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.

Mapping the anatomy of perceptual pseudoneglect. A multivariate approach.

Fundamental to the understanding of the functions of spatial cognition and attention is to clarify the underlying neural mechanisms. It is clear that relatively right-dominant activity in ventral and dorsal parieto-frontal cortex is associated with attentional reorienting, certain forms of mental imagery and spatial working memory for higher loads, while lesions mostly to right ventral areas cause spatial neglect with pathological attentional biases to the right side. In contrast, complementary leftward biases in healthy people, called pseudoneglect, have been associated with varying patterns of cortical activity. Notably, this inconsistency may be explained, at least in part, by the fact that pseudoneglect studies have often employed experimental paradigms that do not control sufficiently for cognitive processes unrelated to pseudoneglect. To address this issue, here we administered a carefully designed continuum of pseudoneglect and control tasks in healthy adults while using functional magnetic resonance imaging (fMRI). Data submitted to partial least square (PLS) imaging analysis yielded a significant latent variable that identified a right-dominant network of brain regions along the intra-occipital and -parietal sulci, frontal eye fields and right ventral cortex in association with perceptual pseudoneglect. Our results shed new light on the interplay of attentional and cognitive systems in pseudoneglect.

Can complex visual discrimination deficits in amnesia be attributed to the medial temporal lobe? An investigation into the effects of medial temporal lobe damage on brain connectivity.

It has been suggested that complex visual discrimination deficits in patients with medial temporal lobe (MTL) damage may be explained by damage or dysfunction beyond the MTL. We examined the resting functional networks and white matter connectivity of two amnesic patients who have consistently demonstrated discrimination impairments for complex object and/or spatial stimuli across a number of studies. Although exploratory analyses revealed some significant differences in comparison with neurologically healthy controls (more specifically in the patient with a larger MTL lesion), there were no obvious findings involving posterior occipital or posterior temporal regions, which can account entirely for their discrimination deficits. These findings converge with previous work to support the suggestion that the MTL does not subserve long-term declarative memory exclusively.