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Our ERC funded project aims at pioneering focused ultrasounds as a new non-invasive deep brain stimulation for a causal investigation of empathy related brain processes in moral learning and decision making

As the COVID time clearly reminded us, our life is a constant trade-off between the benefits and costs for self and those of others (e.g. wearing a mask might be uncomfortable for me but might help reducing the spread of the virus to others. Shall I thus wear it (privileging the benefits for others) or not (privileging my own comfort). In order to decide what action to take, we need to be able to attribute values to every option at stake.

Reinforcement learning theory formalizes the way people learn action-outcome values: our brain associates an action with its outcome. The way we feel during the outcome will determine the value for that action. If the same action

 is repeated over time and the outcome that follows reproduces we would reinforce the initial value, if on the other hand the action results in different outcomes, we will update the initial value associated with that action to match the new state. The link between the action, its outcome and the way that we feel is relatively direct when the outcome directly affects us. For instance we know whether we feel rewarded or not when asked to work from home. Attributing a value to an action when its outcome affects someone else is less direct. It is harder for us to know whether our neighbor is happy or not to work from home.
Years of research on how we perceive other people’s states suggest we have two ways to guess how our neighbor feel. The cognitive route collects the information we have about our neighbor: whether he told us in the past he likes working from home, or whether we observed him always happily spending time outside, etc. This information will give us the option to reason about our neighbor and guess whether being at home is for them. The other, affective route, suggests that the emotional state of our neighbor, conveyed by their facial expression, posture, movements, tone of voice, etc., would resonate with the state we would feel when behaving in a similar way: for instance, when witnessing a facial expression of discontent we would activate brain regions that would be active when we are discontent, making us believe our neighbor is discontent. These two routes are not exclusive and very often are complementary.

Observations suggest that people tend to avoid situations in which they directly face people in distress more often than situation in which they are only informed about the state of the other. What is then special about witnessing what happens to others? How is our brain processing this information, and how does it differ from processing the more abstract knowledge? How does directly seeing what happens to others affect our evaluation process? Would being a direct witness make me learn faster the consequences of my actions? Would it make my choices more pro-social, when directly faced with the consequence of our choices? How consequences for myself and for others are integrated and compared in my decisions?

These questions are central to the research performed within this proposal. In order to operationalize these question in a series of scientific experiments, we developed a reinforcement learning paradigm that can be run while brain activity is recorded and perturbed. Participants are presented with two abstract symbols. They can use the mouse to click on one of them in order to reveal what consequences their choice has on the self and on another participants they have been paired to. Participants have several trials to learn which of the symbol is more often associated with higher monetary reward for self and higher physical pain for the other, and which with lower monetary reward for self and lower pain for the other. By changing the way the outcome is displayed (video of the person in pain or text indicating whether the other person is in pain or not), the gender of the pain-receiver, and action-outcome probabilities associated with each symbol we will be able to characterize the learning processes that occur during such complex decision and learning processes. By recording brain imaging data during these task we will be able to describe the circuits involved, and by using neuro-modulation methods to perturb the activity of these circuits we could understand the role each node of the circuit plays. This latter step will be fundamental in order to test the hypothesis that affective empathy is necessary to feel with the other and to update the value we associate to our own actions. Unfortunately, we know from the literature that many of the areas involved in affective empathy are difficult to non-invasively perturb, making testing causality almost impossible, leaving most of what we know about empathy lying on correlations.

This is the reason why half of the effort of the work supported by this grant focuses on the development of a new non-invasive neuro-stimulation method that would allow to perturb such deep regions. Over the past a few years, research groups have re-discovered that transcranial ultrasounds can be safely used to activate or inhibit the activity of a brain region. Differently from current neurostimulation methos, ultrasound can be focused and therefore used to selectively interfere with the activity of any region of interest, independently from their location. As the mechanisms of action of focus ultrasounds is still relatively unknown, within this grant, rodent work will investigate the mechanisms of actions of ultrasounds and their potential use as regular neurostimulation tool. Calcium imaging is combined with immuno-histology to visualize and characterize activated cells. This research line will hopefully give us a tool to establish the causal link between empathy-related phenomena and our altruistic or antisocial behavior in humans. Finally, the effect of ultrasounds, will also be measured by ultrasound imaging, which relies on changes in blood flow, more directly comparable with what normally people measure in human participants with fMRI.

Do you wish to participate in one of the experiment from the lab? Please, drop an email to: [email protected]