A neurometabolic mechanism involving dmPFC/dACC lactate in physical effort-based decision-making

Motivation levels vary across individuals, yet the underlying mechanisms driving these differences remain elusive. The dorsomedial prefrontal cortex/dorsal anterior cingulate cortex (dmPFC/dACC) and the anterior insula (aIns) play crucial roles in effort-based decision-making. Here, we investigate the influence of lactate, a key metabolite involved in energy metabolism and signaling, on decisions involving both physical and mental effort, as well as its effects on neural activation. Using proton magnetic resonance spectroscopy and functional MRI in 63 participants, we find that higher lactate levels in the dmPFC/dACC are associated with reduced motivation for physical effort, a relationship mediated by neural activity within this region. Additionally, plasma and dmPFC/dACC lactate levels correlate, suggesting a systemic influence on brain metabolism. Supported by path analysis, our results highlight lactate's role as a modulator of dmPFC/dACC activity, hinting at a neurometabolic mechanism that integrates both peripheral and central metabolic states with brain function in effort-based decision-making.