Early onset consumption of coca paste associated with executive-attention vulnerability markers linked to caudate-frontal structural and functional abnormalities.

Coca paste is the most popular form of smoked cocaine (SC) in Latin America and also the most widespread among adolescents in vulnerable sectors of society, thus representing a significant public health concern. Despite evidence suggesting that abnormal executive-attention function is predictive of addiction to stimulant drugs, no study to date has compared clinically relevant neuropsychological (NPS) and physiological variables between individuals with histories of smoked cocaine dependence (SCD) and insufflated cocaine hydrochloride dependence (ICD). In this study we evaluated 25 SCD and 22 ICD subjects matched by poly-consumption profiles, and 25 healthy controls (CTR) matched by age, gender, education, and socioeconomic status. An exhaustive NPS battery was used to assess cognitive domains (attention, executive functions, fluid intelligence, memory, language and social cognition). We complemented this assessment with structural (MRI) and functional (fMRI) neuroimaging data. We found that executive function and attention impairments could be explained by the administration route of cocaine, with strongest impairments for the SCD group. SCD also presented reduced grey matter density relative to ICD and CTR in the bilateral caudate, a key area for executive and attentional function. Functional connectivity between left caudate and inferior frontal regions mediated the association between brain structure and behavioral performance. Our results highlight the relevance of assessing the route of administration of stimulants, both in clinical and research settings.

Multimodal neurocognitive markers of interoceptive tuning in smoked cocaine.

Contemporary neurocognitive models of drug addiction have associated this condition with changes in interoception -namely, the sensing and processing of body signals that fulfill homeostatic functions relevant for the onset and maintenance of addictive behavior. However, most previous evidence is inconsistent, behaviorally unspecific, and virtually null in terms of direct electrophysiological and multimodal markers. To circumvent these limitations, we conducted the first assessment of the relation between cardiac interoception and smoked cocaine dependence (SCD) in a sample of (a) 25 participants who fulfilled criteria for dependence on such a drug, (b) 22 participants addicted to insufflated clorhidrate cocaine (only for behavioral assessment), and (c) 25 healthy controls matched by age, gender, education, and socioeconomic status. We use a validated heartbeat-detection (HBD) task and measured modulations of the heart-evoked potential (HEP) during interoceptive accuracy and interoceptive learning conditions. We complemented this behavioral and electrophysiological data with offline structural (MRI) and functional connectivity (fMRI) analysis of the main interoceptive hubs. HBD and HEP results convergently showed that SCD subjects presented ongoing psychophysiological measures of enhanced interoceptive accuracy. This pattern was associated with a structural and functional tuning of interoceptive networks (reduced volume and specialized network segregation). Taken together, our findings provide the first evidence of an association between cardiac interoception and smoked cocaine, partially supporting models that propose hyper-interoception as a key aspect of addiction. More generally, our study shows that multimodal assessments of interoception could substantially inform the clinical and neurocognitive characterization of psychophysiological and neurocognitive adaptations triggered by addiction.