Lisa Aziz-Zadeh PhD

While exteroceptive sensory processing is a hallmark of autism spectrum disorder, how interoceptive processing may impact and contribute to symptomatology remains unclear. In this comprehensive narrative review on interoception in autism, we discuss: 1) difficulties with assessing interoception; 2) potential interoceptive differences; 3) interactions between neural systems for interoception, attention, sensorimotor processing, and cognition; and 4) potential differences in neural circuits involved in interoception. In general, there are mixed findings on potential interoception differences in autism. Nevertheless, some data indicate differences in integration of interoceptive and exteroceptive information may contribute to autism symptomatology. Neurologically, interoceptive processing in autism may be impacted by potential differences in the development, morphometry, and connectivity of key interoceptive hubs (vagal processing, brainstem, thalamus, insula), though much work is needed on this topic.

Youth diagnosed with autism spectrum disorder (ASD) and those with developmental coordination disorder (DCD) are at heightened risk for co-occurring mental health diagnoses, especially anxiety and attention-deficit/hyperactivity disorder (ADHD). However, caregiver-child agreement on presence of related symptoms in populations with neurodevelopmental conditions is not well understood. Here, we examine the extent to which 37 ASD, 26 DCD, and 40 typically developing children and their caregivers agree on the degree of the child's symptoms of anxiety and ADHD. All caregiver-child dyads completed the Screen for Child Anxiety Related Emotional Disorders and Conners 3 ADHD Index. Across groups, intraclass correlations indicated generally poor agreement on anxiety and ADHD symptomatology. Although youth generally reported greater internalizing symptoms (i.e., anxiety), caregivers tended to report more observable externalizing behaviors (i.e., ADHD). Together, the results of this study support the need for a multi-informant approach in assessments of anxiety and ADHD in youth with neurodevelopmental disorders.

Autism spectrum disorder (ASD) and Developmental Coordination Disorder (DCD) are distinct clinical groups with overlapping motor features. We attempted to (1) differentiate children with ASD from those with DCD, and from those typically developing (TD) (ages 8–17; 18 ASD, 16 DCD, 20 TD) using a 5-min coloring game on a smart tablet and (2) identify neural correlates of these differences. We utilized standardized behavioral motor assessments (e.g. fine motor, gross motor, and balance skills) and video recordings of a smart tablet task to capture any visible motor, behavioral, posture, or engagement differences. We employed machine learning analytics of motor kinematics during a 5-min coloring game on a smart tablet. Imaging data was captured using functional magnetic resonance imaging (fMRI) during action production tasks. While subject-rated motor assessments could not differentiate the two clinical groups, machine learning computational analysis provided good predictive discrimination: between TD and ASD (76% accuracy), TD and DCD (78% accuracy), and ASD and DCD (71% accuracy). Two kinematic markers which strongly drove categorization were significantly correlated with cerebellar activity. Findings demonstrate unique neuromotor patterns between ASD and DCD relate to cerebellar function and present a promising route for computational techniques in early identification. These are promising preliminary results that warrant replication with larger samples.

Keywords. Autism spectrum disorders, Developmental coordination disorder, Machine learning, fMRI, Early detection, Smart tablet

Purpose of Review. While there are reports of differences in emotion processing in autism, it is less understood whether the emotion of disgust, in particular, plays a significant role in these effects. Here, we review literature on potential disgust processing differences in autism and its possible associations with autistic traits.

Recent Findings. In autism, there is evidence for differences in physical disgust processing, pica behaviors, attention away from other’s disgust facial expressions, and differences in neural activity related to disgust processing. In typically developing individuals, disgust processing is related to moral processing, but modulated by individual differences in interoception and alexithymia.

Summary. Autistic individuals may experience atypical disgust, which may lead to difficulty avoiding contaminants and affect socio-emotional processing. In autism, such outcomes may lead to increased occurrences of illness, contribute to gastrointestinal issues, diminish vicarious learning of disgust expression and behaviors, and potentially contribute to differences in processes related to moral reasoning, though further research is needed.

Prior studies show differences in empathy and affect-recognition ability between those with autism spectrum disorder (ASD) and typically developing (TD) individuals. Autistic individuals also exhibit increased behavioral, gastrointestinal, and sleep issues. In the current study, we explored the differences in empathy and affect recognition between the ASD and TD groups; and we investigated their associations with conditions co-occurring in ASD. A total of 54 TD and 56 ASD children (8–17 years) were included. As compared to the TD group, the ASD group showed lower scores for affect recognition and perspective taking (PT) and higher scores for personal distress (PD). Interestingly, results from hierarchical linear regressions suggested that disparities in the PD and PT between the groups were primarily attributable to attenuated levels of alexithymia, rather than being mediated by the presence of an autism diagnosis. Differences in affect-recognition ability, however, were mediated by both an autism diagnosis and alexithymia. We also found significant correlations between empathy and affect recognition and measures of related conditions common in ASD. Alexithymia, hence, contributes to difficulties in empathy while both alexithymia and autism are associated with affect-recognition ability in ASD. Additionally, the association between affect recognition and empathic ability with co-occurring conditions in ASD needs to be considered during assessments and interventions.

Keywords. autism; alexithymia; empathy; affect recognition; anxiety; sleep; gastrointestinal issues

About 85% of children with autism spectrum disorder (ASD) experience comorbid motor impairments, making it unclear whether white matter abnormalities previously found in ASD are related to social communication deficits, the hallmark of ASD, or instead related to comorbid motor impairment. Here we aim to understand specific white matter signatures of ASD beyond those related to comorbid motor impairment by comparing youth (aged 8–18) with ASD (n = 22), developmental coordination disorder (DCD; n = 16), and typically developing youth (TD; n = 22). Diffusion weighted imaging was collected and quantitative anisotropy, radial diffusivity, mean diffusivity, and axial diffusivity were compared between the three groups and correlated with social and motor measures. Compared to DCD and TD groups, diffusivity differences were found in the ASD group in the mid-cingulum longitudinal and u-fibers, the corpus callosum forceps minor/anterior commissure, and the left middle cerebellar peduncle. Compared to the TD group, the ASD group had diffusivity differences in the right inferior frontal occipital/extreme capsule and genu of the corpus callosum. These diffusion differences correlated with emotional deficits and/or autism severity. By contrast, children with DCD showed unique abnormality in the left cortico-spinal and cortico-pontine tracts.

