Bernadette M. Fitzgibbon

A transcranial magnetic stimulation study of the effect of visual orientation on the putative human mirror neuron system

Mirror neurons are a class of motor neuron that are active during both the performance and observation of behavior, and have been implicated in interpersonal understanding. There is evidence to suggest that the mirror response is modulated by the perspective from which an action is presented (e.g., egocentric or allocentric). Most human research, however, has only examined this when presenting intransitive actions. Twenty-three healthy adult participants completed a transcranial magnetic stimulation experiment that assessed corticospinal excitability whilst viewing transitive hand gestures from both egocentric (i.e., self) and allocentric (i.e., other) viewpoints. Although action observation was associated with increases in corticospinal excitability (reflecting putative human mirror neuron activity), there was no effect of visual perspective. These findings are discussed in the context of contemporary theories of mirror neuron ontogeny, including models concerning associative learning and evolutionary adaptation.

Removing artefacts from TMS-EEG recordings using independent component analysis: Importance for assessing prefrontal and motor cortex network properties

INTRODUCTION The combination of transcranial magnetic stimulation and electroencephalography (TMS-EEG) is emerging as a powerful tool for causally investigating cortical mechanisms and networks. However, various artefacts contaminate TMS-EEG recordings, particularly over regions such as the dorsolateral prefrontal cortex (DLPFC). The aim of this study was to substantiate removal of artefacts from TMS-EEG recordings following stimulation of the DLPFC and motor cortex using independent component analysis (ICA). METHODS 36 healthy volunteers (30.8 ± 9 years, 9 female) received 75 single TMS pulses to the left DLPFC or left motor cortex while EEG was recorded from 57 electrodes. A subset of 9 volunteers also received 50 sham pulses. The large TMS artefact and early muscle activity (-2 to ~15 ms) were removed using interpolation and the remaining EEG signal was processed in two separate ICA runs using the FastICA algorithm. Five sub-types of TMS-related artefacts were manually identified: remaining muscle artefacts, decay artefacts, blink artefacts, auditory-evoked potentials and other noise-related artefacts. The cause of proposed blink and auditory-evoked potentials was assessed by concatenating known artefacts (i.e. voluntary blinks or auditory-evoked potentials resulting from sham TMS) to the TMS trials before ICA and evaluating grouping of resultant independent components (ICs). Finally, we assessed the effect of removing specific artefact types on TMS-evoked potentials (TEPs) and TMS-evoked oscillations. RESULTS Over DLPFC, ICs from proposed muscle and decay artefacts correlated with TMS-evoked muscle activity size, whereas proposed TMS-evoked blink ICs combined with voluntary blinks and auditory ICs with auditory-evoked potentials from sham TMS. Individual artefact sub-types characteristically distorted each measure of DLPFC function across the scalp. When free of artefact, TEPs and TMS-evoked oscillations could be measured following DLPFC stimulation. Importantly, characteristic TEPs following motor cortex stimulation (N15, P30, N45, P60, N100) could be recovered from artefactual data, corroborating the reliability of ICA-based artefact correction. CONCLUSIONS Various different artefacts contaminate TMS-EEG recordings over the DLPFC and motor cortex. However, these artefacts can be removed with apparent minimal impact on neural activity using ICA, allowing the study of TMS-evoked cortical network properties.

A double-blind, randomized trial of deep repetitive transcranial magnetic stimulation (rTMS) for autism spectrum disorder.

BACKGROUND Biomedical treatment options for autism spectrum disorder (ASD) are extremely limited. Repetitive transcranial magnetic stimulation (rTMS) is a safe and efficacious technique when targeting specific areas of cortical dysfunction in major depressive disorder, and a similar approach could yield therapeutic benefits in ASD, if applied to relevant cortical regions. OBJECTIVE The aim of this study was to examine whether deep rTMS to bilateral dorsomedial prefrontal cortex improves social relating in ASD. METHODS 28 adults diagnosed with either autistic disorder (high-functioning) or Aspergers disorder completed a prospective, double-blind, randomized, placebo-controlled design with 2 weeks of daily weekday treatment. This involved deep rTMS to bilateral dorsomedial prefrontal cortex (5 Hz, 10-s train duration, 20-s inter-train interval) for 15 min (1500 pulses per session) using a HAUT-Coil. The sham rTMS coil was encased in the same helmet of the active deep rTMS coil, but no effective field was delivered into the brain. Assessments were conducted before, after, and one month following treatment. RESULTS Participants in the active condition showed a near significant reduction in self-reported social relating symptoms from pre-treatment to one month follow-up, and a significant reduction in social relating symptoms (relative to sham participants) for both post-treatment assessments. Those in the active condition also showed a reduction in self-oriented anxiety during difficult and emotional social situations from pre-treatment to one month follow-up. There were no changes for those in the sham condition. CONCLUSION Deep rTMS to bilateral dorsomedial prefrontal cortex yielded a reduction in social relating impairment and socially-related anxiety. Further research in this area should employ extended rTMS protocols that approximate those used in depression in an attempt to replicate and amplify the clinical response.

