BackgroundTo survive and thrive, many animals, including humans, have evolved goal-directed behaviors that can respond to specific physiological needs. An example is thirst, where the physiological need to maintain water balance drives the behavioral basic instinct to drink. Determining the neural basis of such behaviors, including thirst response, can provide insights into the way brain-wide systems transform sensory inputs into behavioral outputs. However, the neural basis underlying this spontaneous behavior remains unclear. Here, we provide a model of the neural basis of human thirst behavior.ResultsWe used fMRI, coupled with functional connectivity analysis and serial-multiple mediation analysis, we found that the physiological need for water is first detected by the median preoptic nucleus (MnPO), which then regulates the intention of drinking via serial large-scale spontaneous thought-related intrinsic network interactions that include the default mode network, salience network, and frontal-parietal control network.ConclusionsOur study demonstrates that the transformation in humans of sensory inputs for a single physiological need, such as to maintain water balance, requires large-scale intrinsic brain networks to transform this input into a spontaneous human behavioral response.