FOR 5159:  Resolving the prefrontal circuits of cognitive flexibility: Dynamic prefrontal representations of cognitive variability

• Subject Area: Medicine
• Term: since 2021
• Website: Homepage
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 437610067

Our environment is constantly changing. Successful survival under these conditions implies that our behavior has to be flexible as well. We experience different places and contexts, have to conduct different tasks in a rapid sequence and need to constantly develop and re-arrange acting strategies. These abilities are not inherited, but develop with age and their regression forms the core of several pathologies. It is commonly held that in mammalian species the prefrontal cortex (PFC) is the hub brain area accounting for the flexibility of minds (i.e. cognitive flexibility). A fundamental aim of neuroscience is to decipher the dynamic principles that govern the ability to cope with a permanently changing environment. Towards this goal, during the 1st funding period, we showed how prefrontal ensembles underlying well-defined aspects of cognitive flexibility (i.e., working memory and decision making) in different mammalian species are formed through temporal coordination and as result of distinct inputs and outputs from other brain regions. Moreover, we observed a large behavioral variability as a core feature of cognitive flexibility, allowing optimal survival and adaptation. Therefore, during the 2nd funding period, in a coordinated and interdisciplinary research effort spanning complementary expertise in different species, concepts, and methodologies, the Research Unit 5159 aims to dissect the features of intra- and inter-individual behavioral variability, identify its sources, and map it onto dynamic representations and activity patterns in the PFC. The working hypothesis is that, behavioral variability emerges as a sum of neural dynamics changes formed through the interplay of intrinsic traits (e.g., sex, age, hormonal status) and extrinsic modifiers (e.g., previous experience, learning, reward). Experimental results from similar monitoring and manipulation of prefrontal circuits will be integrated into computational models with the aim of revealing overarching neuro-dynamical principles of cognitive flexibility that are common to rodents, monkeys, and humans, on the one hand, and the species-specific specialization of prefrontal coding, on the other hand. To foster efficient binding of conceptual and methodological expertise within the consortium, common work packages (and corresponding co-worker exchange) between labs are defined. By these means, we will comprehensively elucidate the prefrontal mechanisms of cognitive flexibility that are critical to understand the survival strategies of mammalian species and represent the basis for future investigations of disease-related disturbances of cognitive flexibility.

• DFG Programme: Research Units
• International Connection: Austria, USA

Projects

• Behavioral history dependent prefrontal neurodynamics of human cognitive flexibility at single-neuron resolution (Applicant Jacob, Simon N. )
• Charting diversity in computational system dynamics and behavioral strategies in cognitive flexibility (Applicant Durstewitz, Daniel )
• Choice-predicting neurons in the prelimbic cortex during a modified Iowa-gambling-task for rats (Applicant Klausberger, Thomas )
• Coordination Funds (Applicant Hanganu-Opatz, Ileana L. )
• Coordination Funds (Applicant Hanganu-Opatz, Ileana L. )
• Deciphering dynamic and stable prefrontal representation of memory contents in mice (Applicants Bartos, Marlene ;  Sauer, Jonas-Frederic )
• (Fe)male rat brain - the effect of sex on the individual behavioral strategies and their neuronal correlates (Applicant Diester, Ilka )
• Identifying mechanisms underlying decision making variability using data-driven optimal control frameworks (Applicant Koppe, Georgia )
• Intrinsic determinants of flexible prefrontal ensembles (Applicant Leibold, Christian )
• Mapping developmental variability of cognitive performance into prefrontal circuits (Applicant Hanganu-Opatz, Ileana L. )
• Mapping variability in prefrontal representations of goal-oriented reward tasks in dependence of learning performance (Applicant Bartos, Marlene )
• Maturation of flexible cognitive behavior as result of age-dependent formation of prefrontal ensembles in juvenile mice (Applicant Hanganu-Opatz, Ileana L. )
• Neural basis of deduced ordinal judgments in the primate prefrontal cortex (Applicant Nieder, Andreas )
• Neuro-dynamic mechanisms of cognitive flexibility at the cellular and microcircuit-level in human dorsolateral prefrontal cortex (Applicant Jacob, Simon N. )
• Prefrontal neuronal correlates of variability in continual learning (Applicant Sauer, Jonas-Frederic )
• Reconstructing neuro-dynamical principles of prefrontal cortical computations across cognitive tasks and species (Applicant Durstewitz, Daniel )
• Relating variability in prefrontal representations and dynamics to behavioral strategy changes (Applicant Sigurdsson, Torfi )
• Resolving the diversity of prefrontal neuron activity within and across behavioral tasks in mice (Applicant Sigurdsson, Torfi )
• State-Dependent Neuronal Variability in Primate PFC During Numerical Judgment (Applicant Nieder, Andreas )

• Spokesperson: Professorin Dr. Ileana L. Hanganu-Opatz