Trial Registration. All data are available on the National Institute of Mental Health Data Archive: https://nda.nih.gov/edit_collection.html?id=2254.

Previous research has shown that individuals with autism spectrum disorder (ASD) and developmental coordination disorder (DCD) may have overlapping social and motor skill impairments. This study compares ASD, DCD, and typically developing (TD) youth on a range of social, praxis and motor skills, and investigates the relationship between these skills in each group. Data were collected on participants aged 8–17 (n = 33 ASD, n = 28 DCD, n = 35 TD). Overall, the clinical groups showed some similar patterns of social and motor impairments but diverged in praxis impairments, cognitive empathy, and Theory of Mind ability. When controlling for both social and motor performance impairments, the ASD group showed significantly lower accuracy on imitation of meaningful gestures and gesture to command, indicating a prominent deficit in these praxis skills in ASD.

Developmental Coordination Disorder (DCD) is one of the least studied and understood developmental disorders. One area that has been minimally investigated in DCD is potential issues with sensory modulation. Further, in other neurodevelopmental disorders (e.g., autism spectrum disorder (ASD)) sensory modulation is related to many other challenges (e.g., social issues, repetitive behaviors, anxiety); however, such potential relationships in children with DCD have been largely unexplored. The purpose of this study is to explore sensory modulation differences in DCD and to understand the relationships between sensory modulation and social emotional measures, behavior, and motor skills in DCD in comparison to ASD and typically developing (TD) peers. Participants (aged 8–17) and their caregivers (DCD, N = 26; ASD, N = 57; and TD, N = 53) completed behavioral and clinical measures. The results indicated that 31% of the DCD group showed sensory modulation difficulties, with the DCD group falling between the ASD and TD groups. In the DCD group, sensory modulation was significantly associated with anxiety, empathic concern, repetitive behaviors, and motor skills. Data are compared to patterns seen in ASD and TD groups and implications for interventions are discussed.

Keywords. developmental coordination disorder; sensory processing; autism spectrum disorder; behavior; social emotional; motor skills; dyspraxia; empathy; sensory modulation; anxiety

Some studies suggest that individuals with autism spectrum disorder have reduced emotional empathy while others do not. The presence of co-occurring alexithymia in autism spectrum disorder and differences in interoception have been associated with reductions in empathic ability. To fully explore the relationships between interoception, alexithymia, and emotional empathy, we collected self-report and interview data in 35 youth with autism spectrum disorder and 40 typically developing controls (ages 8–17 years). The autism spectrum disorder sample had increased alexithymia and physiological hyperarousal compared to typically developing controls, but there were no group differences in interoception or emotional empathy. Alexithymia severity correlated with higher personal distress in both groups and with lower empathic concern in the autism spectrum disorder group. Within the autism spectrum disorder group, higher incidence of reports of bodily sensation when describing emotional experience correlated with lower personal distress and lower alexithymia. In addition, although empathic concern was negatively correlated with alexithymia in the autism spectrum disorder group, across groups, the alexithymia hypothesis was supported in only the personal distress domain of emotional empathy. These results suggest emotional empathy; personal distress, in particular, is not intrinsically impaired in autism spectrum disorder.

Previous studies indicate that damage to motor brain regions impacts comprehension of literal action-related language. However, whether such damage also impacts comprehension of action-metaphors remains unknown. Such a finding would support the notion that metaphors are grounded in sensorimotor representations. Here we tested this hypothesis by comparing comprehension of novel, conventional, and frozen action and non-action metaphors in 14 right-handed adults with right-sided mild to moderate paresis following left hemisphere motor stroke and 23 neurotypical participants. Consistent with our hypothesis, results indicated that only in the stroke group, accuracy for action metaphors was significantly lower than for non-action metaphors. Further, in the stroke group, accuracy was significantly worse in the following pattern: novel < conventional < frozen action metaphors. These results strongly support the notion that motor-related brain regions are important not only for literal action-related language comprehension, but also for action-related metaphor comprehension, especially for less familiar metaphors.

Keywords. Embodied semantics theory; Motor stroke; Motor metaphor; Abstract language; Graded Salience Hypothesis

Gastrointestinal dysfunction is one of the most prevalent physiological symptoms of autism spectrum disorder (ASD). A growing body of largely preclinical research suggests that dysbiotic gut microbiota may modulate brain function and social behavior, yet little is known about the mechanisms that underlie these relationships and how they may influence the pathogenesis or severity of ASD. While various genetic and environmental risk factors have been implicated in ASD, this review aims to provide an overview of studies elucidating the mechanisms by which gut microbiota, associated metabolites, and the brain interact to influence behavior and ASD development, in at least a subgroup of individuals with gastrointestinal problems. Specifically, we review the brain-gut-microbiome system and discuss findings from current animal and human studies as they relate to social-behavioral and neurological impairments in ASD, microbiota-targeted therapies (i.e., probiotics, fecal microbiota transplantation) in ASD, and how microbiota may influence the brain at molecular, structural, and functional levels, with a particular interest in social and emotion-related brain networks. A deeper understanding of microbiome-brain-behavior interactions has the potential to inform new therapies aimed at modulating this system and alleviating both behavioral and physiological symptomatology in individuals with ASD.

Keywords. autism spectrum disorder; brain-gut-microbiome system; gut-brain axis; microbiome; probiotics; tryptophan pathway

A deficit in pre‐cognitively mirroring other people's actions and experiences may be related to the social impairments observed in autism spectrum disorder (ASD). However, it is unclear whether such embodied simulation deficits are unique to ASD or instead are related to motor impairment, which is commonly comorbid with ASD. Here we aim to disentangle how, neurologically, motor impairments contribute to simulation deficits and identify unique neural signatures of ASD. We compare children with ASD (N = 30) to children with Developmental Coordination Disorder (DCD; N = 23) as well as a typically developing group (N = 33) during fMRI tasks in which children observe, imitate, and mentalize about other people's actions. Results indicate a unique neural signature in ASD: during action observation, only the ASD group shows hypoactivity in a region important for simulation (inferior frontal gyrus, pars opercularis, IFGop). However, during a motor production task (imitation), the IFGop is hypoactive for both ASD and DCD groups. For all tasks, we find correlations across groups with motor ability, even after controlling for age, IQ, and social impairment. Conversely, across groups, mentalizing ability is correlated with activity in the dorsomedial prefrontal cortex when controlling for motor ability. These findings help identify the unique neurobiological basis of ASD for aspects of social processing. Furthermore, as no previous fMRI studies correlated brain activity with motor impairment in ASD, these findings help explain prior conflicting reports in these simulation networks.

