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.