A small almond-shaped structure deep in the brain, the mediodorsal thalamus, acts as a relay station that shuttles messages between different cortical regions, but no one knows exactly which messages it carries or how they shape learning and decision-making. This matters because the same brain region is consistently disrupted in schizophrenia, ADHD, and other neuropsychiatric disorders. Researchers know the mediodorsal thalamus is involved, but they do not understand the fundamental rules of how it communicates with the cortex—what information it transmits, which cortical areas send the instructions, and how those signals influence behaviour. The team will map these circuits in primates using a combination of neuroimaging, electron microscopy, and electrophysiology, then test how disrupting the relay affects cognitive tasks. They will also scan thalamic stroke patients and healthy controls to see whether the same principles hold in humans. This is fundamental science. It will not produce a drug or a diagnostic test tomorrow. But understanding how subcortical–cortical networks actually work is a prerequisite for designing targeted therapies for conditions where those networks fail—much as knowing how a switchboard operates is necessary before you can fix a crossed line.
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Complex cognition arises in distributed and integrated brain networks. Animal models have shown the critical importance of the magnocellular subdivision of mediodorsal thalamus (MDmc) to cognitive processes via its cortical interactions. Neuroimaging of several neuropsychiatric diseases has also highlighted changes in the connectivity of MD and cortical interactions. Yet critical knowledge about how the MDmc and cortex communicate effectively in cognition remains unknown. One of the key goals of this research will determine the origins and synaptic characteristics of cortical driver inputs of MDmc (i.e. those cortical inputs that are capable of transmitting a message via the transthalamic MDmc route to other cortical areas). This goal will be achieved by combining neuroimaging, immunohistochemistry and immuno-electron microscopy in primates to understand which cortical areas relay messages via the MDmc neural networks. Further, we do not know what the messages are being relayed via the MDmc to other cortical regions and how they are important for cognition. Thus the other key goal of this research is to investigate what the messages are, relayed via the MDmc in primates using cognitive testing, electrophysiology, and discrete manipulations to MDmc and interconnected cortical regions. The overall aim of this goal is to establish how communication between the MDmc and cortex is important for learning new information and decision-making. Cross-species neuropsychological testing using primate-designed cognitive tasks and neuroimaging in thalamic stroke patients and healthy controls will provide an additional step in advancing fundamental knowledge about the critical importance of communication between subcortical-cortical integrated networks in cognition.
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