Manuck, S. B. | Search bioRxiv

bioRxiv2025

Community Socioeconomic Disadvantage relates to White Matter Hyperintensity Burden in Mid-to-Late Life Adults

BackgroundResiding in communities characterized by socioeconomic disadvantage may confer risk for neurodegenerative brain changes and future neuropathology. Based on prior evidence, this study tested the hypotheses that (1) community-level disadvantage would relate independently of individual-level socioeconomic position to white matter hyperintensities (WMHs), which reflect subclinical brain pathology that may presage later dementia; and (2) this association would be partly explained by blood pressure, cardiometabolic risk, and/or systemic levels of inflammation. These hypotheses were examined among otherwise healthy middle- and older-aged adults without clinical dementia at testing. MethodsParticipants were 388 adults aged 40-72 years (53% female; 12% non-White) whose street addresses were entered into the Neighborhood Atlas to compute Area Deprivation Index scores by census block. Participants also underwent high resolution (7 Tesla) brain imaging to assess total WMH volume normalized for intracranial volume, and assessment of blood pressure, cardiometabolic (adiposity, lipids, glucose and insulin), and inflammatory (interleukin-6 and C-reactive protein) risk factors. ResultsLinear regression models showed that higher community deprivation on the ADI associated with greater WMH volume, independently of age, sex, years of education and smoking. This association was largely independent of blood pressure, cardiometabolic risk and systemic inflammation. ConclusionThe present novel findings add to growing evidence that community disadvantage relates to preclinical neurodegenerative changes, which may contribute to accelerated brain and cognitive aging. Future work is warranted to better understand pathways that link residential environments to brain health and to identify targets for community and public policy interventions.

neuroscience↗

bioRxiv2022

D2 dopamine receptor expression, sensitivity to rewards, and reinforcement learning in a complex value-based decision-making task

In the basal ganglia, different dopamine subtypes have opposing dynamics at post-synaptic receptors, with the ratio of D1 to D2 receptors determining the relative sensitivity to gains and losses, respectively, during value-based learning. This effective sensitivity to reward feedback interacts with phasic dopamine levels to determine the effectiveness of learning, particularly in dynamic feedback situations where frequency and magnitude of rewards need to be integrated over time to make optimal decisions. Using both simulations and behavioral data in humans, we evaluated how reduced sensitivity to losses, relative to gains, leads to suboptimal learning in the Iowa Gambling Task (IGT), a complex value-learning task. In the behavioral data, we tested individuals with a variant of the human dopamine receptor D2 (DRD2; -141C Ins/Del and Del/Del) gene that associates with lower levels of D2 receptor expression (N=119) and compared their performance to non-carrier controls (N=319). The magnitude of the reward response was measured by looking at ventral striatal (VS) reactivity to rewards in the Cards task using fMRI. DRD2 variant carriers had generally lower performance in the IGT than non-carriers, consistent with reduced sensitivity to losses. There was also a positive association between VS reactivity and performance in the IGT, however, we found no statistically significant difference in this effect between DRD2 carriers and non-carriers. Thus, while reduced D2 receptor expression was associated with less efficient learning in the IGT, we did not find evidence for the moderation of this effect by the magnitude of the reward response.

neuroscience↗