Difficulty processing sensory information may impede progress in school for students with autism spectrum disorder (ASD). We explore the relationship between sensory processing and school performance in 26 high‐functioning youths with ASD and 26 controls (age 8–14) using measures of sensory, social, cognitive, and academic functioning. In the ASD group, bivariate Pearson correlations indicated a significant positive relationship between intelligence quotient (IQ) and the School Competence Scale (SCS) of the Child Behavior Checklist (CBCL), and a significant negative relationship between Dunn's Sensory Processing Framework and SCS scores. Final hierarchical multiple linear regression model accounting for SCS scores in ASD included IQ, ADHD symptoms, and sensory features. An interaction between increased sensory sensitivity with reduced sensory avoidance behaviors explained the greatest amount of variance in SCS, meaning school performance is lowest for children with greater hypersensitivity and fewer avoidance behaviors. Results indicate a strong impact of sensory processing on school performance in ASD.

Recent research has reported motor impairment similarities between children with developmental coordination disorder (DCD) and a subgroup of individuals with autism spectrum disorder (ASD). However, there is a debate as to whether DCD is a co-occurring diagnosis in individuals with ASD and motor impairments (ASDd), or if motor impairments in ASD are distinct from DCD. However, the etiology of motor impairments is not well understood in either disorder. Clarifying comorbidities in ASD is important to determine different etiopathological phenotyping clusters in ASD and to understand the variety of genetic and environmental factors that contribute to the disorder. Furthermore, this distinction has important therapeutic relevance. Here we explore the current neuroimaging findings in ASD and DCD and discusses possible neural mechanisms that underlie similarities and differences between the disorders.

Keywords: Autism spectrum disorder (ASD); developmental coordination disorder (DCD); action observation network (AON); functional magnetic resonance imaging (fMRI); resting state; diffusion weighted imaging (DWI)

Abnormal sensory-based behaviors are a defining feature of autism spectrum disorders (ASD). Dr. A. Jean Ayres was the first occupational therapist to conceptualize Sensory Integration (SI) theories and therapies to address these deficits. Her work was based on neurological knowledge of the 1970s. Since then, advancements in neuroimaging techniques make it possible to better understand the brain areas that may underlie sensory processing deficits in ASD. In this article, we explore the postulates proposed by Ayres (i.e., registration, modulation, motivation) through current neuroimaging literature. To this end, we review the neural underpinnings of sensory processing and integration in ASD by examining the literature on neurophysiological responses to sensory stimuli in individuals with ASD as well as structural and network organization using a variety of neuroimaging techniques. Many aspects of Ayres’ hypotheses about the nature of the disorder were found to be highly consistent with current literature on sensory processing in children with ASD but there are some discrepancies across various methodological techniques and ASD development. With additional characterization, neurophysiological profiles of sensory processing in ASD may serve as valuable biomarkers for diagnosis and monitoring of therapeutic interventions, such as SI therapy.

Keywords: Autism Spectrum Disorder (ASD); Ayres Sensory Integration (ASI); sensory processing; functional magnetic resonance imaging (fMRI)

The time is ripe to integrate burgeoning evidence of the important role of sensory and motor functioning in mental health within the National Institute of Mental Health’s [NIMH] Research Domain Criteria [RDoC] framework (National Institute of Mental Health, n.d.a), a multi-dimensional method of characterizing mental functioning in health and disease across all neurobiological levels of analysis ranging from genetic to behavioral. As the importance of motor processing in psychopathology has been recognized (Bernard & Mittal, 2015; Garvey & Cuthbert, 2017; National Institute of Mental Health, 2019), here we focus on sensory processing. First, we review the current design of the RDoC matrix, noting sensory features missing despite their prevalence in multiple mental illnesses. We identify two missing classes of sensory symptoms that we widely define as (1) sensory processing, including sensory sensitivity and active sensing, and (2) domains of perceptual signaling, including interoception and proprioception, which are currently absent or underdeveloped in the perception construct of the cognitive systems domain. Then, we describe the neurobiological basis of these psychological constructs and examine why these sensory features are important for understanding psychopathology. Where appropriate, we examine links between sensory processing and the domains currently included in the RDoC matrix. Throughout, we emphasize how the addition of these sensory features to the RDoC matrix is important for understanding a range of mental health disorders. We conclude with the suggestion that a separate sensation and perception domain can enhance the current RDoC framework, while discussing what we see as important principles and promising directions for the future development and use of the RDoC.

Background. Increased activity in the lesioned hemisphere has been related to improved poststroke motor recovery. However, the role of the dominant hemisphere—and its relationship to activity in the lesioned hemisphere—has not been widely explored.

Objective. Here, we examined whether the dominant hemisphere drives the lateralization of brain activity after stroke and whether this changes based on if the lesioned hemisphere is the dominant hemisphere or not.

Methods. We used fMRI to compare cortical motor activity in the action observation network (AON), motor-related regions that are active both during the observation and execution of an action, in 36 left hemisphere dominant individuals. Twelve individuals had nondominant, right hemisphere stroke, twelve had dominant, left-hemisphere stroke, and twelve were healthy age-matched controls. We previously found that individuals with left dominant stroke show greater ipsilesional activity during action observation. Here, we examined if individuals with nondominant, right hemisphere stroke also showed greater lateralized activity in the ipsilesional, right hemisphere or in the dominant, left hemisphere and compared these results with those of individuals with dominant, left hemisphere stroke.

Results. We found that individuals with right hemisphere stroke showed greater activity in the dominant, left hemisphere, rather than the ipsilesional, right hemisphere. This left-lateralized pattern matched that of individuals with left, dominant hemisphere stroke, and both stroke groups differed from the age-matched control group.

Conclusions. These findings suggest that action observation is lateralized to the dominant, rather than ipsilesional, hemisphere, which may reflect an interaction between the lesioned hemisphere and the dominant hemisphere in driving lateralization of brain activity after stroke. Hemispheric dominance and laterality should be carefully considered when characterizing poststroke neural activity.

Over the past decade many studies indicate that we utilize our own motor system to understand the actions of other people. This mirror neuron system (MNS) has been proposed to be involved in social cognition and motor learning. However, conflicting findings regarding the underlying mechanisms that drive these shared circuits make it difficult to decipher a common model of their function. Here we propose adapting a “value-driven” model to explain discrepancies in the human mirror system literature and to incorporate this model with existing models. We will use this model to explain discrepant activation patterns in multiple shared circuits in the human data, such that a unified model may explain reported activation patterns from previous studies as a function of value.

