• dissociated prefrontal activation;
  • visual working memory;
  • subthalamic stimulation;
  • Parkinson's disease;
  • PET

In this study, we investigated the neural substrates involved in visual working memory (WM) and the resulting effects of subthalamic nucleus (STN) stimulation in Parkinson's disease (PD). Cerebral activation revealed by positron emission tomography was compared among Parkinson patients with (PD-ON) or without (PD-OFF) STN stimulation, and a group of control subjects (CT) in two visual WM tasks with spatial (SP) and nonspatial (NSP) components. PD-OFF patients displayed significant reaction time (RT) deficits for both memory tasks. Although there were no significant differences in RT between patients with PD-ON and -OFF stimulation, patients with PD-ON stimulation performed comparably to controls. The memory tasks were executed with normal error rates in PD-ON and -OFF stimulation. In contrast to these behavioral results, whether the corresponding prefrontal activation was differentially affected by deep brain stimulation status in patients depended on whether the WM modality was SP versus NSP. Thus, SP WM was associated with (1) abnormal reduction in dorsolateral prefrontal activity in PD-OFF and -ON stimulation and (2) abnormal overactivation in parieto-temporal cortex in PD-OFF and in limbic circuits in PD-ON stimulation. In NSP WM, normal activation of the ventral prefrontal cortex was restored in PD-ON stimulation. In both visual modalities the posterior cerebral regions including fusiform cortex and cerebellum, displayed abnormally reduced activity in PD. These results indicate that PD induces a prefrontal hypoactivation that STN stimulation can partially restore in a modality selective manner by additional recruitment of limbic structures in SP WM or by recovery of the ventral prefrontal activation in NSP WM. Hum Brain Mapp 35:552–566, 2014. © 2012 Wiley Periodicals, Inc.