Attention is the process that enables us to select the most relevant information that is captured by our senses for further processing, while setting aside the remaining information. It is a complex, multi-faceted function. It involves selecting, at any given moment, information in space as well as in time. In our daily life, we all experience minor attentional lapses: “Sorry, can you just repeat what you just told me?” However, in certain pathological conditions, dysfunctions of attentional processes lead to dramatic impairments. Adults suffering from hemineglect following a stroke, despite normal visual perception, fail to attend to even the most conspicuous and relevant visual stimuli situated on the side contralateral to their brain. In these patients, the attentional deficit is most marked in the space domain of attention. Children, adolescents, and adults suffering from ADHD (attention deficit hyperactivity disorder, a developmental syndrome), have great difficulty in maintaining their concentration on a task long enough to perform it properly. Their deficit is thus most marked in the time domain of attention. One of the common points between hemineglect and ADHD is that both of them can potentially be alleviated by selectively increasing noradrenergic neuromodulation. However, to date, the mechanisms of action by which noradrenergic agonists exert their therapeutical effects remain unknown, and the neural bases of their behavioral effects still need to be described. How does norepinephrine boost up attention? Does it always work? Solving these questions is not only of health care interest; it also of crucial societal importance. Indeed, there exists a growing consumption of attention boosting drugs, also called "cognitive enhancers", by healthy people looking for an extra-edge. For example, drugs initially developed for ADHD, such as Ritalin, are being used by students in pursuit of better grades, military personnel who need to remain awake for long missions, elderly individuals afraid of cognitive decline, and even university academics keen to maintain their performance. The long term effect of this consumption on brain health, brain aging and cognition is unknown. The BOOSTER project will explore the behavioral determinants and neural bases of the attention boosting effect of enhanced noradrenergic neurodomulation. Its ambition is to 1) provide a precise description of the contribution of noradrenergic modulation to local, short-range and long-range neural processes underlying normal attentional function, 2) suggest ways to refine the treatment of attention disorders, such as hemineglect and ADHD, and 3) quantify the effectiveness of noradrenergic agonists as attention boosters for healthy people looking for an extra edge and issue healthcare safety guidelines. BOOSTER is the joint endeavor of two Lyon laboratories that have been nurturing close methodological cooperation and frequent scientific exchanges for years now. The project’s originality lies in the use of a multi-level approach combining a thorough behavioral investigation of the noradrenaline agonists with 1) the whole-brain approach afforded by fMRI (Partner 1) and 2) the high-spatial resolution of fMRI-guided single-cell and LFP recordings (Partner 2) in the most powerful animal model of human brain functions and dysfunctions.

The sensorimotor system has been widely studied during the last decades, yet little is known about the neural substrate of high-level aspects of movement such as intention and awareness and how these are related to movement execution processes. It has been proposed that the posterior parietal cortex and supplementary motor area are involved in generating motor intentions, while premotor cortex may play a key role in the emergence of motor awareness. However, the precise mechanisms implemented within each of these areas, the way they interact functionally and the nature of the signals they convey to primary sensory and motor regions is far from being understood. Ultimately, intention and awareness of movement are influenced by peripheral afferences coming from the eyes, skin, muscles and joints and this flow of information must be integrated to produce smooth, accurate and coordinated motor actions; but here again, little is known about the mechanisms that underlie this integration. In this project we will investigate how the cortical regions responsible for attributing intention and bringing movement to consciousness share information, integrate sensory signals and update the course of actions. We will address these issues using an integrated methodological approach making use of (i) peri-operative recordings in patients undergoing brain surgeries; (ii) psychophysics in healthy subjects and patients with focal brain lesions; (iii) single pulse and theta burst transcranial magnetic stimulation in healthy subjects; and (iv) functional MRI in healthy subjects. The close cooperation established between a research team specialized in sensorimotor neuropsychology (M Desmurget) and a neurosurgical group expert in peri-operative cerebral mapping (C Mottolese) provides a unique opportunity to carry out this ambitious research. Fundamental, clinical and societal outcomes are expected from this project. At a fundamental level, it should substantially improve our current understanding of the cerebral processes that mediate conscious intentions and motor awareness. At a clinical level, it should have a direct impact on the peri-operative mapping procedures used to minimize post-operative sequelae in patients with brain tumors. Also, it should provide a framework for understanding how abnormalities of conscious intention and action awareness can arise following acute or degenerative cerebral damages. Finally, at a societal level, this project should have major philosophical and ethical implications. In particular, it may contribute to reshape our approach of major societal issues such as personal merit or individual responsibility.