Stroke is the leading cause of adult disability worldwide, with up to two-thirds of individuals experiencing long-term disabilities. Large-scale neuroimaging studies have shown promise in identifying robust biomarkers (e.g., measures of brain structure) of long-term stroke recovery following rehabilitation. However, analyzing large rehabilitation-related datasets is problematic due to barriers in accurate stroke lesion segmentation. Manually-traced lesions are currently the gold standard for lesion segmentation on T1-weighted MRIs, but are labor intensive and require anatomical expertise. While algorithms have been developed to automate this process, the results often lack accuracy. Newer algorithms that employ machine-learning techniques are promising, yet these require large training datasets to optimize performance. Here we present ATLAS (Anatomical Tracings of Lesions After Stroke), an open-source dataset of 304 T1-weighted MRIs with manually segmented lesions and metadata. This large, diverse dataset can be used to train and test lesion segmentation algorithms and provides a standardized dataset for comparing the performance of different segmentation methods. We hope ATLAS release 1.1 will be a useful resource to assess and improve the accuracy of current lesion segmentation methods.

It has been argued that metaphor and emotion processing are tightly linked together. Here we explore whether neuroscientific evidence supports this claim.

The aim of this study was to reveal cortical areas that may contribute to the movement difficulties seen in children with Developmental Coordination Disorder (DCD). Specifically, we hypothesized that there may be a deficit in the mirror neuron system (MNS), a neural system that responds to both performed and observed actions. Using functional MRI, 14 boys with DCD (x̄ = 10.08 years ± 1.31, range = 7.83 - 11.58 years) and 12 typically developing controls (x̄ = 10.10 years ± 1.15, range = 8.33 - 12.00 years) were scanned observing, executing and imitating a finger sequencing task using their right hand. Cortical activations of mirror neuron regions, including posterior inferior frontal gyrus (IFG), ventral premotor cortex, anterior inferior parietal lobule and superior temporal sulcus were examined. Children with DCD had decreased cortical activation mirror neuron related regions, including the precentral gyrus and IFG, as well as in the posterior cingulate and precuneus complex when observing the sequencing task. Region of interest analysis revealed lower activation in the pars opercularis, a primary MNS region, during imitation in the DCD group compared to controls. These findings provide some preliminary evidence to support a possible MNS dysfunction in children with DCD.

Functional magnetic resonance imaging has significant potential in the study and treatment of neurological disorders and stroke. Region of interest (ROI) analysis in such studies allows for testing of strong a priori clinical hypotheses with improved statistical power. A commonly used automated approach to ROI analysis is to spatially normalize each participant's structural brain image to a template brain image and define ROIs using an atlas. However, in studies of individuals with structural brain lesions such as stroke, the gold standard approach may be to manually hand-draw ROIs on each participant's non-normalized structural brain image. Automated approaches to ROI analysis are faster and more standardized, yet are susceptible to preprocessing error (e.g., normalization error) that can be greater in lesioned brains. The manual approach to ROI analysis has high demand for time and expertise but may provide a more accurate estimate of brain response. In this study, we directly compare commonly used automated and manual approaches to ROI analysis by reanalyzing data from a previously published hypothesis-driven cognitive fMRI study involving individuals with stroke. The ROI evaluated is the pars opercularis of the inferior frontal gyrus. We found a significant difference in task-related effect size and percent activated voxels in this ROI between the automated and manual approaches to ROI analysis. Task interactions, however, were consistent across ROI analysis approaches. These findings support the use of automated approaches to ROI analysis in studies of lesioned brains, provided they employ a task interaction design.

Individuals with psychopathy possess emotional and behavioral abnormalities. Two neural regions, involved in behavioral control and emotion regulation, are often implicated: amygdala and ventromedial prefrontal cortex (VMPFC). Recently, in studies using adult criminal populations, reductions in microstructural integrity of the white matter connections (i.e., uncinate fasciculus (UF)) between these two neural regions have been discovered in criminals with psychopathy, supporting the notion of neural dysfunction in the amygdala-VMPFC circuit. Here, a young adult, community sample is used to assess whether psychopathic traits modulate microstructural integrity of UF, and whether this relationship is dependent upon levels of trait anxiety, which is sometimes used to distinguish subtypes of psychopathy. Results reveal a negative association between psychopathic traits and microstructural integrity of UF, supporting previous findings. However, no moderation of the relationship by trait anxiety was discovered. Findings provide further support for the notion of altered amygdala-VMPFC connectivity in association with higher psychopathic traits.

The mirror neuron system in primates matches observations of actions with the motor representations used for their execution, and is a topic of intense research and debate in biological and computational disciplines. In robotics, models of this system have been used for enabling robots to imitate and learn how to perform tasks from human demonstrations. Yet, existing computational and robotic models of these systems are found in multiple levels of description, and although some models offer plausible explanations and testable predictions, the difference in the granularity of the experimental setups, methodologies, computational structures and selected modeled data make principled meta-analyses, common in other fields, difficult. In this paper, we adopt an interdisciplinary approach, using the BODB integrated environment in order to bring together several different but complementary computational models, by functionally decomposing them into brain operating principles (BOPs) which each capture a limited subset of the model's functionality. We then explore links from these BOPs to neuroimaging and neurophysiological data in order to pinpoint complementary and conflicting explanations and compare predictions against selected sets of neurobiological data. The results of this comparison are used to interpret mirror system neuroimaging results in terms of neural network activity, evaluate the biological plausibility of mirror system models, and suggest new experiments that can shed light on the neural basis of mirror systems.

How does witnessing a hateful person in pain compare to witnessing a likable person in pain? The current study compared the brain bases for how we perceive likable people in pain with those of viewing hateful people in pain. While social bonds are built through sharing the plight and pain of others in the name of empathy, viewing a hateful person in pain also has many potential ramifications. In this functional Magnetic Resonance Imaging (fMRI) study, Caucasian Jewish male participants viewed videos of (1) disliked, hateful, anti-Semitic individuals, and (2) liked, non-hateful, tolerant individuals in pain. The results showed that, compared with viewing liked people, viewing hateful people in pain elicited increased responses in regions associated with observation of physical pain (the insular cortex, the anterior cingulate cortex (ACC), and the somatosensory cortex), reward processing (the striatum), and frontal regions associated with emotion regulation. Functional connectivity analyses revealed connections between seed regions in the left ACC and right insular cortex with reward regions, the amygdala, and frontal regions associated with emotion regulation. These data indicate that regions of the brain active while viewing someone in pain may be more active in response to the danger or threat posed by witnessing the pain of a hateful individual more so than the desire to empathize with a likable person's pain.

