At the Lyon Neuroscience Research Center (CRNL), David Thura is deciphering the brain mechanisms at the interface between decision and action. He pairs in vivo experiments with computational modeling in his exploration of cortical and subcortical brain regions. Thanks to funding from the Atip-Avenir program, the researcher intends to further elucidate the neural system implicated in regulating decision-making and movement, with another – more applied – objective in his sights: improving the treatment of cognitive impairment in Parkinson’s disease patients.
Neuroscientist Thura has always had a keen interest in decision-making and action. "More specifically, my aim is to describe the brain mechanisms which regulate these functions, which determine the point at which a choice can obtain the most precise action possible, depending on the context and the information available in the environment", he explains. In order to do this, he joined Denis Pélisson’s IMPACT team at CRNL following receipt of his Atip-Avenir funding. With 180,000 euros over 3 years and the possibility of hiring a postdoctoral fellow for a period of 2 years, this program enables young researchers to set up their own research teams. And this is precisely what Thura intends to do, once he has made the most of the stimulating environment of IMPACT to set up and develop his laboratory.
His is a three-pronged experimental approach, involving behavioral experiments in humans and macaque monkeys – animal models commonly used in this field, the measurement of neural electrical activity in these monkeys, and the development of mathematical models of the neural networks involved in order to validate the experimental data and propose the formalization of these mechanisms.
A dialogue between cortical and subcortical regions
His postdoctoral fellowship at the University of Montreal was where Thura had begun to study the neural structures implicated in decision-making and where he acquired the necessary technical skills, such as multi-electrode recording of brain activity. Furthermore, it was the data that he obtained then which have guided the novel hypothesis that he wishes to test now. "It would appear that cortical structures involved in decision-making and action, particularly the premotor and primary motor cortex, are influenced by the basal ganglia – subcortical structures which are older in evolutionary terms and with highly diverse functions, ranging from low level motor control to regulating the value of an action and learning through reinforcement", details the researcher. In addition to the approach conducted in animals, his host laboratory will enable him to perform behavioral experiments in humans.
While there is a highly fundamental component to the project, it could ultimately provide information useful for the clinical field. "Disruptions in basal ganglia function occur notably in Parkinson’s disease", notes Thura. "Yet in addition to motor disorders, these patients present with cognitive disorders, including difficulties making decisions". Knowledge of the precise physiological decision-making circuit could therefore make it possible to improve understanding of why pathological cognitive disorders are often observed in such patients and, ultimately, to reduce these disorders through more specific targeting of the basal ganglia cells involved in regulating decision-making.
A springboard for recruitment
This highly comprehensive approach earned Thura the Atip-Avenir funding in 2017. "Without doubt the best funding for launching a career in France, and above all a springboard for recruitment as a tenured researcher", he emphasizes, referring to his recruitment by Inserm in 2018. The Atip-Avenir funding has been invested in equipment including experimental materials for use with monkeys and the researcher will recruit a postdoctoral fellow in December. "This most gratifying selective funding drew me back to France, following various interviews in the USA and Canada. I was really keen to work at CRNL, in this laboratory with its theoretical expertise in the field, a first-class primate facility, and functional MRI for potential experiments on monkeys and humans.”
David Thura is an Inserm Research Officer in the IMPACT (Integrative, Multisensory, Perception, Action and Cognition) team at the Lyon Neuroscience Research Center (unit 1028 Inserm/CNRS/Université Saint-Etienne - Jean Monnet/Université Claude Bernard Lyon 1).