Periodic Reporting for period 4 - WIRELESS (Motor and cognitive functions of the monkey premotor cortex during free social interactions)
Berichtszeitraum: 2021-04-01 bis 2022-03-31
Non-human primates (NHPs) represent an essential animal model for studying the neural mechanisms underlying several brain functions and dysfunctions they share with humans in various high-order sensorimotor and cognitive domains. Motor actions and social interactions represent two of these domains, which have been shown to be based on shared neural substrates by accumulating neuroscientific evidence of the last three decades. A number of neurological and neuropsychiatric diseases affect the organization and control of voluntary actions and social interactions, respectively, rendering crucial a better and deeper understanding of the neural bases underlying these functions. However, neurophysiological studies in both humans and NHPs have been always performed on “still brains”, mostly because of technical constraints, limiting the range of behaviors that can be explored, the variety of questions that can be addressed and the ecological relevance of the discoveries. Understanding the neural mechanisms underlying motor actions and social interactions requires to primarily investigating freely moving brains in freely moving subjects.
Technological progresses have made possible the miniaturization of devices for wireless neural recordings and the development of video behavioral monitoring systems. By synchronizing multiple sources of data we can study the relationship between brain functioning and behavior in freely-moving subjects, tackling problems and settings previously inaccessible to neuroscientific investigation.
The main final aim of this project is to develop a new approach to the study of brain functioning in non-human primates with single neuron resolution, by exploiting technological innovations that allows us to record single neuron activity in well-controlled laboratory conditions and to compare these findings with those obtained in a novel environment for studying freely moving animals. We aim to validate the new approach by comparing results obtained with state-of-the-art laboratory studies of neuronal properties in different brain areas with wireless recordings carried out in the new setting we called “NeuroEthoRoom” (NER). The main goal is to demonstrate the feasibility of the new approach by proving its validity and reliability, as well as by expanding the current neuroscientific knowledge on the functions and mechanisms underlying motor control and social interactions.
Technological progresses have made possible the miniaturization of devices for wireless neural recordings and the development of video behavioral monitoring systems. By synchronizing multiple sources of data we can study the relationship between brain functioning and behavior in freely-moving subjects, tackling problems and settings previously inaccessible to neuroscientific investigation.
The main final aim of this project is to develop a new approach to the study of brain functioning in non-human primates with single neuron resolution, by exploiting technological innovations that allows us to record single neuron activity in well-controlled laboratory conditions and to compare these findings with those obtained in a novel environment for studying freely moving animals. We aim to validate the new approach by comparing results obtained with state-of-the-art laboratory studies of neuronal properties in different brain areas with wireless recordings carried out in the new setting we called “NeuroEthoRoom” (NER). The main goal is to demonstrate the feasibility of the new approach by proving its validity and reliability, as well as by expanding the current neuroscientific knowledge on the functions and mechanisms underlying motor control and social interactions.
We conceived and build an innovative setup for wireless recordings, the “NeuroEthoRoom” (NER), to simultaneously study non-human primates (NHPs) behavior and brain activity during unconstrained situations. The NER is a large transparent enclosure in which up to two animals can freely move, monitored by a system of multiple cameras, enabling to track their position and body movements, simultaneously with wirelessly recorded neuronal activity. Two pairs of macaque monkeys participated in the project, being trained to 1) perform a set of classical visuomotor tasks in head-restrained and head-free situations (including a “social interaction task”) and 2) enter in the NER, with positive reinforcement techniques .
We could automatically track the monkey’s position during natural behaviors in multiple sessions within the NER. We could also extract information about head rotation, roll and pitch. We recorded two animals in both the chair and NER conditions, and the other two in the chair with both head-fixed and head-free conditions, collecting data on a variety of motor behaviour, space coding, and a variety of unconstrained behviours based on wirelessly recorded neuronal activity during freely-moving sessions.
In parallel, we developed and tested new solution for neural recordings and stimulation, in state-of-the-art laboratory conditions. These studies yielded important technical validation data for innovative multi-site recording and stimulation devices. We also demonstrated, with recordings in classical chair settings, various neural mechanisms, hypothesized in the project, concerning the neural bases of other’s observed action processing in the cortical motor system, action organization, and context-based prediction of others’ behavior during social interaction.
These findings have been presented in, so far, in 15 papers published in peer-reviewed international journals and about 12 international conference abstracts (further 3 paper are in preparation and 1 is under second round of revisions).
In sum, despite the difficulties and delays imposed by the pandemic situation, and thanks to the 6 month of extension obtained for the project, we have been able to achieve all the main scientific results in terms of data collection and we are finalizing the publication of some additional important papers the directly derive from the project activities.
Existing, interdisciplinary collaboration of the PI have been consolidated during this period; several PhD students and research fellows have been enrolled, one researchers have got a tenure-track position and other two a position as a fixed-term researchers (at Unipr and Unito). Thus, the project has strongly supported training and initial stage of career of future independent researchers.
We could automatically track the monkey’s position during natural behaviors in multiple sessions within the NER. We could also extract information about head rotation, roll and pitch. We recorded two animals in both the chair and NER conditions, and the other two in the chair with both head-fixed and head-free conditions, collecting data on a variety of motor behaviour, space coding, and a variety of unconstrained behviours based on wirelessly recorded neuronal activity during freely-moving sessions.
In parallel, we developed and tested new solution for neural recordings and stimulation, in state-of-the-art laboratory conditions. These studies yielded important technical validation data for innovative multi-site recording and stimulation devices. We also demonstrated, with recordings in classical chair settings, various neural mechanisms, hypothesized in the project, concerning the neural bases of other’s observed action processing in the cortical motor system, action organization, and context-based prediction of others’ behavior during social interaction.
These findings have been presented in, so far, in 15 papers published in peer-reviewed international journals and about 12 international conference abstracts (further 3 paper are in preparation and 1 is under second round of revisions).
In sum, despite the difficulties and delays imposed by the pandemic situation, and thanks to the 6 month of extension obtained for the project, we have been able to achieve all the main scientific results in terms of data collection and we are finalizing the publication of some additional important papers the directly derive from the project activities.
Existing, interdisciplinary collaboration of the PI have been consolidated during this period; several PhD students and research fellows have been enrolled, one researchers have got a tenure-track position and other two a position as a fixed-term researchers (at Unipr and Unito). Thus, the project has strongly supported training and initial stage of career of future independent researchers.
As described above, we have been able to create and test the first environment for simultaneous wireless recording of neuronal activity and multi-camera video-behavioural tracking of freely moving monkeys, as well as to start wireless, in addition to classical head-restrained, neural recordings. We also tested and validate novel probe technologies to be applied for achieving the final goals of the project, improving the yield and quality of single neuron recordings. Furthermore, we published different papers that moved forward the existing knowledge on the anatomo-functional organization of the pre-supplementary motor area, the cortical mechanisms underlying the organization of motor actions as well as the representation and prediction of the actions of others in the primate parieto-frontal system. We completed the data aquisition phase in all the animals and are working to finalize the publication of fundamental findings such as the dynamic nature of peripersonal space coding, the organization of action planning to manipulate objects and self/other’s action representation.