Bäuchl, C. | bioRxiv Science

bioRxiv2026

Reduced Control Over Pavlovian-to-Instrumental Transfer in Human Addiction: A Systematic Investigation Across Alcohol Use Disorder and Smoking Status

Pavlovian conditioned stimuli can compromise goal-directed behavior, particularly when they conflict with the required instrumental response. Previous research linked an increased impact of such Pavlovian-to-instrumental transfer (PIT) interference to risky drinking and alcohol dependence. However, it remained unclear whether the observed behavioral and neural alterations generalize to the substantially larger population of non-treatment-seeking individuals with predominantly mild-to-moderate alcohol use disorder (AUD) and to other substances like nicotine. We therefore studied 200 participants from the general population who were stratified by AUD and smoking status before completing a single-lever PIT task during functional imaging. PIT interference was measured as the difference in error rates between incongruent PIT trials, characterized by conflicts of Pavlovian and instrumental stimuli, and congruent trials. Associations with AUD and smoking status, as well as dimensional associations of behavioral PIT interference and neural responses to PIT conflicts with substance-related measures, were examined. As expected, participants with AUD showed greater PIT interference and reduced conflict-related activation in the lateral prefrontal, dorsomedial prefrontal, and anterior cingulate cortex than participants without AUD. The magnitude of these alterations also correlated with higher AUD severity and alcohol consumption, while being independent of smoking status and other smoking-related measures. These findings suggest that enhanced PIT interference generalizes to the broader AUD population but may not extend to other substances like nicotine. They further implicate a reduced recruitment of prefrontal control networks during PIT conflicts as a potential mechanism underlying enhanced PIT interference in AUD and its association with clinically relevant outcome measures.

neuroscience↗

bioRxiv2021

L-DOPA enhances hippocampal directionsignals in younger and older adults

Previous studies indicate a role of dopamine in hippocampus-dependent spatial navigation. Although neural representations of direction are an important aspect of spatial cognition, it is not well understood whether dopamine directly affects these representations, or only impacts other aspects of spatial brain function. Moreover, both dopamine and spatial cognition decline sharply during age, raising the question which effect dopamine has on directional signals in the brain of older adults. To investigate these questions, we used a double-blind cross-over L-DOPA/Placebo intervention design in which 43 younger and 37 older adults navigated in a virtual spatial environment while undergoing functional magnetic resonance imaging (fMRI). We studied the effect of L-DOPA, a DA precursor, on fMRI activation patterns that encode spatial walking directions that have previously been shown to lose specificity with age. This was done in predefined regions of interest, including the early visual cortex, retrosplenial cortex, and hippocampus. Classification of brain activation patterns associated with different walking directions was improved in the hippocampus and the retrosplenial cortex following L-DOPA administration. This suggests that DA enhances the specificity of neural representations of walking direction in these areas. In the hippocampus these results were found in both age groups, while in the RSC they were only observed in younger adults. Taken together, our study provides evidence for a mechanistic link between DA and the specificity of neural responses during spatial navigation. Significance StatementThe sense of direction is an important aspect of spatial navigation, and neural representations of direction can be found throughout a large network of space-related brain regions. But what influences how well these representations track someones true direction? Using a double-blind cross-over L-DOPA/Placebo intervention design, we find causal evidence that the neurotransmitter dopamine impacts the fidelity of direction selective neural representations in the human hippocampus and retrosplenial cortex. Interestingly, the effect of L-DOPA was either equally present or even smaller in older adults, despite the well-known age related decline of dopamine. These results provide novel insights into how dopamine shapes the neural representations that underlie spatial navigation.

neuroscience↗