, 2009). The involvement of the striatum

in the stages in which motor skills become automatic has been confirmed in human neuroimaging studies (Ashby et al., 2010, Lehéricy et al., 2005 and Poldrack et al., 2005). For example, using a dual-task design, in which a sequence of finger movements was learned while assessing the influence of a secondary interfering task, it was found that automaticity was accompanied by a decrease in activation in the associative striatum (Poldrack et al., 2005 and Lehéricy et al., 2005). Of note, the slow stage of motor skill learning in both humans and animals consistently engages M1, a key brain region in other stages of learning as well. Training to perform an explicit sequence of finger movements over several weeks showed progressively increasing BOLD activity in M1 (Karni et al., 1995, Karni et al., 1998, Floyer-Lea Lenvatinib mouse www.selleckchem.com/products/MLN-2238.html and Matthews, 2005 and Lehéricy et al., 2005; but see Xiong et al., 2009 and Ma et al., 2010), interpreted as reflecting recruitment of additional M1 units into the

local network that represents the acquired sequence of movements (Ungerleider et al., 2002). Learning a motor sequence over several days is also accompanied by an increase in the size of motor maps and corticomotoneuronal excitability of the digits involved in the task, both measured with TMS (Pascual-Leone et al., 1995). This particular reorganization within M1 is related to learning because simple repetition of movements in the absence of a sequential order did not induce such effect. Consistently, facilitatory stimulation of M1 over 5 days with anodal transcranial direct current stimulation (tDCS) improved learning of a sequential visuomotor task. Of note, the advantage in skill of the stimulated group also relative to the sham control group was still present 90 days later (Reis et al., 2009). These results support a causal link between M1 function and motor skill learning when training over multiple sessions. Plastic changes in M1 function linked with slow motor skill learning are well established in animal models as well. For example, reorganization

of movement representations in M1 has been documented in squirrel monkeys (Nudo et al., 1996) and rodents (Kleim et al., 1998 and Kleim et al., 2004). It was found that an expansion in movement representations with training, detectable only after substantial practice periods, paralleled behavioral gains (Kleim et al., 2004 and Monfils et al., 2005). The extent to which changes in motor maps in humans or animals have a causal link with slow learning remains to be more carefully studied (Monfils et al., 2005), but the finding discussed above that facilitatory stimulation of M1 improves learning is suggestive of such a link (Reis et al., 2009). In addition to reorganization of functional brain networks, slow learning is associated with structural plasticity in gray matter (for review, see Draganski and May, 2008 and May and Gaser, 2006).