1 Department of Neurology, Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Germany. annatheklajaeger@gmail.com.
2 Center for Stroke Research Berlin (CSB), Charité-Universitätsmedizin Berlin, Berlin, Germany. annatheklajaeger@gmail.com.
3 Neuroscience Programme, Champalimaud Research, Lisbon, Portugal.
4 Department of Physics/Perform Center, Concordia University, Montreal, QC, Canada.
5 Montreal Heart Institute, Montreal, QC, Canada.
6 Department of Neurology, Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Germany.
7 Clinic of Neurology, Technical University Munich, Munich, Germany.
8 Department of Biomedical Engineering, McGill University, Montreal, QC, Canada.
9 Montreal Neurological Institute, Montreal, QC, Canada.
10 Center for Stroke Research Berlin (CSB), Charité-Un

In motor learning, sequence specificity, i.e. the learning of specific sequential associations, has predominantly been studied using task-based fMRI paradigms. However, offline changes in resting state functional connectivity after sequence-specific motor learning are less well understood. Previous research has established that plastic changes following motor learning can be divided into stages including fast learning, slow learning and retention. A description of how resting state functional connectivity after sequence-specific motor sequence learning (MSL) develops across these stages is missing. This study aimed to identify plastic alterations in whole-brain functional connectivity after learning a complex motor sequence by contrasting an active group who learned a complex sequence with a control group who performed a control task matched for motor execution. Resting state fMRI and behavioural performance were collected in both groups over the course of 5 consecutive training days and at follow-up after 12 days to encompass fast learning, slow learning, overall learning and retention. Between-group interaction analyses showed sequence-specific decreases in functional connectivity during overall learning in the right supplementary motor area (SMA). We found that connectivity changes in a key region of the motor network, the superior parietal cortex (SPC) were not a result of sequence-specific learning but were instead linked to motor execution. Our study confirms the sequence-specific role of SMA that has previously been identified in online task-based learning studies, and extends it to resting state network changes after sequence-specific MSL.