Structural and functional signatures of executive deficits after early use of cocaine depend upon route of administration

Abstract

Background: There is growing evidence linking cocaine consumption with a broad spectrum of neurocognitive deficits. Despite of evidence suggesting that the route of administration should be taken into account to assess the short and long term effects of cocaine consumption, to our knowledge no study to date has characterized clinically relevant neuropsychological variables along with physiological variables separately in populations of individuals with histories of smoked cocaine dependence (SCD) and insufflated cocaine hydrochloride dependence (ICD). Methods: The present study examined a sample of (a) 25 participants who fulfilled criteria for SCD, (b) 22 participants who fulfilled criteria for ICD, and (c) 25 healthy controls matched by age, gender, education, and socioeconomic status. An exhaustive neuropsychological battery was used to assess different cognitive domains (attention, executive functions, fluid intelligence, memory, language and social cognition). We complemented this neuropsychological assessment with the acquisition and analysis of structural (MRI) and functional (fMRI) neuroimaging data. Results: Different routes of administration led to equally different profiles of neurocognitive impairment, with the SCD group being specifically associated with deficits in attention and executive functions. Consistent with risk models, executive function-attention deficit is better explained for age and age onset of consumption initiation. SCD also presented reduced grey matter density relative to ICD in the bilateral caudate, a key area for executive functions and attention. Connectivity between left caudate and inferior frontal regions mediates performance-structure association. Conclusions: Cocaine routes of administration are associated to a differential profile that may not be due direct effects of stimulant action but also driven by cognitive and biological differences in key executive functioning and attention areas. This point the critical importance of the routes of administration. This information could inform clinical management and should be taken into account in clinical research.