Presentation
My work is at the crossroads of computational, cognitive and system neurosciences. I study learning, decision-making and executive control in rodents and humans, with a strong emphasis on the interaction of these processes with contextual variables such as reward-punishment rate, uncertainty and controllability.
I am part of the Computation, Cognition and Neurophysiology (COPHY) team, and I lead the Adaptive Control group that has received generous funding by INSERM, ATIP-AVENIR program and the European Commission since December 2023 (ERC Starting Grant). Its overarching goal is to find the right balance between theory and experimentation with humans and rodents to foster rapid progress in our understanding of species-invariant mechanisms involved in the regulation of action selection by contextual variables and associated neuromodulatory pathways.
My projects ought to inform clinical research in neuropsychiatry, fundamental theories of adaptive behavior, and artificial intelligence.
ERC Starting Grant project
The acronym CRACK-5HT stands for "Cross-species Regulation of Action by Controllability: a Keystone of 5-HT signaling?" which reflects the ambition to address long-standing issues in clinical and fundamental neuroscience.
- How is controllability signaled and integrated within the forebrain alongside other second-order environmental statistics (e.g. reward rates, uncertainty, volatility) to regulate action selection?
- What are the determinants of endogenous serotonin signaling and how does it interact with other neuromodulators such as dopamine and noradrenaline?
- What are the neurocognitive pathways mediating the behavioral effects of serotonin in health and disease?
To address these questions, the experiments performed by Adaptive Control lab spans three disciplines:
- System neuroscience. Viral vectors and transgenic mice allow us to record and manipulate genetically-defined population of serotonin neurons using light-based techniques, such as optogenetics and calcium imaging.
- Cognitive neuroscience. Neuroimaging allows us to record proxies of whole-brain neural activity (e.g. BOLD signals, oscillations, evoked potentials) in humans performing either simple (i.e., rodent-compatible) and more complex cognitive tasks designed to dissociate the influence of controllability, uncertainty and reward expectation on learning and decision-making.
- Psychiatry. Testing patients suffering from neuropsychiatric disorders (in particular, depression) allows us to evaluate the impact of serotonergic dysfunctions on controllability estimation and downstream cognitive processes.
To integrate data generated by these three approaches within a joint framework able to address our hypotheses, two additional components are essential:
- Computational models for their capacity to probe analogous cognitive processes across tasks and species
- Pharmacological interventions for their applicability to both mice and humans.
Methods used
The Adaptive Control group works with two species: humans and (transgenic) mice. Despite obvious differences in neuroanatomy and cognitive abilities, these two models are very complementary to study the neurocomputational bases of adaptive control.
- On the one hand, the flexibility of human cognition allows investigating multiple cognitive mechanisms (and their interaction) in single individuals and neuroimaging (MEG,fMRI) techniques allows assessing the impact of cognitive tasks, disorders and treatments on the whole-brain with relative ease.
- On the other hand, transgenic lines, viral vectors and invasive techniques permitted by the mouse model allow measuring (calcium imaging, biosensors, Neuropixels) and manipulating (optogenetics) the activity of genetically-defined neurons, thereby enabling us to test highly constrained hypotheses regarding the computations of small neural circuits.
Computational modeling plays a pivotal role to design behavioral tasks able to capture the analogous (or even better: homologous) processes in both species and interpret the data within a unified framework.
Given our interest in neuromodulatory systems, observing similar effects after similar pharmacological manipulations represents another crucial validation step and a real perspective for the translation of system neuroscience into psychological and clinical insights.
The group has direct access to numerous relevant resources at walking distance, including:
- Human neuroimaging and electrophysiology: (f)MRI, PET-(f)MRI, MEG, EEG, sEEG (CERMEP)
- Psychiatry and neurology services collaborating with research units to study various disorders (Vinatier, Hopital Neurologique)
- Rodent neuroimaging: 2-photon microscope, confocal microscope, fluorescence microscopes (Neurocampus)
- State-of-the-art vivarium with authorizations for transgenic/viral approaches (Neurocampus)
- Efficient computing cluster (IN2P3 and in-house grid)
In addition to these common resources, the group currently ordering equipment from leading manufacturers that will be dedicated to our research. Our priority is the acquisition of:
- a multi-animal (up to 6) or multi-site (up to 19) fiber photometry apparatus able to record signals elicited with 3 excitation wavelengths (415, 465 and 565nm)
- several apparatuses for optogenetic stimulation of green and red-shift opsins
- a complete Neuropixels 2.0 recording rig, as soon as it will be commercially available
