Aim of this study is to visualize the neural correlate of executive functions. In rodents, operant learning is a suitable task to evaluate cognitive functions, including attention, impulsivity, set-shifting and decision making. To this end, we developed a non-magnetic operant learning task chamber. A fMRI Mice (C57BL/6 or Alzheimer’s Disease (AD) model mice APP/PS1) attached with head-post were habituated to the operant chamber for 3 days, performed Go task for 7 days, and were switched to No-Go task. To visualize the neural activity during operant learning (Go task or No-Go task), we utilized Spin Echo EPI, instead of Gradient Echo EPI, due to the resistance to field inhomogeneity at ultra-high field. We acquired series of data from were divided into the correct and the error trials, and were processed by SPM12 attached with SPMmouse. We plotted the activation areas from behaving mouse brain by the two-sample t-test between the correct and the error trials. During Go-task, we detected the BOLD elevation of brain areas including the visual cortex, the hippocampus, and the superior colliculus (FWE, P<0.05). After the switching to No-Go task (operant reversal learning), we detected the BOLD activation of the prefrontal cortices, including the medial frontal and the lateral, as well as the orbit of frontal division of the mouse prefrontal cortex from wild type mice when performing the correct trials.

On the contrary, in Alzheimer’s model mice, we observed the BOLD activation of the prefrontal cortex in the error trials and detected severe decline in performing the No-Go task, which may relate to the dysregulation of prefrontal executive system in AD mice, probably due to neuroinflammation accompanied with amyloid pathology. BOLD fMRI imaging at ultra-high field enables us to visualize the neural activity at the high spatio-temporal resolution. Mouse task fMRI during operant learning at ultra-high field will offer unexperienced data to basic as well as clinical research fields.