Periodic Reporting for period 2 - SOCIALEYES (Neural origins of mind reading)
Período documentado: 2022-03-01 hasta 2023-08-31
The project "Neural Origins of Mind Reading" aims to elucidate the neural and evolutionary origins of human social cognition. It addresses questions such as: What makes us able to understand the behaviours, affective states and intentions of our social partners? What are the sources of information we rely on to do this? How do we regulate our own behaviours in response to the signals that others send us and how do we communicate our own intentions?
These questions are important because humans, like all other primates, are highly social and because learning to navigate dense and complex networks of social interactions is a long and difficult process, essential to our individual well-being and ultimately to our survival as a species. Moreover, there is ample evidence that social experience combines with genetic predispositions to shape the structure and function of our brains and determine how we process and respond to social cues. We still have only a limited knowledge of these mechanisms and a more complete understanding could be useful, especially in improving or inventing new strategies and treatments to help people who have difficulty adapting to the demands of social life.
The project’s acronym SocialEyes underlines the particular angle that has been chosen to address this broad topic. It emphasises the importance of a conserved non-verbal signalling that is ubiquitous in non-human primates, namely the use of eyes and gaze to express interest in others, to direct their attention, to convey affiliative or, conversely, agonistic intentions. Behaviours such as gaze following and joint attention appear very early in infant development and are precursors to more sophisticated social cognitive skills, such as inferring the intentions and beliefs of others. They are often the prelude to more elaborate social interactions, both in the affiliative domain (social proximity, cooperation, social grooming) and in the agonistic domain (assertion of social status, threat and aggression).
The aim of the present project is to uncover the neural basis of these cognitive specialisations. Our research investigates the role of ancient structures and neural signalling pathways that are well conserved across the primate order, focusing on the brain and behavioural mechanisms that support social attention and mind reading in the macaque monkey.
These questions are important because humans, like all other primates, are highly social and because learning to navigate dense and complex networks of social interactions is a long and difficult process, essential to our individual well-being and ultimately to our survival as a species. Moreover, there is ample evidence that social experience combines with genetic predispositions to shape the structure and function of our brains and determine how we process and respond to social cues. We still have only a limited knowledge of these mechanisms and a more complete understanding could be useful, especially in improving or inventing new strategies and treatments to help people who have difficulty adapting to the demands of social life.
The project’s acronym SocialEyes underlines the particular angle that has been chosen to address this broad topic. It emphasises the importance of a conserved non-verbal signalling that is ubiquitous in non-human primates, namely the use of eyes and gaze to express interest in others, to direct their attention, to convey affiliative or, conversely, agonistic intentions. Behaviours such as gaze following and joint attention appear very early in infant development and are precursors to more sophisticated social cognitive skills, such as inferring the intentions and beliefs of others. They are often the prelude to more elaborate social interactions, both in the affiliative domain (social proximity, cooperation, social grooming) and in the agonistic domain (assertion of social status, threat and aggression).
The aim of the present project is to uncover the neural basis of these cognitive specialisations. Our research investigates the role of ancient structures and neural signalling pathways that are well conserved across the primate order, focusing on the brain and behavioural mechanisms that support social attention and mind reading in the macaque monkey.
The programme of work is built around a framework that emphasises the role of a subcortical network comprising the hypothalamic oxytocin system, the amygdala and the superior colliculus in social attention and 'mind-reading', i.e. our ability to accurately interpret non-verbal cues produced by other individuals, which underpins a wide range of social behaviours. The methodology adopted combines behavioural approaches (cognitive laboratory tasks, WP1; naturalistic tasks in a semi-ethological setting, WP4) and brain-level approaches (neural recordings, WP2; reversible oxytocin activation and inactivation, WP3). The work in WP1 since the beginning of the project aimed to implement a novel attention coordination task in which monkey subjects learned to engage in joint attention with a realistic and interactive monkey avatar. Preliminary results show that monkeys can follow gaze cues from their avatar partner and coordinate their behaviour with it in a flexible manner.
