Enhanced Activation of Motor Execution Networks Using Action Observation Combined with Imagination of Lower Limb Movements Michael Villiger 1,2,3 , Natalia Este ´ vez 2 , Marie-Claude Hepp-Reymond 3 , Daniel Kiper 3 , Spyros S. Kollias 2 , Kynan Eng 3 *, Sabina Hotz-Boendermaker 1 1 Spinal Cord Injury Center, University Hospital Balgrist, Zurich, Switzerland, 2 Institute of Neuroradiology, University Hospital Zurich, Zurich, Switzerland, 3 Institute of Neuroinformatics, University of Zurich and ETH Zurich, Zurich, Switzerland Abstract The combination of first-person observation and motor imagery, i.e. first-person observation of limbs with online motor imagination, is commonly used in interactive 3D computer gaming and in some movie scenes. These scenarios are designed to induce a cognitive process in which a subject imagines himself/herself acting as the agent in the displayed movement situation. Despite the ubiquity of this type of interaction and its therapeutic potential, its relationship to passive observation and imitation during observation has not been directly studied using an interactive paradigm. In the present study we show activation resulting from observation, coupled with online imagination and with online imitation of a goal-directed lower limb movement using functional MRI (fMRI) in a mixed block/event-related design. Healthy volunteers viewed a video (first- person perspective) of a foot kicking a ball. They were instructed to observe-only the action (O), observe and simultaneously imagine performing the action (O-MI), or imitate the action (O-IMIT). We found that when O-MI was compared to O, activation was enhanced in the ventralpremotor cortex bilaterally, left inferior parietal lobule and left insula. The O-MI and O-IMIT conditions shared many activation foci in motor relevant areas as confirmed by conjunction analysis. These results show that (i) combining observation with motor imagery (O-MI) enhances activation compared to observation-only (O) in the relevant foot motor network and in regions responsible for attention, for control of goal-directed movements and for the awareness of causing an action, and (ii) it is possible to extensively activate the motor execution network using O-MI, even in the absence of overt movement. Our results may have implications for the development of novel virtual reality interactions for neurorehabilitation interventions and other applications involving training of motor tasks. Citation: Villiger M, Este ´vez N, Hepp-Reymond M-C, Kiper D, Kollias SS, et al. (2013) Enhanced Activation of Motor Execution Networks Using Action Observation Combined with Imagination of Lower Limb Movements. PLoS ONE 8(8): e72403. doi:10.1371/journal.pone.0072403 Editor: Alessio Avenanti, University of Bologna, Italy Received February 22, 2013; Accepted July 12, 2013; Published August 28, 2013 Copyright: ß 2013 Villiger et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: The work was funded by the International Foundation for Research in Paraplegia (IRP), Swiss National Science Foundation (SNF) [51NF40-144619/ PMPDP3-124282], OPO-Foundation, and the Neuroscience Center Zurich (ZNZ). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing Interests: The authors have declared that no competing interests exist. * E-mail: kynan@ini.phys.ethz.ch Introduction Over the last two decades several research groups have published data lending support to the ‘‘simulation or resonance theory of action’’ hypothesis formulated by Jeannerod [1]. According to this theory, observing, imagining, and even understanding motor actions activate the neural network involved in motor execution. Although these states differ from one another, there is a partial overlap between covert and overt actions. Mental practice is an accepted training method to improve performance in sports and rehabilitation [2]. Most experiments to date have focused on the upper limbs and investigated either observation or motor imagery, but not the simultaneous combination of both [3]. Recently, there has been a larger increase in the number of situations where people can engage in combinations of observation and motor imagery, i.e. a cognitive process in which a subject imagines himself/herself in the displayed movement situation. People do this mainly while playing ‘‘first-person shooter’’ computer games, while watching point-of-view (POV) scenes in some movies and while undergoing neurorehabilitation (for a review see [4,5]). With respect to neurorehabilitation, the presentation of limbs aim to (re)activate brain functions that have been abolished due to cortical or subcortical injury (e.g. [6,7]). The visual stimuli incorporated in the environment guide the motor simulation [8] and might support people who are not able to rehearse motor tasks extended periods of time [9]. To our knowledge, only four studies investigated such combi- nations of observation and motor imagery with functional MRI (fMRI). In the study by Cross et al. [8] dancers observed and mentally simulated another dancer’s movements; the experiment- ers found enhanced activation in brain regions classically associated with both action simulation and action observation. Macuga and Frey [10] showed that the observation of intransitive thumb-finger movements increased activation in a subset of the brain areas engaged during observation combined with imagina- tion. In the recent study by Nedelko et al. [2] brain activation of healthy subjects was investigated during action observation alone and during action observation with additional action imagery of video clips showing simple, object-related hand actions. They PLOS ONE | www.plosone.org 1 August 2013 | Volume 8 | Issue 8 | e72403