Fast learning of sequential motor tasks modulates regional brain activity in the dorsolateral prefrontal cortex (DLPFC), primary motor cortex (M1), and presupplementary motor area (preSMA) (Floyer-Lea and Matthews, 2005 and Sakai et al., 1999), which show decreased activation as learning progresses, and in the premotor cortex, supplementary motor area (SMA),

parietal regions, striatum, and the cerebellum, which show increased activation with learning (see Figure 3; Grafton et al., 2002, Honda et al., 1998 and Floyer-Lea and Matthews, 2005). Thus, learning is associated with differential regional modulation of blood oxygenation level-dependent (BOLD) activity or regional cerebral blood flow (rCBF). Increasing activation is thought to reflect recruitment Pexidartinib supplier of additional cortical substrates with practice (Poldrack, 2000). Decreasing activation, on the other hand, suggests that the task can be carried out using fewer neuronal resources as fast learning proceeds http://www.selleckchem.com/products/AZD2281(Olaparib).html (Poldrack, 2000). A valuable framework for interpreting the role of this complex pattern of recruitment has been proposed by Hikosaka and colleagues

(Hikosaka et al., 2002a) in a model describing the mechanisms for sequential motor skill learning. According to this model, two parallel loop circuits operate in learning spatial and motor features of sequences. Whereas learning spatial coordinates is supported by a frontoparietal-associative striatum-cerebellar circuit, learning motor coordinates is supported by an M1-sensorimotor striatum-cerebellar circuit. Transformations

between the two coordinate systems rely, according to this model, on the contribution of the SMA, pre-SMA, and premotor cortices. Importantly, it was argued that learning spatial coordinates is faster, yet requires additional attentional and executive resources, putatively provided by prefrontal PDK4 cortical regions (Miller and Cohen, 2001). Similarly, in another model, Doyon and Ungerleider (2002) proposed that during fast learning a cortico-striato-thalamo-cortical loop and a cortico-cerebello-thalamo-cortical loop are both recruited, operating in parallel. Further, interactions between the two systems were believed to be crucial for establishing the motor routines necessary for learning new motor skills (Doyon and Ungerleider, 2002 and Doyon and Benali, 2005). Both models share the view that motor skill learning involves interactions between distinct cortical and subcortical circuits, crucial for the unique cognitive and control demands associated with this stage of skill acquisition (Hikosaka et al., 2002a and Doyon and Ungerleider, 2002). One of the key brain regions involved in fast learning is M1. Fast motor skill learning is associated with substantial recruitment of neurons in M1 in behaving mice during the initial stages of learning an accelerating rotarod task (Costa et al.