Selective enhancement of motor cortical plasticity by observed mirror-matched actions Martin V. Sale a, ⁎, Jason B. Mattingley a, b a Queensland Brain Institute, The University of Queensland, Brisbane, QLD 4072, Australia b School of Psychology, The University of Queensland, Brisbane, QLD 4072, Australia abstract article info Article history: Accepted 8 February 2013 Available online 14 February 2013 Keywords: Action observation Mirror neurons Neuroplasticity Transcranial magnetic stimulation Paired associative stimulation Watching others learn a motor task can enhance an observer's own later performance when learning the same motor task. This is thought to be due to activation of the action observation (or mirror neuron) network. Here we show that the effectiveness of plasticity induced in human motor cortex (M1) is also significantly influenced by the nature of prior action observation. In separate sessions, 17 participants watched a video showing repeated goal-directed movements (action observation) involving either the right hand (congruent condition) or the same video mirror-reversed to simulate the left hand (incongruent condition). Participants then received pulses of transcranial magnetic stimulation over the hand area of left M1 paired with median nerve stimulation of the right hand (paired associative stimulation; PAS). The resting motor-evoked potential (MEP) in right abductor pollicis brevis (APB) increased significantly 20 minutes after PAS, but only when participants had previously watched the congruent video. In this condition, all participants showed an increase in MEP amplitude at 20 minutes post-PAS. There was no change in MEP amplitude following PAS when participants watched the in- congruent video. We conclude that prior action observation is a potent modulator of subsequent PAS-induced neuroplasticity, which may have important therapeutic applications. © 2013 Elsevier Inc. All rights reserved. Introduction Several experimental paradigms have recently been developed that induce plasticity within the human cortex using non-invasive stimulation (Huang et al., 2005; Pascual-Leone et al., 1994; Ridding et al., 2001; Stefan et al., 2000). Plasticity refers to a change in central nervous system structure and function, and is critical for learning and memory (Sanes and Donoghue, 2000), and recovery from nervous system injury (Nudo et al., 1996). Research has focussed on improv- ing functional recovery after brain injury (particularly stroke), with studies demonstrating improvement in function in stroke patients with such stimulation paradigms used on their own (Kim et al., 2006), or in conjunction with physical therapy (McDonnell et al., 2007). Unfortunately, the functional gains reported have generally been modest. This is probably due in part to individual differences in responsiveness to stimulation. Many factors appear important in mediating plasticity induction in humans (for review see Ridding and Ziemann (2010)). One such fac- tor is the history of prior cortical activity (Iyer et al., 2003; Muller et al., 2007; Stefan et al., 2006). One way of modifying cortical activity in the motor system is by observing others perform a matching move- ment. It is now well established that a specific set of neurons is activat- ed during both action observation and action execution. Originally found in monkeys (Rizzolatti et al., 1996a), but also thought to be present in humans (Chong et al., 2008; Kilner et al., 2009; Rizzolatti et al., 1996b), mirror neurons are active when individuals perform a goal-directed movement and also when they observe another individ- ual performing a matching goal-directed movement. Prior activation of such a network has been suggested to influence subsequent motor learning (Mattar and Gribble, 2005). An ‘artificial’ paradigm has been developed which mimics the use-dependent plasticity associated with motor learning (Stefan et al., 2000). This paired associative stimulation (PAS) paradigm pairs a periph- eral electrical stimulus delivered to a nerve innervating a muscle in the hand, with a pulse of transcranial magnetic stimulation (TMS) to the cor- responding motor representation in the contralateral motor cortex. The changes induced with PAS are thought to reflect long-term potentiation (LTP)-like changes in synaptic efficacy (Stefan et al., 2002). The circuits activated by PAS are the same as – or at least very similar to – the circuits activated by motor learning (Ziemann et al., 2004). Importantly, PAS re- quires no muscle activation to induce plasticity in motor cortex, and could potentially offer advantages in neurorehabilitation (compared with motor training), particularly when voluntary muscle activation is not possible (due to hemiplegia), or even deleterious (dystonia). We therefore investigated whether PAS-induced plasticity could be enhanced by prior action observation. Specifically, we hypothesised that action observation should enhance the effects of subsequent PAS-induced plasticity, but only when the observed action activates the same circuits as those modified during PAS. NeuroImage 74 (2013) 30–36 ⁎ Corresponding author. Fax: +61 7 3346 6301. E-mail address: m.sale@uq.edu.au (M.V. Sale). 1053-8119/$ – see front matter © 2013 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.neuroimage.2013.02.009 Contents lists available at SciVerse ScienceDirect NeuroImage journal homepage: www.elsevier.com/locate/ynimg