Institut de Neurosciences Cognitives et Intégratives d'Aquitaine (UMR5287)

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Home > Teams > ADDICTEAM (M. CADOR) > Thesis defense

Aurélie Fitoussi’s Ph.D December 13th 2011

by Catherine Le Moine - published on , updated on

Aurélie Fitoussi’s Ph.D

Marqueurs comportementaux et corrélats neurobiologiques de la prise de décision adaptée et inadaptée chez le rat.

  • Directrice de thèse: Françoise Dellu-Hagedorn

Abstract: Decision-making is profoundly impaired in several psychiatric disorders such as addiction, but also in some healthy individuals for whom immediate gratifications prevail over long term gain. To better elucidate the neuropsychological and neurobiological bases of good and poor decision making in normal and pathological conditions, healthy poor decision makers represent a promising model. Recently, a Rat Gambling Task (RGT), measuring decision-making process according to the same principle as the Iowa gambling Task in humans, has been validated. Among a majority of good decision-makers, this task allows the identification of a minority of poor decision-makers that prefer immediate larger reward despite suffering large loses. We demonstrated that all poor decision makers are unflexible and less efficient in goal-directed behaviour. They also have a higher motivation for reward that depends on a complex cost/benefice balance, related to the effort to make, to food palatability, but not to the perception of the pleasant feeling or to metabolic needs. Moreover, we demonstrated the absence of relationship between decision making performance and working memory. At the neurobiological level, we demonstrated 1) that efficiency in goal-directed behaviour depends on a right balance within the prefronto-striatal network, strongly linked to decision making abilities and 2) that decision making process depends on specific brain regions, with a level of activity related to performances, as well as the time course to make choices. Higher orbitofrontal cortex and accumbens (Shell) activities are systematically associated with good decision making, whereas the recruitment of prelimbic-cortex-dorsal striatum is modulated according to the time course to make good choices. Anterior cingular and infralimbic cortices, as well as amygdala would be disengaged when choices are established. Poor decision makers display a prefrontal hypoactivity associated with a persistent involvement of amygdala, suggesting an alteration in the prefrontal cognitive control, combined with deficits in reward-based associations, leading to an impaired acquisition and/or reactualisation of the incentive value of the options. Moreover, we demonstrated that inter-individual differences in the RGT are associated with distinct DA- and 5HT basal functions. Poor decision makers notably displayed (1) higher DA- and 5HT-ergic metabolisms in the infralimbic cortex, supporting their motor impulsivity and/or lower efficiency in goal-directed behaviour and (2) a higher DA-ergic metabolism in accumbens (Core), and lower 5HT-ergic in amygdala, that could be related to their stronger motivation, and the quality of reward-based associations. These data support the relationship between genetic polymorphisms inducing distinct basal monoaminergic functioning, and poor decision making as well as psychiatric disorders. All these cognitive/behavioural and neurobiological characteristics that make a consistent framework could be an endophenotype of mental disorders. Further experiments should examine the direct relationship between poor decision making and psychiatric disorders, such as addiction, and the genetic background related to this specific profile.

Keywords: decision making, Rat Gambling Task, behavioural traits, prefronto-subcortical network, dopamine, serotonin, endophenotype, psychiatric disorders, marker of neural activity, HPLC (high performance liquid chromatography).

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