Mesial prefrontal cortex and alcohol misuse: dissociating cross-sectional and longitudinal relationships in UK Biobank

Abstract

Background: Alcohol misuse is a major global public health issue. The disorder is characterized by aberrant neural networks interacting with environment and genetics. Dissecting the neural substrates and functional networks that relate to longitudinal changes in alcohol use from those that relate to alcohol misuse cross-sectionally is important to elucidate therapeutic approaches.

Methods: To assess how neuroimaging data, including T1, resting-state fMRI, and diffusion-weighted imaging, relate to alcohol misuse cross-sectionally and longitudinally in UK Biobank, the present study analyzed the population-based normative sample with range of alcohol misuse, ages 45 to 81 years old with 24,784 participants in cross-sectional analysis and 3,070 in longitudinal analysis 2 years later.

Results: Cross-sectional analysis shows alcohol use is associated with a reduction in dorsal anterior cingulate cortex (dACC) and dorsomedial prefrontal (dmPFC) grey matter concentration and functional resting-state connectivity (nodal degree: T=-12.99, p<10^- 17). Reduced dACC/dmPFC functional connections to the ventrolateral prefrontal, amygdala, striatum relate to greater alcohol use. In longitudinal analysis, higher resting- state nodal degree (T=-3.27, p=0.0011) and T1 grey matter concentration in the ventromedial prefrontal (vmPFC) cortex relate to reduced alcohol intake frequency 2 years later. Higher vmPFC and frontal-parietal executive network functional connectivity associate with lower subsequent drinking longitudinally.

Conclusion: Dorsal versus ventromedial prefrontal regions are differentially related to alcohol misuse cross-sectionally or longitudinally in a large UK Biobank normative dataset. Our study provides a comprehensive understanding of the neurobiological substrates of alcohol use as a state or prospectively, thereby providing potential targets for clinical treatment.