Early and late motor responses to action observation

Guido Barchiesi 0 1 Luigi Cattaneo 0 1 0 Received 13 June 2011; Accepted 18 April 2012 Advance Access publication 3 May 2012 This study was supported by the Provincia Autonoma di Trento and Fondazione Cassa di Risparmio di Trento e Rovereto. Trento , Via delle Regole, 101, I-38123 Mattarello (TN) , Italy 1 Center for Mind/Brain Sciences, University of Trento , Via delle Regole, 101, I-38123 Mattarello (TN) , Italy Is a short visuomotor associative training sufficient to reverse the visuomotor tuning of mirror neurons in adult humans? We tested the effects of associative training on corticospinal modulation during action observation in the 100-320 ms interval after action onset. In two separate experiments, the acceleration of transcranial magnetic stimulation (TMS)-induced movements was recorded before and after training participants to respond to observed acts with an opposite or similar behavior. Before training, TMS-induced accelerations mirrored the observed action at 250 and 320 ms. After training, responses at 250 ms were unchanged and still mirrored the stimuli, without any effect of training direction. Only at 320 ms, we observed training-dependent changes in evoked responses. A control experiment with non-biological rotational movements as visual stimuli indicated that spatial stimulus-response compatibility is not sufficient to account for the results of the two main experiments. We show that the effects of a short visuomotor associative training are not pervasive on the automatic mirror responses. Early (250 ms) responses were not influenced by training. Conversely only late (320 ms) responses changed according to the training direction. This biphasic time course indicates that two distinct mechanisms produce the automatic mirror responses and the newly learned visuomotor associations. - INTRODUCTION The motor system of primates responds to the sight of others movements with stimulus-specific motor programs that replicate congruently the observed behavior (Cattaneo and Rizzolatti, 2009). The neural substrate of such motor resonance resides probably in parieto-frontal mirror neurons. These are one among the many classes of parieto-frontal sensorimotor neurons that couple sensory information about the world around us with automatic goal-directed motor behavior (Rizzolatti et al., 1998). Their peculiar properties are those of firing during both the perception and the execution of motor acts. Transcranial magnetic stimulation (TMS) studies have been conducted in humans measuring the output of the primary motor cortex (M1) on the assumption that it is a measure of mirror neuron activity in the parieto-premotor mirror circuit, as suggested by studies combining single-pulse TMS over M1 with repetitive transcranial magnetic stimulation (rTMS) over the premotor cortex (Avenanti et al., 2007) or using dual-coil TMS (Koch et al., 2010; Catmur et al., 2011). It has been claimed that mirror neurons are a product of visuomotor-associative learning [associative sequence learning (ASL) hypothesis] occurring during visually guided behavior that necessarily couples the experiences of executing an action and seeing it similarly to a Pavlovian conditioned response (Heyes, 2010). The main experimental evidence in favor of the ASL theory is that by changing sensory motor contingencies, by training subjects to respond to seen actions with symmetrically opposite behavior, it is possible to transform in the short-term mirror neurons in counter-mirror neurons (Catmur et al., 2007, 2011). Counter-mirror neurons have reversed their tuning and code new associations of incongruent observed and executed behaviors. Such empirical data, however, imply that visuomotor parieto-frontal circuits are acutely re-tunable by arbitrary rules. Conversely, in our view, their visuomotor matching properties are more hard wired in the central nervous system of typically developed adult humans, and their stimulus/response curves can be shifted by recent experience but only to a limited extent (Cattaneo et al., 2010) without reversing it. The effects of counter-mirror training on the observers responses to action observation (Catmur et al., 2007, 2011) have been tested by stimulating M1 with single TMS pulses. In Catmur et al. (2007), corticospinal excitability was tested at intervals of 0, 320 and 640 ms from movement onset before and after the associative training. In Catmur et al. (2011), corticospinal excitability was tested before the training at the 200, 250 and 300 ms intervals from movement onset. However, after training, the authors tested only the 300 ms inter-stimulus interval (ISI) because of the interest in the effect of premotor stimulation over mirror motor facilitation, which was found at the 300 ms ISI only. The chronometry of the mirror effect to action observation is not entirely clear according to the available literature. Many studies used ongoing actions as visual stimuli, although the analyses were time locked to certain phases of the movement. In such studies, the timing of cortical activation is not clear because when watching continuous stimuli, the participants can in principle predict the forthcoming action. In these experiments, imitative responses were between 80 and 200 ms after informative visual cues (Borroni et al., 2005; Cattaneo et al., 2009). One neuromagnetic imaging study recorded activity time locked to objecthand interaction during an ongoing reach and grasp movement and found M1 to be active 40 ms from handobject interaction, but also in this case, the averaging trigger was not the onset of movement but its final phase (Nishitani and Hari, 2000). In that study, however, some indirect information on the timing of mirror responses can be inferred by comparing the latency of the occipital and motor peaks during imitation, which are separated by 200 ms. The aforementioned articles, regardless of the use of continuous or of event-related paradigms, are based on motor events that are predictable by the observer. It has been shown that, during ongoing movements, predictory elements are strongly represented in the observers motor system (Gangitano et al., 2004; Urgesi et al., 2010). Only a few studies used event-related techniques time locked to the onset of unpredictable movement. These showed motor modulation as early as 90100 ms after visual or auditory presentation of action stimuli (Lepage et al., 2010); however, this motor modulation was not muscle specific. Unpredictable movements were also used in an event-related paradigm by Catmur et al. (2011) who found in baseline conditions a muscle-specific mirror effect as early as 200 ms from movement onset. When processing categories of visual information other than upper limb movements, automatic motor responses are known to occur in an early time interval, between 100 and 200 ms from stimulus presentation. This has been shown for a variety of visual stimuli, such as the presentation of manipulable objects (Prabhu (...truncated)