There are important individual differences in motivation, and these differences are key to individuals’ well-being. Motivational alterations are at the core of several pathologies, including neurodegenerative diseases such as Parkinson’s disease or Alzheimer’s Disease and psychopathologies such as major depressive disorder and schizophrenia. Moreover, lack of motivation and increased effort sensitivity relates to a more sedentary lifestyle which is associated with higher risks for cardiovascular disease, diabetes, and cancer. Motivation can be defined as a series of value-based decisions which drive behavior based on a cost-benefit tradeoff between the costs and the expected benefits of an action. Despite considerable advances in the last decades in the neural correlates of value-based decision-making, the biological underpinnings that determine individual differences in effort-based decision-making remain unclear. Increasing evidence is providing strong support to implicate brain metabolism in different motivational components. Effort perception, perseverance, and mental fatigue have been related to specific metabolites, such as glutamine, glutathione, and glutamate in different brain areas related to motivated behavior, such as the ventral striatum and the dorsolateral prefrontal cortex. However, the contribution of specific metabolites, in brain regions crucially involved in decision-making, to brain function and behavior in human subjects is still rather unexplored. Understanding the neuromolecular underpinnings of effort-based decision-making in humans offers great potential for developing treatments and interventions for altered motivation in a wide range of pathologies and in healthy human individuals. In the current project, we assessed how the baseline levels of glutathione, the main antioxidant in the body, of 75 participants (N=40 females) in two different structures of the brain related to motivated behavior, relate to effort-based decision-making. These insights can pave the way for the development of new approaches -e.g. antioxidant treatments- to ameliorate motivational dysfunctions.