Although social decision making is ubiquitous and central to human society, its underlying neural mechanisms remain poorly understood. There is a need for understanding social decision processes at different levels, bridging the gap between fundamental computational principles and the brain system level. In particular, the fact that complex social decision making relies on probabilistic knowledge about the possible outcomes of choices and on the intentions and cooperativeness of other individuals has been underappreciated. The current project seeks a better understanding of the psychological and neurobiological basis of social decision-making in humans. We propose to develop a new theoretical computational neuroscience framework of social decision making. We will adopt a combination of interdisciplinary perspective, combining Bayesian models and multimodal neuroimaging, i.e. intracranial recordings (iEEG) in humans and fMRI, to investigate the neural mechanisms of decision making processes in social context. The general goal is to characterize the computational principles and the neural mechanisms underlying social decision making. Our main hypothesis is that when we are in an interactive social setting, our brain performs Bayesian inferences using probabilistic representations of other individuals’ intentions and cooperativeness. We will use such probabilistic approaches as Bayesian inference and partially observable Markov decision processes (POMDP) to model ways in which we might predict hypothetical action outcomes, the intentions of others and whether the other is cooperative or competitive. This theoretical framework will be tested by parallel experiments in humans exploiting maximally the experimental advantages of two complementary methodological approaches: 1) model-based fMRI using Bayesian models of social interactions in healthy adults, which should specify the relationships between the neural mechanisms, behavior and the patterns of brain activation; 2) iEEG in patients with epilepsy, which is key for a comprehensive description of the temporal dynamics of populations of neurons engaged in social computations. This original approach will allow us to record spikes from single cells and Local Field Potentials (LFPs) and to perform simultaneously fMRI and iEEG in humans. The locations of neural circuits active when people make decisions in a social setting have been identified. Key components include the ventromedial prefrontal cortex (vmPFC), the dorsomedial (dmPFC) and dorsolateral prefrontal cortex (DLPFC), parts of superior temporal sulcus (STS) including the temporo-parietal junction (TPJ) and the anterior cingulate gyrus (ACCg). Recording from this social brain network, the specific goals of this proposal are to: (1) Unveil the computational mechanisms underlying the neural processes involved in social decision making and integrate them within the more general framework offered by POMDP models that explain how actions are selected in different contexts; (2) Characterize the neural mechanisms for inferring other's intended action; (3) Characterize the neural dynamics of neuronal populations from components of the social brain network when learning social hierarchy and when viewing faces varying in dominant features. (4) Link computational processes for social cognition (aim 1) with neuronal activity, LFPs and BOLD signal (aims 2&3). In addition to discover whether Bayesian inferences can provide the insights regarding the computational algorithms adopted by the brain to infer the intentions of others, the ground-breaking nature of this research is to: (a) establish a mechanistic foundation for understanding the neurocomputational mechanisms underlying social choice behaviour; (b) provide a multilevel understanding of social decisions, from the system-level to the level of neuronal populations; (c) characterize the spatio-temporal neural dynamics of the social brain structures engaged in social decisions.

The general objective of the project is to investigate the role of multisensory integration in the ability to recognize and understand facial emotion, by considering both developmental aspects in infancy and neuropsychological aspects in schizophrenia. The main hypothesis is that multisensory integration boosts the ability to recognize facial emotion and its development by the way of matching between own facial reactions to multisensory stimulation and facial expression of conspecifics. One question is how and when such a matching mechanism might influence facial expression processing. This issue will be addressed in studying healthy adults in using both behavioral and electrophysiological approaches. We will also investigate the role of matching self-generated expressions and expressions of others by studying patients with a deficit in both aspects of expressiveness and recognition of expressions; namely, schizophrenic patients. The second hypothesis is that non-visual sensory modalities may shape and constrain the matching process. Each modality has its own sensory processes and hedonic properties, and positive/negative feelings arise from these specific sensations. A direct consequence is that no modality will integrate the emotional environment in the way that corresponds to facial emotion categories (e.g., happiness, anger, disgust, fear, and sadness), at least before the learning of associations. Thus, multisensory integration not only promotes coupling processes between self-generated expressions and expressions from others, but they can also shape them according to the characteristics of every modality, and according to their development. We will test this hypothesis in infants. This project will include three main tasks. The first task will hold on healthy adults. The main objective will be to understand whether, how, and when the olfactory context influences facial emotion recognition. In experiment 1, we will study the influence of the olfactory context on facial emotion categories to assess whether the boundaries of these categories are flexible as a function of the emotional meaning of the odour. In experiment 2, we will study the potential early influence of the olfactory context on visual attention, using a visual search paradigm. Finally, in experiment 3, we will study further at which (temporal) level the olfactory context is integrated, using ERPs recordings. The second task will include infant’s studies. The purpose here will be to see whether infants can associate odour-induced feelings and facial expressions and, in case of positive answer to this first question, at which age. In experiment 4, we will study infants’ matching abilities between an odour and dynamic facial expressions. In experiment 5, we will study whether the olfactory context elicits an infant’s expectations for specific facial actions in neutral static expressions. Finally, in experiment 6, we will study whether infants are able to integrate the emotional states of their mother from stress-elicited body odours, and if they express expectations for specific facial information. Finally, in the third task, we will study schizophrenic patients, who are known to have both a deficit in facial expression recognition and a deficit in expressiveness (i.e., flat affect). The purpose of this task will be to assess whether the deficit of facial expressiveness in schizophrenia may influence both the categorical perception of facial expression and the contextual effect of olfactory stimulations. To test for this hypothesis, we will adapt experiment 1 and experiment 3 (task 1) to the study of schizophrenic patients. This approach, coupling cognitive psychology, developmental psychology, ethology and neuropsychology, will allow a better apprehension of processes going on during multisensory integration and facial emotion recognition/understanding by confronting human cognitive and emotional processes at different stages: either mature, under acquisition, or altered.