Cocaine misuse leads to structural and functional changes in the brain (Ide et al., 2016; Ide et al., 2013) and can be considered a chronic mental disorder (Volkow et al., 2016). As with other substance use disorders, cocaine misuse involves multiple etiological processes, including deficient behavioral control (Garavan and Hester, 2007; Lundqvist, 2010; Sim et al., 2007), likely as a result of the chronic effects of cocaine on the brain. In animal studies, rats chronically exposed to cocaine showed significantly less neuronal activity in the prefrontal cortex (PFC), a critical brain region that supports behavioral control (Kane et al., 2020; Pastor et al., 2021). Studies have employed magnetic resonance imaging (MRI) to reveal altered regional brain activation during various behavioral challenges in chronic cocaine users and individuals who have been prenatally exposed to cocaine (Crunelle et al., 2012; Garavan and Hester, 2007; Roussotte and Soderberg, 2010). These studies also implicated the PFC, including the anterior cingulate cortex and dorsolateral PFC, in decision-making deficits in association with cocaine misuse (Hester et al., 2013; Hester and Garavan, 2005; Lundqvist, 2010). Other studies reported changes in the functional connectivity of the PFC and subcortical structures during cognitive control in cocaine users (Cisler et al., 2013; Zhang et al., 2014).

Response inhibition represents a critical component of executive control (Clark, 1996; van der Molen, 2000). Response inhibition involves the suppression of responses that are no longer needed or are inappropriate and allows one to respond flexibly to changing circumstances. Neuroimaging studies have provided ample evidence for the role of the PFC in inhibitory control (Jones and Graff-Radford, 2021). One of the most widely used laboratory paradigms to study response inhibition is the stop-signal task (SST), where participants are tested for the efficiency in terminating an unwanted action (Duann et al., 2009; Li et al., 2008; Manza et al., 2016; Verbruggen and Logan, 2008b; Winkler et al., 2012; Zhang et al., 2015). The PFC, including the medial PFC, inferior frontal gyrus, and basal ganglia are involved in the inhibitory process during the SST (Li, 2015).

A number of studies have used the SST to investigate functional brain changes in cocaine misuse. With independent component analyses (ICA) of the fMRI time series collected of the SST, Elton and colleagues demonstrated changes in network activities in relation to inhibitory motor control in cocaine users relative to controls (Elton et al., 2012). Zhang et al. reported in cocaine dependent individuals altered dynamic network connectivities during the SST (Zhang et al., 2018). With a monetary incentive stop task to investigate the moderating effects of rewards on proactive control, Nigam and colleagues showed diminished proactive control in cocaine-dependent individuals, as compared to non-drug using controls (Nigam et al., 2020). Bayesian modeling of SST performance showed that individuals with cocaine dependence were less engaged in using contextual information for behavioral adjustment (Ide et al., 2015). With a variant SST involving stimuli of drug and food words, cocaine-dependent vs. control participants demonstrated diminished dorsolateral PFC responses to drug vs. food words during successful inhibitions (Ceceli et al., 2022). Others employed spatial ICA and showed “circuit failure” in connection with impairment of response inhibition in cocaine misuse (Wang et al., 2018) or distinguished individuals of cocaine misuse from healthy controls based on voxel-wise thalamic connectivities to the independent components of regional activities identified from the SST (Zhang et al., 2016).

Thus, a substantial body of literature has provided evidence of cognitive control deficits and demonstrated the neural markers of the deficits in cocaine misuse. However, it remains unclear how cognitive control deficits may vary across cocaine users with respect to the chronicity and severity of cocaine use or whether the deficits ameliorate during the course of abstinence. To investigate these issues, we hypothesized that cognitive control dysfunction, as reflected in prolonged stop-signal reaction time in the SSRT, would be more severe in individuals with longer duration of cocaine use. In contrast, cognitive dysfunction would become less severe along with longer duration of abstinence. By combining the SST with functional brain imaging, we would also investigate the neural processes of cognitive control in association with the duration of use and duration of abstinence in chronic cocaine users.