Our experiences with others affect how we perceive their actions. In particular, activity in bilateral premotor and parietal cortices during action observation, collectively known as the action observation network (AON), is modulated by one's expertise with the observed actions or individuals. However, conflicting reports suggest that AON activity is greatest both for familiar and unfamiliar actions. The current study examines the effects of different types and amounts of experience (e.g., visual, interpersonal, personal) on AON activation. fMRI was used to scan 16 healthy participants without prior experience with individuals with amputations (novices), 11 experienced occupational therapists (OTs) who had varying amounts of experience with individuals with amputations, and one individual born with below-elbow residual limbs (participant CJ), as they viewed video clips of goal-matched actions performed by an individual with residual limbs and by an individual with hands. Participants were given increased visual exposure to actions performed by both effectors midway through the scanning procedure. Novices demonstrated a large AON response to the initial viewing of an individual with residual limbs compared to one with hands, but this signal was attenuated after they received visual exposure to both effectors. In contrast, OTs, who had moderate familiarity with residual limbs, demonstrated a lower AON response upon initial viewing-similar to novices after they received visual exposure. At the other extreme, CJ, who has extreme familiarity with residual limbs both visually and motorically, shows a largely increased left-lateralized AON response, exceeding that of novices and experienced OTs, when viewing the residual limb compared to hand actions. These results suggest that a nuanced model of AON engagement is needed to explain how cases of both extreme experience (CJ) and extreme novelty (novices) can result in the greatest AON activity.

Background and Purpose. Much recent interest surrounds the use of action observation, which is observing another individual performing a motor task, in stroke rehabilitation, to promote motor recovery by engaging similar brain regions to action execution. This may be especially useful in individuals with limited mobility. Here, we assess how cortical motor activity during action observation is affected by stroke and by stroke-related motor deficits.

Methods. We used functional MRI to compare brain activity during right and left hand action observation in right-handed nondisabled participants and participants who were right-handed before left hemisphere stroke. All participants performed the same actions after their functional MRI.

Results. Nondisabled participants show greater bilateral cortical motor activity when observing actions made using the left hand, whereas participants with stroke show greater ipsilesional cortical motor activity when observing actions made using the right (paretic) hand (P<0.05; corrected). For both groups, action processing is modulated by motor capability: cortical motor activity is greater when observing the hand with lower motor scores (P<0.05; corrected). Furthermore, for stroke, the extent of ipsilesional activity correlates with lesion volume (P=0.049), in a pattern that suggests adaptive plasticity.

Conclusions. We found that action observation activates specific motor plans in damaged motor circuits after stroke, and this activity is related to motor capability to perform the same actions. Cortical motor activity during action observation may be relevant to motor learning, and to motor relearning in stroke rehabilitation.

Although creativity has been called the most important of all human resources, its neural basis is still unclear. In the current study, we used fMRI to measure neural activity in participants solving a visuospatial creativity problem that involves divergent thinking and has been considered a canonical right hemisphere task. As hypothesized, both the visual creativity task and the control task as compared to rest activated a variety of areas including the posterior parietal cortex bilaterally and motor regions, which are known to be involved in visuospatial rotation of objects. However, directly comparing the two tasks indicated that the creative task more strongly activated left hemisphere regions including the posterior parietal cortex, the premotor cortex, dorsolateral prefrontal cortex (DLPFC) and the medial PFC. These results demonstrate that even in a task that is specialized to the right hemisphere, robust parallel activity in the left hemisphere supports creative processing. Furthermore, the results support the notion that higher motor planning may be a general component of creative improvisation and that such goal-directed planning of novel solutions may be organized top-down by the left DLPFC and by working memory processing in the medial prefrontal cortex.

Observing actions performed by others engages one's own sensorimotor regions, typically with greater activity for actions within one's own motor abilities or for which one has prior experience. However, it is unclear how experience modulates the neural response during the observation of impossible actions, beyond one's own abilities. Using fMRI, we scanned typically-developed participants as they observed actions performed by a novel biological effector (the residual limb of a woman born without arms) and a familiar biological effector (a hand). Participants initially demonstrated greater activity in the bilateral inferior and superior parietal cortices when observing actions made by the residual limb compared to the hand, with more empathic participants activating the right inferior parietal lobule, corresponding to the posterior component of the action observation network, more strongly. Activity in the parietal regions may indicate matching the kinematics of a novel effector to one's own existing sensorimotor system, a process that may be more active in more empathic individuals. Participants then received extended visual exposure to each effector, after which they showed little difference between activation in response to residual limb compared to hand actions, only in the right superior parietal lobule. This suggests that visual experience may attenuate the difference between how residual limb and hand actions are represented using one's own body representations, allowing us to flexibly map physically different others onto our own body representations.

The human putative mirror neuron system (MNS) is a key network hypothesized to play a role in many social cognitive and language-related abilities. This chapter begins by discussing basic findings on the mirror system, which encompasses motor-related brain regions that fire when an individual both performs and observes others perform actions. We then discuss how these shared action/observation regions are thought to underlie one’s ability to understand others via simulation of their actions onto one’s own motor representations. Finally, we conclude by noting how the frontal mirror region coincides with Broca’s area, a language region in the brain, leading some to propose that the MNS may also play a role in language and gesture abilities.

Observing someone perform an action engages brain regions involved in motor planning, such as the inferior frontal, premotor, and inferior parietal cortices. Recent research suggests that during action observation, activity in these neural regions can be modulated by membership in an ethnic group defined by physical differences. In this study we expanded upon previous research by matching physical similarity of two different social groups and investigating whether likability of an outgroup member modulates activity in neural regions involved in action observation. Seventeen Jewish subjects were familiarized with biographies of eight individuals, half of the individuals belonged to Neo-Nazi groups (dislikable) and half of which did not (likable). All subjects and actors in the stimuli were Caucasian and physically similar. The subjects then viewed videos of actors portraying the characters performing simple motor actions (e.g. grasping a water bottle and raising it to the lips), while undergoing fMRI. Using multivariate pattern analysis (MVPA), we found that a classifier trained on brain activation patterns successfully discriminated between the likable and dislikable action observation conditions within the right ventral premotor cortex. These data indicate that the spatial pattern of activity in action observation related neural regions is modulated by likability even when watching a simple action such as reaching for a cup. These findings lend further support for the notion that social factors such as interpersonal liking modulate perceptual processing in motor-related cortices.

