Mikuni et al. (2006), on the other hand, reported four sites where stimulation initially elicited a negative response, but increasing stimulation generated a positive effect. The readiness potential (RP) is an Dasatinib clinical trial established neurophysiological signal classically recorded in the second or so preceding voluntary movements (Shibasaki and Hallett, 2006). RPs

are often recorded in subdural electrodes generating positive motor signs (Ikeda et al., 1995a, Ikeda et al., 1995b, Ikeda et al., 1992, Lee et al., 1986, Neshige et al., 1988, Rektor et al., 1994 and Sakamoto et al., 1991) and are generally interpreted as positive preparation of skilled movement. RPs were occasionally reported within NMAs, (Ikeda et al., 1993, Kunieda et al., 2004 and Yazawa et al., 2000). Ikeda reported RPs from one electrode, within the SMA, that qualified as an NMA on the basis of stimulation testing. This potential occurred in association with both ipsi- and contralateral single

or repetitive finger movements. Yazawa et al. also found RPs in two NMAs situated buy Seliciclib within the SMA. Again, these RPs were not strongly selective for specific movements. Finally, Kunieda found one NMA site that showed a RP preceding both foot and shoulder movement. Kunieda et al. report the existence of ‘omni-RPs’, i.e., RPs associated with several movement effectors. They further noted that these are often found in electrodes adjacent to NMAs. The existence of RPs in NMAs might appear incompatible with the concept PtdIns(3,4)P2 that NMAs have a role in inhibitory control of action. However, Yazawa et al. (1998) reported RPs from several electrodes (including both NMAs and electrodes eliciting positive responses) prior to stopping a voluntary muscle contraction, as well as contracting the muscle. Nonivasive recordings confirm this finding. Electroencephalographic (EEG) recordings before the

end of prolonged muscle contractions show RPs before muscle relaxation of both hand ( Terada et al., 1995) and foot ( Terada et al., 1999). Similarly, neuroimaging studies showed greater activations ( Toma et al., 1999) in SMA and pre-SMA before muscle relaxation than before muscle contraction. This suggests that the cortical outflow from areas such as SMA, premotor cortex and M1 may recruit inhibitory interneurons in the spinal cord to inhibit muscle activity ( Shibasaki and Hallett, 2006). In summary, the presence of RPs cannot, in itself, be taken as evidence against an inhibitory function of NMAs. Negative motor seizures are a rare epileptic condition that consists of solely motor arrest without loss of awareness (Lüders et al., 1998). If negative motor seizures originate in NMA, they may give important clues to the normal functions of NMA, since seizure activity often produces results consistent with the normal functional specialisation of the area where the seizure occurs. Recently, it has been suggested that NMAs are indeed responsible for negative motor seizures (Ikeda et al., 2009).