Séminaire Pierre VASSILIADIS

A crucial function of the striatum is the ability to incentivize behavior based on reward. Yet, because of its deep localization in the brain, it has so far not been possible to investigate the causal role of the striatum in reward processing non-invasively during healthy behavior. Here, we leveraged a new non-invasive brain stimulation technology, namely transcranial temporal interference stimulation (tTIS, Grossman et al., 2017; Wessel et al. 2023, Nat Neurosci) to target the striatum during reinforcement learning of a motor skill. In this randomized, sham-controlled, double-blind study, we applied tTIS while 24 participants were practicing a force-tracking task with or without real-time reward feedback and with concurrent functional magnetic resonance imaging (fMRI). Based on previous studies showing reinforcement-dependent, time-locked bursts of high gamma striatal activity following reward delivery (Berke 2009, EJN), we compared the behavioral and neurophysiological effects of 80Hz tTIS (tTIS80Hz) with those of 20Hz tTIS (TIS20Hz) and sham stimulation (tTISsham). More specifically, we hypothesized that applying a constant, open-loop high gamma rhythm in the striatum would disturb the temporally precise and reinforcement-specific modulation of high gamma activity in the striatum and perturb reinforcement motor learning. As expected, participants learned more when reinforcement was provided in tTISsham. Consistent with our hypothesis, these benefits were abolished by tTIS80Hz, but not by tTIS20Hz. Moreover, in line with a role of striatal beta oscillations in motor function, motor learning without reinforcement was reduced with tTIS20Hz, but not with tTIS80Hz. We also find that the impairment of reinforcement-related benefits in motor learning with tTIS80Hz was associated to individual changes of neural activity in the putamen and caudate nucleus, suggesting that the observed behavioral effects were indeed related to neuromodulation of striatal activity. By combining these data with other studies employing tTIS (total of >250 sessions), we further show that the stimulation is safe, generally perceived as “mild” and compatible with efficient blinding. Finally, we will show how the technology can be applied in other forms of motivated behavior such as in the context of effort-based decision-making for reward. Put together, our work suggests that striatal tTIS is a promising tool to investigate fundamental mechanisms of motivated behavior paving the way for their modulation in populations of patients affected by disorders of motivation.