, 2010) have suggested that pre-SMA mediates an inhibitory

effect of IFG over the primary motor cortex. In our view, NMA data buy Obeticholic Acid may be pertinent to such questions. We present data from the key NMA studies in a way that highlights their relevance to inhibitory cognitive control. We first consider the general method for identifying NMAs. Then we analyze the specificity for inhibiting different effector systems (speech, manual action etc). Then, we consider NMA localization and the features of the stimulation threshold required to elicit a negative motor response. We next consider subjective experience generated by NMA stimulation. Finally, the discussion section considers how NMA data may constrain cognitive and neurophysiological accounts of cognitive control. An introductory word of caution is important here. Effects of DES are typically more focal than those of non-invasive brain stimulation methods, such as TMS or transcranial INCB024360 mw direct current stimulation (tDCS).

The spatial resolution of DES is typically .5 cm (Mandonnet et al., 2009). TDCS has a typical current spread of the order of 2 cm (but it varies with different electrode parameters, see Faria et al., 2011), while TMS has a typical spatial resolution 1–2 cm, though this value is possibly improved for primary motor cortex mapping (Foltys et al., 2001). Nevertheless, although DES may be more local, it still targets a large and heterogeneous cluster of neurons, and a larger set of axons. The effects of DES may be mediated by stimulation or inhibition of neurons, including neurons relatively distant from the electrode site. In fact, remote effects STK38 of DES can be explained by active synaptic activation, rather than by passive current spread. Therefore, care is needed drawing conclusions about function of a stimulated area from DES results. Accordingly, we emphasise here that convergent evidence from other methods is particularly important in understanding the functional significance of NMAs. It is beyond the scope of this review to describe the possible and complex physiological effects of DES (see Borchers et al., 2012 for a critical review). A pioneering

NMA study is that of Lüders et al. (1987), who studied 42 patients. They stimulated each of a set of subdural electrodes with progressively increasing current. When an electrode did not produce any positive motor signs, it was next tested for negative motor responses. Patients were asked to perform rapid alternating eye, tongue, hand or foot movements. NMAs were defined as areas that when stimulated produced cessation/arrest or decrease of the ongoing voluntary movement, without loss of consciousness. Cases in which movement arrest is a secondary consequence of otherwise positive effects, such as muscular co-contraction, were excluded from the NMA definition. Twenty-four studies reporting NMAs were identified in the literature and form the basis of this review. They are summarised in Table 1.