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Understanding and improving human motivational capacities: A focus on glutathione in the ventral striatum

Descripción del proyecto

Metabolismo encefálico y motivación: ¿existe un vínculo?

En la motivación están presentes las fuerzas biológicas y cognitivas que impulsan un comportamiento particular. Dado que la falta de motivación se ha asociado con la depresión, comprender los mecanismos encefálicos subyacentes puede ayudar a diseñar nuevos tratamientos. En el proyecto LGCMOT, financiado con fondos europeos, se trabaja bajo la hipótesis de que el metabolismo en el cuerpo estriado ventral, la parte del encéfalo asociada con el comportamiento motivado, desempeña un papel importante en la motivación. Los investigadores cuantificarán los niveles del antioxidante glutatión y los relacionarán con la actividad neuronal en el cuerpo estriado ventral. Además, probarán el impacto de la intervención nutricional en el comportamiento motivado.

Objetivo

Motivation -the process that facilitates overcoming the cost of effortful actions to attain desired outcomes- is key to achievement and well-being. Importantly, there are major individual differences in motivational levels. Low motivation can reflect states of fatigue or depression not only in patients, but also in the general population, and there is currently no effective treatment to ameliorate this condition. Understanding the brain mechanisms linked to variation in motivated behavior will be of utmost importance to advancing treatments. Brain metabolism in the ventral striatum -a brain’s motivation hub- is emerging as a strong regulator of motivated behaviors. Strong pilot data from the host lab has underscored a striking correspondence between glutathione (GSH) - the most prominent antioxidant – levels in the ventral striatum and motivate on the prediction of effort-based motivated behavior. However, solid evidence is still lacking. The goal of this proposal is to determine whether GSH levels in the ventral striatum relate to widespread levels of effortful performance in healthy human subjects. To this end, I will use a combination of high-field (7T) 1H-Magnetic Resonance Spectroscopy (1H-MRS; to quantify GSH levels in the ventral striatum, and in the occipital cortex as control region), functional Magnetic Resonance Imaging (fMRI; focusing on BOLD activity in the ventral striatum), behavioral testing for physical and cognitive effort-based motivation, and computational modeling (allowing to dissect specific motivational components). In addition, a 7-days nutritional intervention (N-acetyl-cysteine or placebo) to manipulate the GSH system will be tested for its effectiveness to 1) increase striatal GSH levels; and 2) improve specific aspects of motivated behavior (e.g. incentive valuation, effortful performance) in the physical and/or cognitive effort tasks. Therefore, LGCMOT outcomes will greatly advance knowledge in the emerging field of neurometabolism.

Coordinador

ECOLE POLYTECHNIQUE FEDERALE DE LAUSANNE
Aportación neta de la UEn
€ 191 149,44
Dirección
BATIMENT CE 3316 STATION 1
1015 Lausanne
Suiza

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Región
Schweiz/Suisse/Svizzera Région lémanique Vaud
Tipo de actividad
Higher or Secondary Education Establishments
Enlaces
Coste total
€ 191 149,44