Thalamostriatal Interactions in Human Reversal Learning

Cognitive flexibility, the ability to flexibly update thought and behaviour, is a crucial component of adaptation and survival, and it is disrupted in neuropsychiatric disorders and psychopathology. Reversal learning tasks are often used to investigate cognitive flexibility. Human studies of reversal learning typically focus on neural mechanisms required to identify changes in response contingencies, rather than on mechanisms required to learn and express a new response. However, animal studies of reversal learning have shown a key and specific role in this process for the dorsal striatum and its interactions with the centromedian parafascicular (CM-Pf) thalamus, but this system is not as well understood in humans. The aim of this study was to investigate the role of the human dorsal striatum and its interactions with the thalamus during probabilistic reversal learning, specifically with respect to learning a new response strategy. We used psychophysiological interaction (PPI) analysis of functional magnetic resonance imaging (fMRI) data, to measure task-dependent changes in connectivity between striatal and thalamic functional subdivisions. We show that connectivity between the dorsal striatum and the centromedian parafascicular (CM-Pf) thalamic complex was increased during reversal, but not initial, learning. The strength of this connectivity was associated with the ability to flexibly alter behaviour. This study helps to bridge the gap between animal studies of this system, and human studies of reversal learning and cognitive flexibility more generally.