Corticocortical and Thalamocortical Changes in Functional Connectivity and White Matter Structural Integrity after Reward-Guided Learning of Visuospatial Discriminations in Rhesus Monkeys.

The frontal cortex and temporal lobes together regulate complex learning and memory capabilities. Here, we collected resting-state functional and diffusion-weighted MRI data before and after male rhesus macaque monkeys received extensive training to learn novel visuospatial discriminations (reward-guided learning). We found functional connectivity changes in orbitofrontal, ventromedial prefrontal, inferotemporal, entorhinal, retrosplenial, and anterior cingulate cortices, the subicular complex, and the dorsal, medial thalamus. These corticocortical and thalamocortical changes in functional connectivity were accompanied by related white matter structural alterations in the uncinate fasciculus, fornix, and ventral prefrontal tract: tracts that connect (sub)cortical networks and are implicated in learning and memory processes in monkeys and humans. After the well-trained monkeys received fornix transection, they were impaired in learning new visuospatial discriminations. In addition, the functional connectivity profile that was observed after the training was altered. These changes were accompanied by white matter changes in the ventral prefrontal tract, although the integrity of the uncinate fasciculus remained unchanged. Our experiments highlight the importance of different communication relayed among corticocortical and thalamocortical circuitry for the ability to learn new visuospatial associations (learning-to-learn) and to make reward-guided decisions.SIGNIFICANCE STATEMENT Frontal neural networks and the temporal lobes contribute to reward-guided learning in mammals. Here, we provide novel insight by showing that specific corticocortical and thalamocortical functional connectivity is altered after rhesus monkeys received extensive training to learn novel visuospatial discriminations. Contiguous white matter fiber pathways linking these gray matter structures, namely, the uncinate fasciculus, fornix, and ventral prefrontal tract, showed structural changes after completing training in the visuospatial task. Additionally, different patterns of functional and structural connectivity are reported after removal of subcortical connections within the extended hippocampal system, via fornix transection. These results highlight the importance of both corticocortical and thalamocortical interactions in reward-guided learning in the normal brain and identify brain structures important for memory capabilities after injury.