, 2004 and Rushworth et al., 2002), as volition or self-generated actions (not externally cued) appear to be a common factor across experimental findings. For example, the Bereitschaftspotential – a negative premotor potential recorded over central frontal electrodes in humans – has larger peak amplitudes with self-initiated actions ( Deecke & Kornhuber, 1978); while in monkeys, lesions of the pre-SMA impair the ability to initiate arbitrary movements to obtain a reward, but the effect is ameliorated if the animals

Selumetinib are cued with an external tone ( Thaler, Chen, Nixon, Stern, & Passingham, 1995). Unilateral inactivation of monkey pre-SMA with muscimol has been found to induce deficits in sequence learning, but performance of previously well-learnt sequences was left intact (Nakamura, Sakai, & Hikosaka, 1999). This has

led to the suggestion that this might reflect an impairment of the mechanism responsible for updating the association between the correct action given current conditions. Therefore, it is possible that deficits in self-initiated action observed after SMA/pre-SMA disruption might arise from a failure to make the appropriate connection between the action to be initiated in a novel situation ( Nachev et al., 2008). Trans-cranial magnetic stimulation (TMS) has also been employed to measure physiological interactions between pre-SMA Cyclopamine solubility dmso and other brain regions associated with response selection. This has demonstrated that in the presence

of response conflict, pre-SMA facilitates motor-evoked potentials in M1 during action reprogramming (Mars et al., 2009), and suppresses unselected response options (Duque, Olivier, & Rushworth, 2013). TMS over pre-SMA has been associated with an increased delay in the ability to inhibit responses (Cai, George, Verbruggen, Chambers, & Aron, 2012), but there is also evidence that activity in pre-SMA can occur before stopping is initiated, which would be indicative of a role in selecting rather than implementing responses (Swann et al., 2012). However, a caveat of this approach is that TMS stimulation which induces a transient ‘lesion’ may also propagate Fludarabine in vitro to other brain networks. Similar effects on network function have also been observed following anatomical focal lesions, dependent on the position of the brain area within the network architecture and degree of white matter involvement (Gratton, Nomura, Pérez, & D’Esposito, 2012). Although cognitive control, self-initiated action and sequence learning may not be mutually exclusive functions, providing an overarching framework which can account for the range of such complex behaviour has proven difficult. Due to the extremely rare incidence of focal damage to this brain area in humans, only a very small number of lesion studies of pre-SMA have been reported.