Occupational therapy has traditionally championed the use of meaningful occupations in rehabilitation. Emerging research in neuroscience about the putative human mirror neuron system may provide empirical support for the use of occupations to improve outcomes in rehabilitation. This article provides an interdisciplinary framework for understanding the mirror neuron system — a network of motor-related brain regions activated during the production and perception of the same actions — in relation to occupational therapy. The authors present an overview of recent research on the mirror neuron system, highlighting features that are relevant to clinical practice in occupational therapy. They also discuss the potential use of the mirror neuron system in motor rehabilitation and how it may be deficient in populations served by occupational therapy, including individuals with dyspraxia, multisensory integration disorders, and social interaction difficulties. Methods are proposed for occupational therapy to translate these neuroscience findings on the mirror neuron system into clinical applications and the authors suggest that future research in neuroscience would benefit from integrating the occupational therapy perspective.

How do we understand and empathize with individuals whose bodies are drastically different from our own? We investigated the neural processes by which an individual with a radically different body, a congenital amputee who is born without limbs, engages her own sensory-motor representations as a means to understand other people’s body actions or emotional states. Our results support the prediction that when the goal of the action is possible for the observer, one’s own motor regions are involved in processing action observation, just as when individuals viewed those similar to themselves. However, when the observed actions are not possible, mentalizing mechanisms, relying on a different set of neural structures, are additionally recruited to process the actions. Furthermore, our results indicate that when individuals view others experiencing pain in body parts that they have, the insula and somatosensory cortices are activated, consistent with previous reports. However, when an individual views others experiencing pain in body parts that she does not have, the insula and secondary somatosensory cortices are still active, but the primary somatosensory cortices are not. These results provide a novel understanding for how we understand and empathize with individuals who drastically differ from the self.

Recent research suggests that the inference of others' intentions from their observed actions is supported by two neural systems that perform complementary roles. The human putative mirror neuron system (pMNS) is thought to support automatic motor simulations of observed actions, with increased activity for previously experienced actions, whereas the mentalizing system provides reflective, non-intuitive reasoning of others' perspectives, particularly in the absence of prior experience. In the current fMRI study, we show how motor familiarity with an action and perceptual familiarity with the race of an actor uniquely modulate these two systems. Chinese participants were asked to infer the intentions of actors performing symbolic gestures, an important form of non-verbal communication that has been shown to activate both mentalizing and mirror neuron regions. Stimuli were manipulated along two dimensions: (1) actor's race (Caucasian vs. Chinese actors) and (2) participants' level of experience with the gestures (familiar or unfamiliar). We found that observing all gestures compared to observing still images was associated with increased activity in key regions of both the pMNS and mentalizing systems. In addition, observations of one's same race generated greater activity in the posterior pMNS-related regions and the insula than observations of a different race. Surprisingly, however, familiar gestures more strongly activated regions associated with mentalizing, while unfamiliar gestures more strongly activated the posterior region of the pMNS, a finding that is contrary to prior literature and demonstrates the powerful modulatory effects of both motor and perceptual familiarity on pMNS and mentalizing regions when asked to infer the intentions of intransitive gestures.

Language is a dominant part of our daily activities, playing a significant role in narrating our actions and mediating our interactions with one another. In this article, we examine emerging neuroscientific evidence that language is biologically linked to action and suggest that studying language from an occupation-based perspective can contribute a rich dimension of analysis for occupational science. We briefly review several of the ways in which language is currently being incorporated into the study of occupations and conclude by suggesting future directions for an occupation-based study of language.

Human adults typically respond faster to their own face than to the faces of others. However, in Chinese participants, this self-face advantage is lost in the presence of one's supervisor, and they respond faster to their supervisor's face than to their own. While this “boss effect” suggests a strong modulation of self-processing in the presence of influential social superiors, the current study examined whether this effect was true across cultures. Given the wealth of literature on cultural differences between collectivist, interdependent versus individualistic, independent self-construals, we hypothesized that the boss effect might be weaker in independent than interdependent cultures. Twenty European American college students were asked to identify orientations of their own face or their supervisors' face. We found that European Americans, unlike Chinese participants, did not show a “boss effect” and maintained the self-face advantage even in the presence of their supervisor's face. Interestingly, however, their self-face advantage decreased as their ratings of their boss's perceived social status increased, suggesting that self-processing in Americans is influenced more by one's social status than by one's hierarchical position as a social superior. In addition, when their boss's face was presented with a labmate's face, American participants responded faster to the boss's face, indicating that the boss may represent general social dominance rather than a direct negative threat to oneself, in more independent cultures. Altogether, these results demonstrate a strong cultural modulation of self-processing in social contexts and suggest that the very concept of social positions, such as a boss, may hold markedly different meanings to the self across Western and East Asian cultures.

Body Integrity Identity Disorder (BIID) is a condition in which people generally desire amputation of healthy limbs but can also desire paralysis, blindness, or other disabilities. The current study explored the demographics and experiences of individuals with this condition with specific attention to perceived physical differences of the affected limbs. Participants were recruited from three BIID-focused Internet forums to participate in two online surveys. There were 97 unique participants total, the largest sample size of individuals with BIID to date. It was found that individuals with BIID differ from the normal population in handedness and sexual orientation. Participants who reported differences in sensation in the affected limb(s) were also significantly more likely to report difficulty in learning/imitation, difference of feeling during use, and difference in performance of the affected limb(s). Furthermore it was found that individuals who achieved amputation almost always experienced phantom limbs and that many participants choose to use prosthetics post-amputation. These results shed light on the many facets of BIID and the perception of self and body schema. Future studies using neuroimaging may be able to better understand the neural bases of BIID.

