014; Xiao et al. 2016) and a requirement for memory consolidation in general (Fields and Bukalo 2020). Work linking myelination and cortical thickness assessed with MRI (Natu et al. 2018) opens the possibility that experience-dependent morphometric alterations seen in longitudinal studies (Draganski et al. 2004, 2006; Scholz et al. 2009; Engvig et al. 2010; Lövdén et al. 2010; Mårtensson et al. 2012; Kühn et al. 2014; Wenger et al. 2016b; de Lange et al. 2017) respond to myelin reorganization in the cortex. In the present study, we randomly allocated 70 healthy, right-handed younger adults (20-30 y. o.) to 2 groups of equal size. Subjects in the first group trained a motor task, consisting of typing predefined sequences of key combinations with the fingers of their left-hand on a keyboard, akin to playing short piano chord sequences. Over a period of 6 weeks, they practiced at home 5 days a week for about 20 minutes on a laptop that was provided. The second group did not practice the task, and subjects in both groups were scanned with MRI once a week. Subjects with previous experience in similar motor tasks (e.g. playing an instrument) were not included in the experiment. The data for this study have already been acquired and partially preprocessed. We have used a collection of MRI measurements to characterize the structural and functional changes triggered by the practice of the task. From MP2RAGE (Marques et al. 2010) and T2-w scans, we have derived cortical thickness (CT), gray matter volumes (GMV), and approximate T1 relaxation time values, which have been shown to have good sensitivity for myelin (Sereno et al. 2013). We will compare alterations over time in these measures in areas related to the execution of the motor task between the 2 groups. Based on our model of skill acquisition, we predict a pattern of expansion followed by renormalization of the structural measures in the group undergoing motor practice, whereas these measures will remain stable in the group not practicing the motor skill. REFERENCES Changeux J-P. 1989. Neuronal models of cognitive functions. Cognition. 33:63–109. de Lange AMG, Bråthen ACS, Rohani DA, Grydeland H, Fjell AM, Walhovd KB. 2017. The effects of memory training on behavioral and microstructural plasticity in young and older adults. Hum Brain Mapp. 38:5666–5680. Dhawale AK, Smith MA, Ölveczky BP. 2017. 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