The processing of external salient stimuli (i.e., exteroceptive processing) is critical for responding and adapting to the environment. The posterior cingulate cortex (PCC) and precuneus have been implicated in exteroceptive processing (Fransson, 2005; Lou et al., 2010; Luber et al., 2012) and exhibit activation that is correlated with the default mode network (Fox et al., 2005; Raichle, 2011; Utevsky et al., 2014). This correlation with the default mode network, a network of brain regions that exhibits activation during resting state and deactivation when engaged in a task, is thought to be critical for continuously monitoring the environment for self‐relevant stimuli. This constant monitoring is imperative to quickly identify and react to relevant external stimuli (e.g., predators) and thus, is likely a readily available attentional resource (Gusnard & Raichle, 2001; Raichle et al., 2001; Corbetta et al., 2008; Uddin, 2015). Determining the external stimulus’ relevance to the self is also critical in selecting the appropriate response and has been reported to be driven by the PCC (Schilbach et al., 2008; Davey et al., 2016).

Exteroception is of particular importance in substance abuse as increased awareness to drug‐related cues may underlie increased craving and lead to drug‐seeking behavior (Siegel, 2005; Littel et al., 2012; Paulus et al., 2013; Cadet et al., 2014; DeWitt et al., 2015). In substance abuse, neuroimaging studies indicate greater activity in the PCC and precuneus with drug‐cue exposure in cocaine (Grant et al., 1996), alcohol (Tapert et al., 2003), nicotine (McBride et al., 2006; Brody et al., 2007; McClernon et al., 2009; Claus et al., 2013), and cannabis (Feldstein Ewing et al., 2012; Filbey & Dunlop, 2014; Filbey et al., 2016) users. Specifically in cannabis users, greater activation in the PCC and precuneus in response to cannabis cues indicates a hyper‐sensitization to these cues (Filbey et al., 2016) and has also been associated with decreased performance on the Iowa Gambling Task that assesses strategic decision‐making (Bolla et al., 2005; Wesley et al., 2011). Together with studies reporting increased cue‐elicited craving in cannabis users (Wölfling et al., 2008; Filbey et al., 2009; Filbey & DeWitt, 2012), these findings suggest that cannabis users not only have increased salience to cannabis cues and cue‐elicited craving, but also compromised decision‐making that may lead to subsequent drug‐seeking behavior.

The link between processing of external self‐relevant stimuli and increased salience to cannabis cues that is purportedly driven by the PCC and precuneus provides an interesting approach to potentially modulate craving via manipulation of these regions in cannabis users. A method for manipulation of these regions is through repetitive transcranial magnetic stimulation (rTMS). rTMS induces neuroplastic changes through the application of magnetic stimuli (produced in a coil of wire called the magnetic coil) directly to a brain area and can modulate cortical excitability using either inhibitory low frequency (≤ 1 Hz; LF) or excitatory high frequency (≥ 5 Hz; HF) stimulation. This non‐invasive neuromodulation technique has been applied to relieve symptoms for neurological and psychiatric disorders (McNamara et al., 2001; Lomarev et al., 2006; Poulet et al., 2010) and to reduce craving in nicotine (Amiaz et al., 2009; Hayashi et al., 2013; Li et al., 2013; Pripfl et al., 2014), cocaine (Camprodon et al., 2007; Politi et al., 2008), and alcohol users (Mishra et al., 2010; De Ridder et al., 2011; Rapinesi et al., 2013). In cannabis users, the literature has been limited with only two studies examining the effects of rTMS. Fitzgerald and colleagues indicated a reduction in cortical inhibition after single and paired rTMS targeting the motor cortex in cannabis users in comparison to control participants (Fitzgerald et al., 2009). Sahlem and colleagues reported no change in craving after a single session of 10 Hz rTMS to the left dorsolateral prefrontal cortex (Sahlem et al., 2018). While these studies have largely focused on applying rTMS using a figure‐eight coil to the dorsolateral prefrontal cortex (Bellamoli et al., 2014; Gorelick et al., 2014; Salling & Martinez, 2016), the above evidence suggests that the PCC and precuneus may also be appropriate targets for applying rTMS to modulate response to self‐relevant stimuli and reduce craving. Targeting deeper brain areas, such as the PCC, have shown to be possible using more advanced rTMS coil designs than the figure‐8 coil (Deng et al., 2013, 2014); however, only few rTMS studies have investigated the PCC using this double‐cone coil (Hayward et al., 2007; Vanneste et al., 2012).

Thus, the aim of this study was to modulate response to external self‐relevant stimuli using double‐cone coil rTMS by targeting the PCC and precuneus and to investigate the role of these regions in processing salient stimuli in cannabis users and non‐using controls. To assess neural response to external self‐relevant stimuli, we modified the oddball paradigm to include self‐relevant and cannabis‐related stimuli that occurred infrequently and were expected to elicit the P3 response (Gray et al., 2004) as well as the preceding P2 and N2 responses measured through electroencephalography (EEG). We hypothesized a greater P2, N2, and P3 response to self‐relevant stimuli during baseline compared to after HF rTMS (i.e., 10 Hz) in both cannabis users and non‐using controls and no change after LF rTMS (i.e., 1 Hz) as this condition was used as a comparison measure. We also predicted a greater response to cannabis‐related stimuli during baseline compared to after HF rTMS in cannabis users due to the high salience of these cues to users, but not in controls.