Report

Teaser, summary, work performed and final results

Periodic Reporting for period 2 - WIRELESS (Motor and cognitive functions of the monkey premotor cortex during free social interactions)

Teaser

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...

Summary

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. This has strongly limited the range of behaviors that can be explored, the variety of questions that can be addressed, and the ecological relevance of the discoveries. Indeed, 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 recording of neuronal activity, the development of new systems for video behavioral monitoring, and the synchronization of multiple sources of data in order to be able to study the relationship between brain functioning and behavior in freely-moving subjects. Therefore, there are sufficient technological resources to be exploited for moving forward neurophysiology to tackle 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 by studying contexts and behaviors previously impossible to investigate with conventional techniques.

Work performed

In the first 30 months of the project 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. Since now, two pairs of macaque monkeys, normally housed together (one dominant and one subordinate), have been prepared for state-of-the-art laboratory sessions and then individually trained to 1) perform a set of classical visuomotor tasks in head-restrained situations and 2) enter in the NER, with positive reinforcement techniques (one of the pairs is undergoing a training to perform a more complex and novel “social interaction task”). 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. This new setup will make possible the study of a large variety of ethologically relevant behaviors in the NHPs’ repertoire (which were impossible to investigate with conventional methods) during simultaneous neural recording.
In parallel, we also performed neural recordings with innovative neural probes in state-of-the-art laboratory conditions. These studies yielded important technical validation data for innovative multi-site recording and stimulation devices, which will be exploited for wirelessly recording of neuronal activity during unconstrained behavior in the NER. Furthermore, these studies produced novel data on 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 5 papers published in peer-reviewed international journals and 3 international conference abstracts. For example, in a recent paper published in the Proceedings of the National Academy of Science (PNAS) of the United States, we demonstrated the existence, in the presupplementary motor area, of a novel “object mirroring mechanism”, hypothesized in the project, by which an observer can predict what another will do when facing an object in a specific context by recruiting the same neurons he/she would activate to decide what to do when facing the same context. Two additional papers are currently under revisions and 5 abstracts have been submitted for the next Society for Neuroscience meeting.
In sum, we have created the preconditions for starting wireless recording in the next weeks, and we achieved most of the scientific and technical goals expected for the first 30 months of the project, as demonstrated by the papers published so far and by those currently under revision.
Existing, interdisciplinary collaboration of the PI have been consolidated during the first half of the project, in the context of which 3 new PhD students in Neuroscience have been enrolled and are currently working at the project, in addition to 3 post-docs: among these latter, one has got a tenure-track position at the University of Parma and another one a position as a fixed-term researcher within the ERC project. Thus, the project is supporting training and initial stage of career of future researchers.

Final results

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. 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.
Before the end of the project, we expect to directly cross-validate the unconstrained wireless recording methodology in freely-behaving monkeys by comparing the results with those achieved in state-of-the-art laboratory settings. We also expect to be able to provide novel data from unconstrained wireless recording sessions regarding the dynamic nature of peripersonal space, manipulable objects coding and self/other’s action representation, exploring a range of phenomena and settings previously impossible to scrutinize in constrained laboratory conditions.

Website & more info

More info: https://www.unipr.it/node/16979.