Waltmann, M. | Search bioRxiv

bioRxiv2023

Impaired updating of working memory representations in individuals with high BMI: evidence for dopaminergic mechanisms

Everyday life requires an adaptive balance between distraction-resistant maintenance of information and the flexibility to update this information when needed. These opposing mechanisms are proposed to be balanced through a working memory gating mechanism. Prior research indicates that obesity may elevate the risk of working memory deficits, yet the underlying mechanisms remain elusive. Dopaminergic alterations have emerged as a potential mediator. However, current models suggest these alterations should only shift the balance in working memory tasks, not produce overall deficits. The empirical support for this notion is currently lacking, however. To address this gap, we pooled data from three studies (N = 320) where participants performed a working memory gating task. Higher BMI was associated with overall poorer working memory, irrespective of whether there was a need to maintain or update information. However, when participants, in addition to BMI level, were categorized based on certain putative dopamine-signaling characteristics (Single Nucleotide Polymorphisms; specifically, Taq1A and DARPP-32), distinct working memory gating effects emerged. These SNPs, primarily associated with striatal dopamine transmission, appear to be linked with differences in updating, specifically, among high-BMI individuals. Moreover, blood amino acid ratio, which indicates central dopamine synthesis capacity, combined with BMI, shifted the balance between distractor-resistant maintenance and updating. These findings suggest that both dopamine-dependent and dopamine-independent cognitive effects exist in obesity. Understanding these effects is crucial if we aim to modify maladaptive cognitive profiles in individuals with obesity.

neuroscience↗

bioRxiv2022

Cortical grey matter mediates increases in model-based control and learning from positive feedback from adolescence to adulthood

Adolescents undergo maturation in cognition and brain structure. Model-based (MB) control is known to increase from childhood to young adulthood, which is mediated by cognitive abilities. Here, we asked two questions unaddressed in previous developmental studies: Firstly, what are the brain structural correlates of age-related increases in MB control? Secondly, how are age-related increases in MB control from adolescence to adulthood influenced by motivational context? A developmental sample (n=103, age: 12-42) completed structural MRI and an established task to capture MB control. The task was modified with respect to outcome valence by including (1) reward and punishment blocks to manipulate the motivational context and (2) an additional choice test to assess learning from positive vs. negative feedback. After replicating that an age-dependent increase in MB control is mediated by cognitive abilities, we demonstrate first-time evidence that grey matter density (GMD) in the parietal cortex mediates the increase of MB control with age. While motivational context did not relate to age-related changes in MB control, learning from positive feedback improved with age. Meanwhile, negative feedback learning showed no age effects. We present a first report that an age-related increase in learning from positive feedback was mediated by reduced GMD in the parietal, medial and dorsolateral prefrontal cortex. Our findings indicate that efficient brain maturation, as putatively reflected in lower GMD, in distinct and partially overlapping brain regions is a key developmental step towards age-related increases in planning and value-based choice. Significance StatementAdolescents undergo extensive maturation in cognition and brain structure. Interestingly, model-based decision-making is also known to increase from childhood to adulthood. Here, we demonstrate for the first time that grey matter density in the parietal cortex mediates an age-dependent increase in model-based control. An age-related increase in positive feedback learning was mediated by reduced grey matter density in the parietal, medial and dorsolateral prefrontal cortex. Interestingly, a manipulation of motivational context (gain reward vs. avoid punishment) did not impact age-related changes in model-based control. These findings highlight that efficient brain maturation in distinct and overlapping cortical brain regions constitutes a key developmental step towards increases in model-based planning and value-based choice.

neuroscience↗