1. ¹Functional Neurosurgery Unit, Sobell Department of Motor Neuroscience and Movement Disorders, Institute of Neurology, London, UK
2. ²Hammersmith Imanet, MRC Clinical Sciences Centre, Faculty of Medicine, Imperial College, Hammersmith Hospital, London, UK

Correspondence: Professor M Jahanshahi, Functional Neurosurgery Unit, Sobell Department of Motor Neuroscience and Movement Disorders, Institute of Neurology, 8/11 Queen Square, WC1N 3BG London, UK. E-mail: m.jahanshahi@ion.ucl.ac.uk

Received 21 August 2006; Revised 15 September 2006; Accepted 3 October 2006; Published online 22 November 2006.

Abstract

To investigate the effects of bilateral subthalamic nucleus (STN) stimulation on patterns of brain activation during random number generation (RNG), a task that requires suppression of habitual counting and response selection under competition. We used H₂¹⁵O positron emission tomography to investigate the changes of regional cerebral blood flow (rCBF) induced by bilateral STN stimulation during a RNG task, in six patients with Parkinson's disease. Paced RNG at 1 Hz was compared with a control counting task. Both tasks were performed off medication with deep brain stimulation on and off. Subthalamic nucleus stimulation had a negative effect on performance of fast-paced RNG, leading to reduced randomness and increased habitual counting. Subthalamic nucleus stimulation also induced a reduction of rCBF in the left dorsal frontal gyrus, inferior frontal gyrus, dorsolateral prefrontal cortex, posterior and right anterior cingulate, and an increase of rCBF in the right internal globus pallidum (GPi) during RNG. Stimulation of the STN significantly altered pallidal coupling with frontal and temporal areas compared with when the stimulators were off. In conclusion, during RNG: (i) STN stimulation activates its output neurons to the GPi; (ii) STN stimulation induces increased inhibition of a prefrontal–cingulate network. This is the first direct evidence that STN stimulation significantly alters pallidal coupling with prefrontal, cingulate, and temporal cortices during performance of a task that requires response selection under competition.