Keywords: Body Integrity Identity Disorder, superior parietal lobule, forward model, inverse model, apotemnophilia

We examined the effect of linguistic comprehension on early perceptual encoding in a series of electrophysiological and behavioral studies on humans. Using the fact that pictures of faces elicit a robust and reliable evoked response that peaks at ∼170 ms after stimulus onset (N170), we measured the N170 to faces that were preceded by primes that referred to either faces or scenes. When the primes were auditory sentences, the magnitude of the N170 was larger when the face stimuli were preceded by sentences describing faces compared to sentences describing scenes. In contrast, when the primes were visual, the N170 was smaller after visual primes of faces compared to visual primes of scenes. Similar opposing effects of linguistic and visual primes were also observed in a reaction time experiment in which participants judged the gender of faces. These results provide novel evidence of the influence of language on early perceptual processes and suggest a surprising mechanistic description of this interaction: linguistic primes produce content-specific interference on subsequent visual processing. This interference may be a consequence of the natural statistics of language and vision given that linguistic content is generally uncorrelated with the contents of perception.

Background. The posteromedial cortex (PMC) and medial prefrontal cortex (mPFC) are part of a network of brain regions that has been found to exhibit decreased activity during goal-oriented tasks. This network is thought to support a baseline of brain activity, and is commonly referred to as the “default network”. Although recent reports suggest that the PMC and mPFC are associated with affective, social, and self-referential processes, the relationship between these default network components and personality traits, especially those pertaining to social context, is poorly understood.

Methodology/Principal Findings. In the current investigation, we assessed the relationship between PMC and mPFC deactivations and psychopathic personality traits using fMRI and a self-report measure. We found that PMC deactivations predicted traits related to egocentricity and mPFC deactivations predicted traits related to decision-making.

Conclusions/Significance. These results suggest that the PMC and mPFC are associated with processes involving self-relevancy and affective decision-making, consistent with previous reports. More generally, these findings suggest a link between default network activity and personality traits.

Mirror neurons found in the premotor and parietal cortex respond not only during action execution, but also during observation of actions being performed by others. Thus, the motor system may be activated without overt movement. Rehabilitation of motor function after stroke is often challenging due to severity of impairment and poor to absent voluntary movement ability. Methods in stroke rehabilitation based on the mirror neuron system—action observation, motor imagery, and imitation—take advantage of this opportunity to rebuild motor function despite impairments, as an alternative or complement to physical therapy. Here the authors review research into each condition of practice, and discuss the relevance of the mirror neuron system to stroke recovery.

Background. Prosody, the melody and intonation of speech, involves the rhythm, rate, pitch and voice quality to relay linguistic and emotional information from one individual to another. A significant component of human social communication depends upon interpreting and responding to another person’s prosodic tone as well as one’s own ability to produce prosodic speech. However there has been little work on whether the perception and production of prosody share common neural processes, and if so, how these might correlate with individual differences in social ability.

Methods. The aim of the present study was to determine the degree to which perception and production of prosody rely on shared neural systems. Using fMRI, neural activity during perception and production of a meaningless phrase in different prosodic intonations was measured. Regions of overlap for production and perception of prosody were found in premotor regions, in particular the left inferior frontal gyrus (IFG). Activity in these regions was further found to correlate with how high an individual scored on two different measures of affective empathy as well as a measure on prosodic production ability.

Conclusions. These data indicate, for the first time, that areas that are important for prosody production may also be utilized for prosody perception, as well as other aspects of social communication and social understanding, such as aspects of empathy and prosodic ability.

What are the neural correlates of insight solutions? To explore this question we asked participants to perform an anagram task while in the fMRI scanner. Previous research indicates that anagrams are unique in that they can yield both insight and search solutions in expert subjects. Using a single-trial fMRI paradigm, we utilized the anagram methodology to explore the neural correlates of insight versus search solutions. We used both reaction time measures and subjective reports to classify each trial as a search or insight solution. Data indicate that verbal insight solutions activate a distributed neural network that includes bilateral activation in the insula, the right prefrontal cortex, and the anterior cingulate. These areas are discussed with their possible role in evaluation and metacognition of insight solutions, as well as attention and monitoring during insight.

Mirror neurons are defined as neurons in the monkey cortex which respond to goal oriented actions, whether the behavior is self-generated or produced by another. Here we briefly review this literature and consider evidence from behavioral, neuropsychological, and brain imaging studies for a similar mirror neuron system in humans. Furthermore, we review functions of this system related to action comprehension and motor imagery, as well as evidence for speculations on the system's ties with conceptual knowledge and language.

There is evidence that the right hemisphere is involved in processing self-related stimuli. Previous brain imaging research has found a network of right-lateralized brain regions that preferentially respond to seeing one's own face rather than a familiar other. Given that the self is an abstract multimodal concept, we tested whether these brain regions would also discriminate the sound of one's own voice compared to a friend's voice. Participants were shown photographs of their own face and friend's face, and also listened to recordings of their own voice and a friend's voice during fMRI scanning. Consistent with previous studies, seeing one's own face activated regions in the inferior frontal gyrus (IFG), inferior parietal lobe and inferior occipital cortex in the right hemisphere. In addition, listening to one's voice also showed increased activity in the right IFG. These data suggest that the right IFG is concerned with processing self-related stimuli across multiple sensory modalities and that it may contribute to an abstract self-representation.

The theory of embodied semantics for actions specifies that the sensory-motor areas used for producing an action are also used for the conceptual representation of the same action. Here we review the functional imaging literature that has explored this theory and consider both supporting as well as challenging fMRI findings. In particular we address the representation of actions and concepts as well as literal and metaphorical phrases in the premotor cortex.

Mirror neurons are defined as neurons in the monkey cortex which respond to goal oriented actions, whether the behavior is self-generated or produced by another. Here we briefly review this literature and consider evidence from behavioral, neuropsychological, and brain imaging studies for a similar mirror neuron system in humans. Furthermore, we review functions of this system related to action comprehension and motor imagery, as well as evidence for speculations on the system’s ties with conceptual knowledge and language.

Does sentence comprehension related to faces modulate activity in the fusiform face area (FFA) and does sentence comprehension related to places modulate activity in the parahippocampal place area (PPA)? We investigated this question in an fMRI experiment. Participants listened to sentences describing faces, places, or objects, with the latter serving as a control condition. In a separate run, we localized the FFA and PPA in each participant using a perceptual task. We observed a significant interaction between the region of interest (FFA vs. PPA) and sentence type (face vs. place). Activity in the left FFA was modulated by face sentences and in the left PPA was modulated by place sentences. Surprisingly, activation in each region of interest was reduced when listening to sentences requiring semantic analysis related to that region's domain specificity. No modulation was found in the corresponding right hemisphere ROIs. We conclude that processing sentences may involve inhibition of some visual processing areas in a content-specific manner. Furthermore, our data indicate that this semantic-based modulation is restricted to the left hemisphere. We discuss how these results may constrain neural models of embodied semantics.

