Functional Imaging of Subthalamic Nucleus Deep Brain Stimulation in Parkinson’s Disease Tessel Boertien, 1,2 Ludvic Zrinzo, MD, FRCS, 1,3 Joshua Kahan, 1 Marjan Jahanshahi, PhD, 1 Marwan Hariz, MD, PhD, 1,3 Laura Mancini, PhD, 4,5,6 Patricia Limousin, MD, PhD, 1 and Thomas Foltynie, MRCP, PhD 1 * 1 Unit of Functional Neurosurgery, UCL Institute of Neurology, Queen Square, London, United Kingdom 2 Faculty of Medicine, University of Amsterdam, Amsterdam, The Netherlands 3 Victor Horsley Department of Neurosurgery, National Hospital for Neurology & Neurosurgery, Queen Square, London, United Kingdom 4 Lysholm Department of Neuroradiology, National Hospital for Neurology & Neurosurgery, UCLH NHS Foundation Trust, Queen Square, London, United Kingdom 5 Academic Neuroradiological Unit, Department of Brain Repair and Rehabilitation, UCL Institute of Neurology, Queen Square, London, United Kingdom 6 Queen Square Imaging Centre, Queen Square, London, United Kingdom ABSTRACT: Deep brain stimulation of the subtha- lamic nucleus is an accepted treatment for the motor complications of Parkinson’s disease. The therapeutic mechanism of action remains incompletely understood. Although the results of deep brain stimulation are similar to the results that can be obtained by lesional surgery, accumulating evidence from functional imaging and clini- cal neurophysiology suggests that the effects of subtha- lamic nucleus-deep brain stimulation are not simply the result of inhibition of subthalamic nucleus activity. Posi- tron emission tomography/single-photon emission com- puted tomography has consistently demonstrated changes in cortical activation in response to subthalamic nucleus-deep brain stimulation. However, the technique has limited spatial and temporal resolution, and therefore the changes in activity of subcortical projection sites of the subthalamic nucleus (such as the globus pallidus, substantia nigra, and thalamus) are not as clear. Clarify- ing whether clinically relevant effects from subthalamic nucleus-deep brain stimulation in humans are mediated through inhibition or excitation of orthodromic or anti- dromic pathways (or both) would contribute to our understanding of the precise mechanism of action of deep brain stimulation and may allow improvements in safety and efficacy of the technique. In this review we discuss the published evidence from functional imaging studies of patients with subthalamic nucleus-deep brain stimulation to date, together with how these data inform the mechanism of action of deep brain stimulation. V C 2011 Movement Disorder Society Key Words: Parkinson’s disease; functional imaging; functional magnetic resonance imaging; deep brain stimulation; subthalamic nucleus Deep brain stimulation (DBS) of the subthalamic nu- cleus (STN) can lead to significant improvements of tremor, rigidity, and bradykinesia in patients with advanced Parkinson’s disease (PD) inadequately con- trolled by medical therapies. A mean improvement of 50%–60% is observed in the motor scores of the Uni- fied Parkinson’s Disease Rating Scale, (UPDRS) part III, and levodopa requirements are also reduced on av- erage by 50%–60%. 1–4 Quality of life has been shown to improve greatly after surgery in patients younger than 65 years. 5–7 Specific side effects of STN-DBS include dysarthria and/or hypophonia, reduction in verbal fluency, and neuropsychiatric side effects. 3,8–10 How STN-DBS changes brain activity leading to therapeutic and/or unwanted effects in PD remains unclear. The functional deafferentation model of basal ganglia function 11 would suggest that high-frequency STN-DBS reduces the excitatory influence of the STN on the GPi, resulting in a reduction in the downstream ------------------------------------------------------------ *Correspondence to: Dr. Thomas Foltynie, Box 146, National Hospital for Neurology & Neurosurgery, Queen Square, London, WC1N 3BG, UK; T.Foltynie@ion.ucl.ac.uk Funding agencies: This work was undertaken at UCL/UCLH and was partly funded by the Department of Health NIHR Biomedical Research Centres funding scheme. The Unit of Functional Neurosurgery, Queen Square, London, is supported by the Parkinson’s Appeal. Relevant conflicts of interest/financial disclosures: Nothing to report. Full financial disclosures and author roles may be found in the online version of this article. Received: 17 November 2010; Revised: 7 April 2011; Accepted: 17 April 2011 Published online 14 June 2011 in Wiley Online Library (wileyonlinelibrary.com). DOI: 10.1002/mds.23788 REVIEW Movement Disorders, Vol. 26, No. 10, 2011 1835