FMRI studies investigating the acquisition of sequential motor skills in 13 humans have revealed learning-related functional reorganizations of the cortico-striatal 14 and cortico-cerebellar motor systems in link with the hippocampus. Yet, the functional 15 significance of these activity level changes is not fully understood as they convey the 16 evolution of both sequence-specific knowledge and unspecific task expertise. Moreover, 17 these changes do not specifically assess the occurrence of learning-related plasticity. To 18 address these issues, we investigated local circuits tuning to sequence-specific 19 information using multivariate distances between patterns evoked by consolidated or 20 newly acquired motor sequences production. Results reveal that representations in 21 dorsolateral striatum, prefrontal and secondary motor cortices are greater when 22 executing consolidated sequences than untrained ones. By contrast, sequence 23 representations in the hippocampus and dorsomedial striatum are less engaged. Our 24 findings show, for the first time in humans, that complementary sequence-specific motor 25 representations evolve distinctively during critical phases of skill acquisition and 26 consolidation. 27 28 29Animals and humans are able to acquire and automatize new sequences of movements, 30 hence allowing them to expand and update their repertoire of complex goal-oriented 31 motor actions for long-term use. To investigate the mechanisms underlying this type 32 of procedural memory in humans, a large body of behavioral studies has used motor 33 sequence learning (MSL) tasks designed to test the ability to perform temporally ordered 34 and coordinated movements, learned either implicitly or explicitly and has assessed their 35 1 of 28 Manuscript submitted to eLife performances in different phases of the acquisition process (Korman et al. 2003; Abra-36 hamse et al. 2013; Diedrichsen and Kornysheva 2015; Verwey et al. 2015). While practice 37 of an explicit MSL task leads to substantial within-session execution improvements, there 38 is now ample evidence indicating that between-session maintenance, and even increases, 39 in performance can be observed after a night of sleep (Nettersheim et al. 2015; Landry et 40 al. 2016), while performance are unstable and tends to decay during an equal period of 41 wake (Doyon et al. 2009b; Brawn et al. 2010; Nettersheim et al. 2015; Landry et al. 2016). 42 Therefore, it is thought that sleep favors reprocessing of the motor memory trace, thus 43 promoting its consolidation for long-term skill proficiency (Fischer et al. 2002; see King et 44 al. 2017; Doyon et al. 2018 for recent in-depth reviews). 45 Functional magnetic resonance imaging (fMRI) studies using General-Linear-Model (GLM) 46 contrasts of activation have also revealed that MSL is associated with the recruitment of an 47 48 et al. 2015), whose contributions differentiate as learning progresses (Karni et al. 1998; 49 Dayan and Cohen 2011; Doyon et al. 2018). In f...
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