The net result would be akin to the phenomena of surround inhibition reported in the motor cortex that enhances motor ability (Hallett, 2004; Beck & Hallett, 2010), the visual cortex that enhances visual perception (Angelucci et al., 2002) and the somatosensory cortex that enhances tactile acuity (Drevets et al., 1995). State dependency would also explain the lack Z-VAD-FMK datasheet of effect elicited by 5 Hz rTMS where both the sequence-related and non-sequence-related neural activity would be facilitated. However, given the already elevated excitability in the neurons involved with the repeated sequence representation, the effects of the rTMS would be more

pronounced in the less active neural pathways representing the random sequence compared with the already excited neural pathways representing the repeated sequence (Bienenstock et al., 1982; Kuo et al., 2008). The net result would be a reduction in the difference between the signal (repeated sequence neural activity) and the noise (random sequence neural activity). One limitation to the current work is that we are unable to directly assess changes in cortical excitability of the PMd itself. Future work is needed to determine whether rTMS following practice of interleaved random and repeated

sequences can elicit state dependency during the period of early offline consolidation. Our data highlight the potential differential roles for the PMd in implicit p38 MAPK activation motor learning and early offline motor memory consolidation of a novel motor task. The results confirm past work demonstrating that with practice participants can

implicitly learn a repeated sequence (Brashers-Krug et al., 1996; Shadmehr & Holcomb, 1997; Meehan et al., 2011) and that sequence-specific learning can be altered via rTMS (Boyd & Linsdell, 2009). Importantly, we found that 1 Hz rTMS over the PMd during early consolidation improved sequence-specific implicit motor learning, probably by reducing competition between consolidation of motor parameters and action selection following interleaved practice. Applying rTMS during early consolidation O-methylated flavonoid may be an adjunctive mechanism to enhance gains associated with practice through consolidation of specific elements of motor memory. Support was provided to S.K.M. by the Canadian Institutes of Health Research and the Michael Smith Foundation for Health Research and to L.A.B. by the Canada Research Chairs and the Michael Smith Foundation for Health Research. This work was also supported by awards from the Natural Sciences and Engineering Research Council of Canada (Award #401890) and the Vancouver Coastal Health Research Institute to L.A.B.