Disrupted Functional Connectivity with Dopaminergic Midbrain in Cocaine Abusers

Dardo Tomasi,Frank Telang,Jean H Carrillo,Patricia A Woicik,Thomas Maloney,Ruiliang Wang,Nora D Volkow,Rita Z Goldstein,Nelly Alia-Klein,Pedro Antonio Valdes-Sosa

doi:10.1371/journal.pone.0010815

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.

Highlights

With repeated use, cocaine leads to neuroadaptations in dopaminergic function [1,2,3,4]
Brain activation In both groups, the DW paradigm activated a bilateral network that included the prefrontal cortex (PFC) [caudal dorsal anterior cingulate Brodmann area (BA) 32, inferior (BA 47), and middle (MFG; BA 9) frontal gyri], inferior (BA 40) and superior (BA 7) parietal cortices, thalamus, dorsal striatum, midbrain, and cerebellum and deactivated the parahippocampal (BA 30) and rostral anterior cingulate gyri, precuneus (BA 31), amygdala, and insula (BA 13)
Group comparisons showed that activation was higher for controls than for cocaine abusers in the dorsolateral PFC (MFG BA 9, and precentral gyrus BA 6), cerebellum, thalamus, and left caudate; cocaine abusers deactivated more the rostral anterior cingulate cortex (rACC) than controls

Summary

Introduction

Cocaine leads to neuroadaptations in dopaminergic function (as well as neuroadaptations in other catecholamines and glutamatergic and gabaergic systems) [1,2,3,4] These neuroadaptations could interfere with the functional connectivity of brain regions modulated by dopamine and contribute to the decreased reward sensitivity, enhanced stress reactivity, and executive cognitive dysfunction reported in cocaine abusers [1,5,6,7,8,9]. The fluctuations of neural activity that mediate neuroadaptations [10] can alter dynamically the cerebral blood flow and volume [11] and produce synchronous magnetic resonance imaging (MRI) signals in different brain regions [12] This synchronous MRI signal fluctuations have been used to assess the in-vivo functional connectivity of the human brain in resting-state conditions [13]. 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

Methods

Results

Discussion

Conclusion