The prefrontal cortex (PFC) is an area of the brain which controls many higher-level functions including decision making. Much research has been carried out on the function of PFC subregions but much of it is disparate due to the wide range of techniques and species used. There were two main aims of this thesis. First, I proposed to investigate the connections and functions of the PFC and related regions, and the role of some ofthese in effort-based decision making. Second, I hoped to use complementary techniques to compare across humans, monkeys and rats, and to combine my findings to increase our understanding of decision making. I used diffusion-weighted imaging to investigate the connections of PFC regions with other brain areas, and compared the results in humans and monkeys. The connections of each PFC region had a unique pattern which was similar between the species, indicating how each region may function. I then carried out a detailed study investigating the role of one PFC subregion, the medial frontal cortex (MFC), and its interactions with the dopaminergic midbrain in effort-based decision making, as we do not fully know how such regions interact with the rest of the brain when making decisions. I showed the MFC had a particular cognitive role in decision ml;lking with respect to the location of a reward-guided action. Finally I studied effort-based responding in the human brain using functional magnetic resonance imaging. This study revealed a network of regions involved in acting for a reward, and that the anterior cingulate cortex (ACC) may have a role in integrating factors which constitute the value of an action. Overall my results suggest that the MFC and ACC have specific roles in effort-based decision making, which can be further understood by comparing their connections with those ofother PFC regions.