FrontLab

TEAM “FRONTAL FUNCTIONS AND PATHOLOGY”

The FrontLab, directed by Richard Levy, is a research team within the Paris Brain Institute. The general aim of the team is to tackle the neuroscientific aspects of prefrontal functions and translate this knowledge to patient care and assessment.

The prefrontal cortex (PFC) and its related networks act as a hub allowing the coordination of cognitive brain functions required for a highly integrated behavior, critical for non-routine behavior, including exploration behavior, abstract ideation, spontaneous thinking, and creative thinking. It is thus expected that when the PFC and related networks are damaged, these functions are impaired. However, the precise consequences on cognitive abilities and behavior are still poorly described, assessed, and treated. The general aim of our team is to tackle the neuroscientific aspects of these prefrontal functions and translate this knowledge to patient care and assessment. For this purpose, our project is organized into a two-level program. At a first level, we develop cognitive neuroscience projects focused on high-level cognitive functions, from mind-wandering to creativity and reasoning, considering the role of attentional and valuation processes in these functions. At a second level, we develop a translational program focused on pathologies affecting the frontal lobes (such as fronto-temporal dementia/FTD). As described below, the topics of these two levels will reciprocally feed-forward (patients will be included in fundamental first-level projects, while scientific data gathered in the first level will serve to feed and implement the translational level to phenotype and treat patients).

More specific goals at the first neurocognitive level will be to decipher the associative, controlled, valuative, and attentional cognitive mechanisms involved in high-level cognition and characterize them as emerging from interactive and dynamic brain networks. We will focus on high-level cognitive functions such as creativity, analogical reasoning, abstract thinking, cognitive flexibility or inhibition, and mind-wandering. Some of our specific subgoals will be: 1) To build a new cognitive model of creativity involving decision-making processes, with a valuation component interacting with a memory foraging component and a control component for creative idea generation. 2) To identify the mechanisms of problem-solving and examine how they involve a reorganization of our knowledge; 3) To determine how contextual, attentional, emotional, or individual factors can impact idea generation and problem-solving; 4) To determine the attentional and neural markers of mind-wandering and develop cognitive and brain intervention methods to modulate them. In the longer term, our research should allow us to develop new cognitive tools to profile creative ability in individuals based on the identified mechanisms. We also aim to elaborate cognitive training and neuromodulation programs to act on the identified mechanisms and improve sustained attention, problem-solving, and creative cognition.

More specific goals at the second translational level will be three-folded: 1/ we wish to translate the cognitive assessments (creativity, attentional states, abstract thinking...), including web-based tools developed at the "cognitive neuroscience level" to the clinic: i) to better phenotype (in combination with other biomarkers) our cohorts of neurological diseases (e.g., FTD, Alzheimer Disease), ii) to accurately determine the conversion from pre-symptomatic to disease (in particular, in FTD) and iii) to develop markers that can be used to assess treatment efficacy; 2/ we will further develop an original approach consisting in finding behavioral signatures of frontal behavior dysfunctions (apathy, disinhibition, social cognition impairments...) in natural settings, under structured and controlled scenario and paradigms in ecological situations (either close to a real-life situation in the lab (ECOCAPTURE@lab or CogToolkit Labcom projects) or at home (ECOCAPTURE@home) taking advantages of new technologies (e.g., sensors, smartphones). These behavioral signatures will be used to provide a more objective way to assess behavior, to investigate the neural bases of behavioral disorders and ultimately propose new options to treat behavioral disorders; 3/ we would like to pursue our therapeutical approaches using external neurostimulation (TDCs to attenuate cognitive/behavioral disorders in neurodegenerative diseases and develop new tools based on our cognitive neuroscience expertise (including non-pharmological interventions such as neurofeedback) and ecological, behavioral approach (ECOCAPTURE@work) for rehabilitation programs.

Our research will take advantage of an interdisciplinary approach combining experimental psychology (developing new cognitive paradigms or tools), ecological settings and human ethological assessment in natural setting revealing specific behavioral signatures, computational modeling, and multimodal structural and functional neuroimaging methods, including classical MRI and EEG, but also original approaches we developed particular expertise with (brain lesion studies, network-based science, non-invasive neurostimulation, intracranial EEG in implanted patients).

This research program should allow us to clarify the cognitive and neural mechanisms of functions "hubing" in the prefrontal cortex, providing a new framework for high-level cognitive functions and complex behaviors, and how we can influence them. In the long run, it will hopefully lead to applications in improving diagnostic tools for patients and in developing cognitive training programs, with a potential for both a medical and technology transfer.

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Richard levy and Emmanuelle Volle

Richard Levy and Emmanuelle Volle presenting the future of the FrontLab at an ICM conference.