Denial in methamphetamine users: Associations with cognition and functional connectivity in brain

Abstract

Background Despite harmful consequences of drug addiction, it is common for individuals with substance use disorders to deny having problems with drugs. Emerging evidence suggests that some drug users lack insight into their behavior due to neurocognitive dysfunction, but little research has examined potential neurocognitive contributions to denial. Methods This study explored the relationship between denial, cognitive performance and functional connectivity in brain. The participants were 58 non-treatment-seeking, methamphetamine-dependent participants who completed the URICA Precontemplation scale, a self-report measure of denial of drug problems warranting change, as well as a cognitive test battery. A subset of participants (N=21) had functional MRI scans assessing resting-state functional connectivity. Given literature indicating roles of the rostral anterior cingulate (rACC), anterior insula and precuneus in self-awareness, relationships between denial and resting-state connectivity were tested using seeds placed in these regions. Results The results revealed a negative relationship between denial and an overall cognitive battery score (p=0.001), the effect being driven particularly by performance on tests of memory and executive function. Denial was negatively associated with strength of connectivity between the rACC and regions of the frontal lobe (precentral gyri, left ventromedial prefrontal cortex, left orbitofrontal cortex), limbic system (left amygdala, left hippocampus and left parahippocampal gyrus), occipital lobes and cerebellum; and between the precuneus and the midbrain and cerebellum. Anterior insula connectivity was unrelated to denial. Conclusions These findings suggest that denial by methamphetamine users is linked with a cognitive and neural phenotype that may impede the development of insight into their behavior.

Metacognitive impairment in active cocaine use disorder is associated with individual differences in brain structure

“…In another study, orbitofrontal cortex lesions in rats produced impairment on a highly similar task that examined “confidence” in decision-making (i.e., the amount of time spent waiting for a reward following a correct choice) (Lak et al, 2014). For the latter (theory), a metacognitive deficit in basic perceptual functions in active CUD may parsimoniously accommodate and reveal mechanistic underpinnings of additional diverse findings in the literature, including deficient self-monitoring of task-related errors (Hester et al, 2007), reduced emotional awareness (Payer et al, 2011), ‘denial’ of illness severity (Dean et al, 2015), and underestimation of one’s drug-related self-control and cognitive-emotional deficits (Ersche et al, 2012; Verdejo-Garcia and Perez-Garcia, 2008). Moreover, the current results with a perceptual task have implications for research that emphasizes the importance of more basic sensory processes in understanding core pathophysiology of addiction (Yalachkov et al, 2010).…”

Increased self-reported impulsivity in methamphetamine users maintaining drug abstinence

“…Participants were initially recruited for studies of brain structure and cognition (e.g., 23, 24). Nine subjects participated in a previous study of methamphetamine withdrawal symptoms (22).…”

Medications for substance use disorders (SUD): emerging approaches

“…This may occur for a variety of practical, ethical and regulatory reasons [199]. It is unclear if the study of such “non-treatment seeking” participants results in challenges to appropriate “go/no-go” decisions for progression to further clinical development [18,199]. It is possible that the practice of studying non-treatment seekers may affect development of different types of pharmacotherapies in a different manner.…”