Identifying Mediodorsal Thalamus-Frontal Cortex Partnering in Flexible Cognition
1 Mar 2026 - 1 Mar 2029
To provide a more precise and translationally relevant understanding of the MD’s contribution to cognitive flexibility and propose potential treatment options to restore cognitive flexibility when it has been lost. This could help to better support and improve the quality of life of New Zealanders with cognitive decline, mental health disorders, or neurodevelopmental conditions because of poor MD-PFC thalamic functioning. The proposed research addresses four critical gaps in current understanding of cognitive flexibility. First, it will clarify the role of the MD in supporting adaptive decision-making, where the current behaviour is no longer optimal and must be altered. Second, it will overcome a limitation of traditional animal tasks by employing our novel decision-making task that requires integration of both reward magnitude and probability of reward—closely mirroring human decision-making. Third, it will examine the roles of two neurotransmitters, serotonin and dopamine in cognitive flexibility. Finally, it will examine whether cognitive flexibility can be pharmacologically restored after permanent damage to MD neurons by administering low doses of methamphetamine and amphetamine, which enhance dopaminergic and serotonergic signalling.