The neural underpinnings of vicarious experience.

In recent decades there has been an explosion of empirical research into the social cognitive processes that underlie our social interactions. Coinciding with, or perhaps driving, the interest within this area is the development of modern neuroscientific techniques bringing real world experiences into the laboratory to produce biological models of how we experience and interact with other people. In this research topic, we present a range of expert manuscripts that focus on one primary aspect of social cognition: the ability to recognize, understand and, in some cases, “feel” the experience of another person. To date, neuroscience research in this area has identified shared neural networks whereby we process anothers action, emotion or sensation through overlapping brain regions as if we were carrying out that same action or experiencing that same emotion or sensation. Intriguingly, this research has shown that such vicarious activation of brain networks can span from an automatic and unconscious process through to an overt experience of the emotion or sensation of that observed in another person. By investigating vicarious processes as well as exploring the influence of interpersonal characteristics such as empathy, we are taking a step toward better understanding the relationship between the social brain and social behavior. This includes the decision to make a pro-social response vs. fleeing potentially dangerous, or even socially awkward situations, such as witnessing another person embarrass themselves. Moreover, this research area has substantial implications for understanding disease and improving treatment options for people who experience psychiatric or neurological illness including autism spectrum disorder, where impairment in aspects of social functioning is a key feature. However, even beyond disorders where social function may be diagnostic, social impairments and difficulties in social relationships can have substantial functional consequences, as is often reported in illnesses such as depression and schizophrenia. Ultimately, understanding the neurobiology of social processes will provide the platform for targeted and appropriate treatment interventions. In the work that follows, this research topic brings together a number of opinions, perspectives, hypotheses and theories, general commentaries, reviews and original research articles. Several key themes can be identified ranging from: Definitional considerations including the distinction between vicarious and empathic experiences (Paulus et al., 2013), and why overt vicarious experiences may not represent a new form of synaesthesia, where sensory input in one domain results in a sensory experience in another (Rothen and Meier, 2013); Exploration of vicarious shared neural experiences in the general population from physical touch and injury (Bufalari and Ionta, 2013) through to ostracism (Wesselmann et al., 2013) and how vicarious experience may differ between people according to attention (Morelli and Lieberman, 2013), interpersonal and personality differences (Schaefer et al., 2013; Vandenbroucke et al., 2013) such as empathy, and the influence of psychopathic (Marcoux et al., 2013) or autistic (Cooper et al., 2013) traits. Additional modulating factors of vicarious experience are also considered including expertise seen in physicians (Newton, 2013), the influence of the mother-child bond (Manini et al., 2013), the experimental administration of oxytocin and the effect of visual orientation (i.e., self vs. other) (Burgess et al., 2013). The investigation of atypical vicarious experiences in the general population such as shared touch (Banissy and Ward, 2013) and pain and how feeling the pain of others may be linked with self-other confusion and prior pain experience (Derbyshire et al., 2013). Through to a physiological study exploring the experience of misophonia, describing a sensitivity to sound that can substantially limit ones ability to interact with others (Edelstein et al., 2013), and a commentary of why vicarious perception may drive contagious scratching (Ward et al., 2013); The discussion of vicarious experiences in atypical populations including evidence against an impairment in shared neural networks in ASD (Enticott et al., 2013) and an argument for how models of vicarious pain experience may help us understand the relationship between core ASD symptoms better (Fitzgibbon et al., 2013); Finally, the role of vicarious experience including vicarious motor system activation in understanding the behaviors of others (Avenanti et al., 2013) and how group membership may influence such processing and influence how we interact with others (Eres and Molenberghs, 2013). Taken together, this research topic presents cutting edge research in a growing field which, while by no means definitive, represents exciting developments in the neurobiology underlying sharing experiences with others.

High incidence of ‘synaesthesia for pain’ in amputees

Synaesthesia for pain is a phenomenon where a person experiences pain when observing or imagining another in pain. Anecdotal reports of this type of experience have most commonly occurred in individuals who have lost a limb. Distinct from phantom pain, synaesthesia for pain is triggered specifically in response to pain in another. Here, we provide the first preliminary investigation into synaesthesia for pain in amputees to determine the incidence and characteristics of this intriguing phenomenon. Self-referring amputees (n=74) answered questions on synaesthesia for pain within a broader survey of phantom pain. Of the participants, 16.2% reported that observing or imagining pain in another person triggers their phantom pain. Further understanding of synaesthesia for pain may provide a greater insight to abnormal empathic function in clinical populations as well as therapeutic intervention for at risk groups.

