to midbrain DA neurons, terminating both within the SN proper as well as in the VTA. They arise from a broad region of the PFC, including the DLPfcx, cingulate, and orbital cortices. Indeed, these pyramidal neurons (Figure 1) could be exploited as the primary target of the TMS stimulus and their increased activity to produce, ultimately, an enhancement in DA availability in the synaptic cleft in the Nacc. Schematically, the hypothesized circuit (Figure 2) would be the following: TMS → DLPfcx → VTA → DA increase in forebrain projection site (i.e., Nacc). In this context, it is imperative to employ stimulation parameters consonant with the physiological activity of the system under study to restore pre-drug DA levels. For instance, it has been shown that DLPfcx stimulation produces bursts in rat DA neurons (Gariano and Groves, 1988; Murase et al., 1993), highlighting the importance of stimulation parameters. Indeed, burst firing is more efficacious than single spiking (of identical frequency but evenly spaced action potentials) in inducing DA release in terminal areas (Gonon, 1988; Manley et al., 1992). Consistently, the role of DLPfcx in regulating basal DA activity through the VTA has been reported (Taber et al., 1995; Karreman and Moghaddam, 1996).
