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  • Addiction, Drugs
  • Information from Lay-Language Summaries is Embargoed Until the Conclusion of the Scientific Presentation

    157—Drugs of Abuse: Toxicity and Structural Plasticity

    Sunday, November 10, 2013, 8:00 am - 12:00 noon

    157.18: Abnormal functional and structural cortico-striatal connectivity associated to reward processing in cocaine dependence

    Location: Halls B-H

    *J. RIBA1, L. VAQUERO2, J. BOUSO1, E. C¡MARA2, J. P…REZ DE LOS COBOS3, F. BATLLE3, J. F¡BREGAS4, J. SALES5, M. CERVANTES5, X. FERRER6, G. LAZCANO6, A. RODRÕGUEZ-FORNELLS2;
    1Hosp. De Sant Pau, Barcelona, Spain; 2Cognition and Brain Plasticity Unit, IDIBELL-Bellvitge Biomed. Res. Inst., Barcelona, Spain; 3Addictive Behaviours Unit, Dept. of Psychiatry, Hosp. de Sant Pau, Barcelona, Spain; 4Ctr. d'InvestigaciÛ i Tractament d'Addicions, CITA, Barcelona, Spain; 5Grup ATRA, Barcelona, Spain; 6Fndn. Hlth. and Community, Barcelona, Spain

    Abstract Body: Current models of addiction postulate that altered processing of natural incentives and deficits in cognitive control are key features of drug dependence. However, contrasting hypotheses have been put forward regarding the capacity of non-drug incentives to recruit the reward circuit in drug-dependent individuals. The reward deficiency theory posits that drugs of abuse are taken to normalize an otherwise hypoactive reward circuit; whereas an alternative theory postulates that drug addiction arises from an overall hyperactive reward circuit associated with decreased avoidance due to impaired cognitive control. In order to test these alternative hypotheses, here we measured fMRI BOLD activation associated with monetary gains and losses in a gambling task in a group of 30 cocaine-dependent (CD) individuals and 30 controls. We also investigated potential differences in both gray matter and white matter integrity. The two samples were matched in age, sex, years of education and verbal and procedural IQ. All CD subjects were detoxified inpatients, free of concomitant psychiatric disorders and were not taking any psychotropic medication at the time of assessment. Compared to controls, cocaine users showed increased general reactivity to rewards, evidenced as greater activation following monetary gains in the left and right ventral striatum, orbitofrontal cortex and posterior cingulate cortex. On the other hand, cocaine users showed decreased activation following monetary losses in the anterior cingulate cortex. The structural analysis using voxel-based morphometry showed alterations in the basal ganglia, with increased gray matter volume in the dorsal striatum of CD patients. Integrity of the white matter tracts, as measured using fractional anisotropy, was found to be increased in the ventral striatal and orbitofrontal regions and decreased in the anterior-posterior association bundles. These results support the hypothesis that cocaine dependence is associated with increased general sensitivity to non-drug rewards and decreased behavioral monitoring. Chronic cocaine use leads to changes in structural connectivity in the orbitofrontal cortex and basal ganglia to the detriment of connectivity outside the cortico-striatal reward circuit.

    Lay Language Summary: The repeated intake of substances that produce pleasure and euphoria can lead to addiction. Addiction is a chronic relapsing disease in which the person loses control over their drug use despite the increasing negative impact on their health and the well-being of those around them.
    Scientists have been trying to understand why addiction develops in the first place and why it is so difficult to stop using drugs. They believe that drug addiction changes the way the brain processes stimuli that are normally pleasant to healthy individuals. Drugs of abuse interact with the so-called “reward circuit”, a series of interconnected brain structures that process pleasurable environmental stimuli, such as eating, earning money or spending time with friends. The addicted person also shows deficits in cognitive control, that is, the capacity to regulate their own behavior, for instance avoid the compulsive intake of harmful drugs.
    However, contrasting theories have been put forward regarding the capacity of “rewarding”, i.e., pleasant, non-drug stimuli to activate the reward circuit in drug-dependent individuals. One of these theories, the “reward deficiency theory” proposes that drugs of abuse are taken to normalize a hypoactive reward circuit. Addicts would carry on taking drugs in order to increase activation in brain regions that no longer respond to natural pleasant stimuli. An alternative theory postulates that drug addiction is the consequence of an overall hyperactive reward circuit. Vulnerable individuals would release large amounts of the neurotransmitter dopamine in this circuit. This would be associated to increased impulsivity and to decreased avoidance of negative behaviors due to impaired cognitive control.
    In our study we tested these alternative hypotheses. Using a brain imaging technique we measured brain activation associated with monetary gains and losses in a group of 30 cocaine-dependent (CD) individuals and 30 controls. We also investigated differences in brain structure. The two samples had the same men/women ratio, equivalent age, years of education and intelligence. CD subjects had no psychiatric disorder other than cocaine addiction. At the time of the assessment they were not taking any medications that could affect brain function.
    Brain activation in CD patients carrying out a gambling task showed greater general reactivity than that in controls following monetary gains. This hyperactivity was seen in key structures of the reward circuit, especially in the ventral striatum, a deep area of the brain. In addition to this greater sensitivity to a natural reward, CD patients showed decreased activation following monetary losses in the anterior cingulate cortex, a key area in the cognitive control circuit. Thus, CD patients showed less sensitivity to the adverse consequences of behavior (in this case, losing money).
    Besides these functional differences, the analysis of brain structure in CD patients also showed physical alterations. First, an increase in the volume of gray matter was observed in the dorsal striatum, a structure of the reward circuit associated with compulsive behavior. Second, nerve connections (white matter tracts), within the reward circuit were stronger, while nerve connections outside this circuit were weaker than in control subjects. These weakening of pathways outside the reward circuit negatively affects the transfer of information between brain regions.
    These results support the hypothesis that cocaine dependence is associated with increased sensitivity to rewards and decreased control of behavior. Chronic cocaine users display a disproportionate activity of the reward circuit and structural changes that potentiate compulsive behaviors. This occurs simultaneously with a weakening of connections outside the reward circuit that are essential for normal cognitive function.