Activation of different anterior cingulate foci in association with hypothesis testing and response selection.

Much everyday behavior is implicitly guided by hypotheses about the world which are monitored and updated in the light of changing circumstances. The process of translating these hypotheses into behavior typically involves implementing choices, often based on incompletely specified information. The present study aimed at modeling these processes to determine the neural substrates of hypothesis testing and, in particular, how these are modulated by the requirement to make choices. We used positron emission tomography to study six right-handed volunteers performing an insoluble hypothesis testing task in which subjects attempted to identify a rule determining which of two black and white checkerboard stimuli was correct. This task was compared with a control task matched for perceptuomotor requirements, but involving no hypothesis testing. Both tasks were performed with or without a requirement to make a choice. Structures activated in association with hypothesis testing included the cerebellum, left anterior cingulate, right precuneus, right thalamus, and left inferior frontal gyrus. The requirement to choose a response was associated with activation of the left anterior cingulate and right lateral orbitofrontal cortex. A significant modulation of activation associated with hypothesis testing was observed in the anterior cingulate region that was also activated by making a choice. These findings are discussed in terms of the neural substrates of complex "executive" tasks. We argue that the precise cognitive parameters of such tasks, and specifically the requirement to implement decisions in actual behavior, are critical in determining the associated neural response.