H2020Индивидуална стипендия2021–2023

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

„Хоризонт 2020“ — Действия „Мария Склодовска-Кюри“

Период: 2021-05-01 → 2023-04-30
Финансиране от ЕС: 191 149 €
Участници: 1
Схема: MSCA-IF

Линиите свързват координатора с партньорите.

Накратко на български

Метаболитите в мозъка, като глутатиона, влияят върху това как човек преценява усилията спрямо ползите при вземане на решения. Разбирането на тези процеси помага за разработването на методи за подобряване на мотивацията при различни заболявания и при здрави хора.

Този кратък обзор е генериран от изкуствен интелект

Кратко обяснение, генерирано от езиков модел по текста на CORDIS. Оригиналът е по-долу.

Резултати накратко

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

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.

Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз

Цел на проекта

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.

Оригинален текст от CORDIS (на английски).

Участници

ECOLE POLYTECHNIQUE FEDERALE DE LAUSANNE · LausanneКоординаторШвейцария