This task will be used in WP2 to investigate the role of key subcortical structures in encoding the significance of other’s gaze shift. WP2 also aims to provide a comprehensive characterisation of neural functional specialisations with regard to social signal processing. To this end, we recorded, for the first time, the response properties of neurons in two oxytocin-rich hypothalamic subregions, the paraventricular (PVN) and supraoptic (SON) nuclei. Preliminary results highlight the sensitivity of PVN and SON neurons to different sensory stimuli (visual, acoustic, tactile), with some of them showing a preference for social over non-social stimuli. These results provide new insights into the responsiveness of the oxytocin (OT) system and provide a better understanding of how oxytocin dynamically shapes adaptive social behaviour in primates.
In WP3, we are pioneering the of use DREADDs, a technology similar to gene therapy, to enable the selective and reversible activation of oxytocin neurons in the monkey brain. In short, a viral vector is used to introduce new genetic material into OT neurons, so that these cells begin to express an excitatory receptor. This receptor can then be activated by administration of its ligand, resulting in activation of the neurons and release of oxytocin. We found that activation of OT neurons modulated the monkeys' visual attention, significantly increasing the time spent exploring socially relevant information, and in particular the eye region, in images of conspecifics. We were also able to verify that DREADD expression was restricted to OT neurons, using an immunohistochemical approach on ex-vivo brain tissue.
WP4 extends our study of social behaviour into an ethological framework allowing us to conduct brain/behaviour studies in socially interacting monkeys that move freely and express species-specific behaviour without constraint. Work in WP4 since the beginning of the project has included the development of automatic behaviour recognition from video recordings using state-of-the-art machine learning approaches, the implementation of a behavioural paradigm to test the effects of endogenous oxytocin, the collection of neural data using a wireless recording device. In the latter task, we recorded from regions of the frontal cortex while the monkeys performed kinematically similar, but different actions depending on whether they occurred in a social or non-social context (e.g. grasping during foraging or during social grooming). Most interestingly, the recorded cellular activity showed context-dependent modulation and specific responses to vocalisations.
This task will be used in WP2 to investigate the role of key subcortical structures in encoding the significance of other’s gaze shift. WP2 also aims to provide a comprehensive characterisation of neural functional specialisations with regard to social signal processing. To this end, we recorded, for the first time, the response properties of neurons in two oxytocin-rich hypothalamic subregions, the paraventricular (PVN) and supraoptic (SON) nuclei. Preliminary results highlight the sensitivity of PVN and SON neurons to different sensory stimuli (visual, acoustic, tactile), with some of them showing a preference for social over non-social stimuli. These results provide new insights into the responsiveness of the oxytocin (OT) system and provide a better understanding of how oxytocin dynamically shapes adaptive social behaviour in primates.
In WP3, we are pioneering the of use DREADDs, a technology similar to gene therapy, to enable the selective and reversible activation of oxytocin neurons in the monkey brain. In short, a viral vector is used to introduce new genetic material into OT neurons, so that these cells begin to express an excitatory receptor. This receptor can then be activated by administration of its ligand, resulting in activation of the neurons and release of oxytocin. We found that activation of OT neurons modulated the monkeys' visual attention, significantly increasing the time spent exploring socially relevant information, and in particular the eye region, in images of conspecifics. We were also able to verify that DREADD expression was restricted to OT neurons, using an immunohistochemical approach on ex-vivo brain tissue.
WP4 extends our study of social behaviour into an ethological framework allowing us to conduct brain/behaviour studies in socially interacting monkeys that move freely and express species-specific behaviour without constraint. Work in WP4 since the beginning of the project has included the development of automatic behaviour recognition from video recordings using state-of-the-art machine learning approaches, the implementation of a behavioural paradigm to test the effects of endogenous oxytocin, the collection of neural data using a wireless recording device. In the latter task, we recorded from regions of the frontal cortex while the monkeys performed kinematically similar, but different actions depending on whether they occurred in a social or non-social context (e.g. grasping during foraging or during social grooming). Most interestingly, the recorded cellular activity showed context-dependent modulation and specific responses to vocalisations.
Central activation of oxytocin neurons with DREADDs is a powerful tool to causally assess the impact of oxytocin on social information processing at the neural and behavioural level. Our results show, for the first time, that this approach can be used in primates. Although a distant prospect in the context of this project, this could pave the way for the development of new therapeutic approaches for severe social dysfunction in autism spectrum disorders. Another encouraging and pioneering achievement is our success in wirelessly recording single neurons in animals during natural social interactions. We hope that in the second part of the project we will record further high-quality and scientifically rich brain activity in deep brain structures and combine this approach with OT neuron activation and inactivation with DREADDs.