Disrupted Functional Connectivity with Dopaminergic Midbrain in Cocaine Abusers

Abstract

BackgroundChronic cocaine use is associated with disrupted dopaminergic neurotransmission but how this disruption affects overall brain function (other than reward/motivation) is yet to be fully investigated. Here we test the hypothesis that cocaine addicted subjects will have disrupted functional connectivity between the midbrain (where dopamine neurons are located) and cortical and subcortical brain regions during the performance of a sustained attention task.Methodology/Principal FindingsWe measured brain activation and functional connectivity with fMRI in 20 cocaine abusers and 20 matched controls. When compared to controls, cocaine abusers had lower positive functional connectivity of midbrain with thalamus, cerebellum, and rostral cingulate, and this was associated with decreased activation in thalamus and cerebellum and enhanced deactivation in rostral cingulate.Conclusions/SignificanceThese findings suggest that decreased functional connectivity of the midbrain interferes with the activation and deactivation signals associated with sustained attention in cocaine addicts.

Neuropsychological effects associated with recreational cocaine use

“…ecstasy/MDMA, cannabis, alcohol and nicotine) and in some cases (inhibitory control for example) deficits were related to lifetime cocaine exposure (Colzato et al, 2007). Impairments were similar, but smaller in magnitude, to those observed in chronic users which are commonly attributed to dopaminergic malfunction (Bolla et al, 2001;Tomasi et al, 2010) suggesting that even recreational use of cocaine might begin to compromise dopaminergic pathways.…”

“…Volkow Tomasi et al, 2010), as highlighted by Colzato et al (2009a) it is also possible that a number of pre-existing factors might account for the observed cognitive deficits either directly or via increasing the likelihood that certain individuals will use the drug. Such vulnerability factors might include cognitive disturbance (Bechara, 2005), dopaminergic receptor dysfunction (Nader et al, 2006) or preexisting personality traits, such as impulsivity (Verdejo-Garcia et al, 2008) or schizotypy.…”

The cerebellum in drug craving

“…However, impairment in functional connectivity between frontal cortex, midbrain, anterior cingulate cortex and the vermis (Tomasi et al, 2010) and between cerebellum and nucleus accumbens has also been described (Froeliger et al, 2015). Remarkably, Nacetylcysteine reversed such impairment and reduced craving scores (Froeliger et al, 2015).…”

“…This region exerts an inhibitory effect on drug seeking (Goldstein and Volkow, 2011;Tang et al, 2015). Importantly, craving suppression was inversely correlated with the activity of this prefrontal area (Volkow et al, 2010).…”

Modeling Causal Relationship Between Brain Regions Within the Drug-Cue Processing Network in Chronic Cocaine Smokers

“…A few fMRI studies involving cocaine users have used functional connectivity analysis, which involves correlating activity in spatially remote brain regions (Friston, 1995a), but the results are mixed. Relative to controls, cocaine users have shown enhanced as well as reduced functional connectivity between brain areas during resting state (Cisler et al, 2013;Gu et al, 2010;Wilcox et al, 2011), as well as during an attention and a motor task (Hanlon et al, 2011;Tomasi et al, 2010). According to Cisler et al (2013), cocaine users had an enhanced functional connectivity of the insular cortex with prefrontal networks compared with controls.…”