Emotional valence modulates putative mirror neuron activity

Mirror neurons are thought to facilitate emotion processing, but it is unclear whether the valence of an emotional presentation (positive or negative) can influence subsequent mirror neuron activity. Participants completed a transcranial magnetic stimulation experiment that involved stimulation of the primary motor cortex, and electromyography recording from contralateral hand muscles. This was performed while participants viewed videos of either a static hand or a transitive hand action preceded by either a positive or negative stimulus. Corticospinal excitability facilitation during action observation was significantly greater following the presentation of negative (relative to positive) stimuli; this was evident for the first dorsal interosseous muscle (which was central to the observed grasp), but not for the abductor digiti minimi muscle. This study provides evidence that emotional valence can modulate mirror neuron activity, which may reflect an adaptive mechanism.

Transcranial direct current stimulation (tDCS) of the inferior frontal gyrus disrupts interpersonal motor resonance

Interpersonal motor resonance (IMR) is presumed to result from activity within the human mirror neuron system, which itself is thought to comprise the inferior parietal lobule (IPL) and inferior frontal gyrus (IFG). Twenty healthy adults underwent anodal, cathodal, and sham transcranial direct current stimulation (tDCS) to either IPL or IFG immediately before the assessment of IMR (using transcranial magnetic stimulation). IMR (i.e., motor-evoked potential amplitude during transitive action observation relative to static observation) was significantly reduced following both anodal and cathodal stimulation of IFG (relative to sham), but there was no effect of stimulation for IPL. These data support the role of IFG, a presumed mirror neuron region, in IMR.

Ouch! My phantom leg jumps/hurts when you stab "my" virtual hand.

Pain synaesthetes experience pain in a presensitised region when observing or imagining another person in pain. We conducted an upper-limb embodiment study using a modified rubber-hand illusion in which lower-limb amputees originally participated as control subjects for the upper-limb amputees. While we found all subjects experienced topographic illusory sensations, we also serendipitously found that lower-limb amputee pain synaesthetes experienced pain or a motor response in their phantom leg when the embodied hand was threatened (eg with a retractable knife, mousetrap, or syringe) or submitted to high-frequency stimulation (eg vibration). Embodiment illusions were brought about by touching, manipulating, or threatening a rubber or real hand which was observed through a mirror so that it was superimposed upon the target hand (phantom hand for upper-limb amputees, or real hand in others). Participants included eight pain synaesthetes (six lower-limb amputees, one upper-limb amputee, and one nonamputee), and thirty-one controls (eight lower-limb amputees, twelve upper-limb amputees, and eleven non-amputees). We documented participants subjective reports, together with quantitative measures including the Questionnaire Measure of Emotional Empathy. We found no association between pain synaesthesia and empathy scores. On the basis of related literature we suggest that pain synaesthetes likely experienced phantom-leg pain because (a) the motor system was already engaged during visual capture; (b) threatening stimuli, to which they are hyper-vigilant, triggered avoidance or ‘escape’ motor schemata; and (c) there could be no feedback confirming that initiated motor schemata for the phantom limb were successfully performed. Ultimately, we have further defined this new condition, synaesthesia for pain, as not only having a sensory pain component, but also a key motor component, manifesting itself in avoidance, contraction, and withdrawal ‘actions’.

Affective, sensory and empathic sharing of another's pain: The Empathy for Pain Scale.

Through two studies, we introduce and validate the Empathy for Pain Scale (EPS), which characterizes the phenomenology of empathy for pain, including the vicarious experience of pain when seeing others in pain.

Modulation of putative mirror neuron activity by both positively and negatively valenced affective stimuli: a TMS study.

Research indicates that mirror neurons are important for social cognition, including emotion processing. Emerging evidence, however, also reveals that emotional stimuli might be capable of modulating human mirror neuron system (MNS) activity. The current study used transcranial magnetic stimulation (TMS) to assess putative mirror neuron function following emotionally evocative images in twenty healthy adults. Participants observed videos of either a transitive hand action or a static hand while undergoing TMS of the primary motor cortex. In order to examine the effect of emotion on the MNS, each video was preceded by an image of either a positive, negative or neutral valence. MNS activity was found to be augmented by both the positive and negative (relative to neutral) stimuli, thus providing empirical support for a bi-directional link between emotion and the MNS, whereby both positively and negatively valenced stimuli are capable of facilitating mirror neuron activity. The potential adaptive significance of this finding is discussed.