How do we understand the actions of other individuals if we can only hear them? Auditory mirror neurons respond both while monkeys perform hand or mouth actions and while they listen to sounds of similar actions. This system might be critical for auditory action understanding and language evolution. Preliminary evidence suggests that a similar system may exist in humans. Using fMRI, we searched for brain areas that respond both during motor execution and when individuals listened to the sound of an action made by the same effector. We show that a left hemispheric temporo-parieto-premotor circuit is activated in both cases, providing evidence for a human auditory mirror system. In the left premotor cortex, a somatotopic pattern of activation was also observed: A dorsal cluster was more involved during listening and execution of hand actions, and a ventral cluster was more involved during listening and execution of mouth actions. Most of this system appears to be multimodal because it also responds to the sight of similar actions. Finally, individuals who scored higher on an empathy scale activated this system more strongly, adding evidence for a possible link between the motor mirror system and empathy.

The thesis of embodied semantics holds that conceptual representations accessed during linguistic processing are, in part, equivalent to the sensory-motor representations required for the enactment of the concepts described. Here, using fMRI, we tested the hypothesis that areas in human premotor cortex that respond both to the execution and observation of actions — mirror neuron areas — are key neural structures in these processes. Participants observed actions and read phrases relating to foot, hand, or mouth actions. In the premotor cortex of the left hemisphere, a clear congruence was found between effector-specific activations of visually presented actions and of actions described by literal phrases. These results suggest a key role of mirror neuron areas in the re-enactment of sensory-motor representations during conceptual processing of actions invoked by linguistic stimuli.

A cortical network consisting of the inferior frontal, rostral inferior parietal, and posterior superior temporal cortices has been implicated in representing actions in the primate brain and is critical to imitation in humans. This neural circuitry may be an evolutionary precursor of neural systems associated with language. However, language is predominantly lateralized to the left hemisphere, whereas the degree of lateralization of the imitation circuitry in humans is unclear. We conducted a functional magnetic resonance imaging study of imitation of finger movements with lateralized stimuli and responses. During imitation, activity in the inferior frontal and rostral inferior parietal cortex, although fairly bilateral, was stronger in the hemisphere ipsilateral to the visual stimulus and response hand. This ipsilateral pattern is at variance with the typical contralateral activity of primary visual and motor areas. Reliably increased signal in the right superior temporal sulcus (STS) was observed for both left-sided and right-sided imitation tasks, although subthreshold activity was also observed in the left STS. Overall, the data indicate that visual and motor components of the human mirror system are not left-lateralized. The left hemisphere superiority for language, then, must be have been favored by other types of language precursors, perhaps auditory or multimodal action representations.

Previous research indicates that people respond fastest when the motor response is (spatially, functionally, anatomically, or otherwise) congruent to the visual stimulus. This effect, called ideomotor compatibility, is thought to be expressed in motor areas. Congruence occurs when the stimulus and response share some dimensions in their internal representations. If the ideomotor compatibility hypothesis were true, we would expect facilitation when right hand stimuli are presented to the left hemisphere, or left hand stimuli are presented to the right hemisphere. To address this issue, we conducted a simple reaction time experiment with lateralized targets. Participants were instructed to press a button as soon as a target was observed. The target stimulus was a left hand, a right hand, or a neutral control. Each hemisphere showed faster responses to contralateral hand stimuli as compared with ipsilateral hand stimuli, consistent with the ideomotor compatibility hypothesis. The results support an automatic and implicit processing of visual stimuli within motor representations even when no recognition of, or decision about, the stimulus is necessary.

Blocking the capacity to speak aloud (overt speech arrest, SA) may be induced by repetitive transcranial magnetic stimulation (rTMS). The possibility, however, of blocking internal speech (covert SA) has not been explored. To investigate this issue, we conducted two rTMS experiments. In the first experiment, we stimulated two left frontal lobe sites. The first was a motor site (left posterior site) and the second was a nonmotor site located in correspondence to the posterior part of the inferior frontal gyrus (IFG) (left anterior site). The corresponding right hemisphere nonmotor SA site was stimulated as a control. In the second experiment, we focused on the right hemisphere and stimulated a right hemisphere motor site (right posterior site), and, as control sites, a right hemisphere nonmotor site corresponding to the IFG (right anterior site) and a left hemisphere anteromedial site (left control). For both experiments, participants performed a syllable counting task both covertly and overtly for each stimulation site. Longer latencies in this task imply the occurrence of an overt and/or covert SA.

All participants showed significantly longer latencies when stimulation was either over the left posterior or the left anterior site, as compared with the right hemisphere site (Experiment 1). This result was observed for the overt and covert speech task alike. During stimulation of the posterior right hemisphere site, a dissociation for overt and covert speech was observed. An overt SA was observed but there was no evidence for a covert SA (Experiment 2). Taken together, the results show that rTMS can induce a covert SA when applied to areas over the brain that are pertinent to language. Furthermore, both the left posterior/motor site and the left anterior/IFG site appear to be essential to language elaboration even when motor output is not required.

Previous studies indicate that the motor areas of both hemispheres are active when observing actions. Here we explored how the motor areas of each hemisphere respond to the sounds associated with actions. We used transcranial magnetic stimulation (TMS) to measure motor corticospinal excitability of hand muscles while listening to sounds. Sounds associated with bimanual actions produced greater motor corticospinal excitability than sounds associated with leg movements or control sounds. This facilitation was exclusively lateralized to the left hemisphere, the dominant hemisphere for language. These results are consistent with the hypothesis that action coding may be a precursor of language.

Action observation facilitates corticospinal excitability. This is presumably due to a premotor neural system that is active when we perform actions and when we observe actions performed by others. It has been speculated that this neural system is a precursor of neural systems subserving language. If this theory is true, we may expect hemispheric differences in the motor facilitation produced by action observation, with the language-dominant left hemisphere showing stronger facilitation than the right hemisphere. Furthermore, it has been suggested that body parts are recognized via cortical regions controlling sensory and motor processing associated with that body part. If this is true, then corticospinal facilitation during action observation should be modulated by the laterality of the observed body part. The present study addressed these two issues using TMS for each motor cortex separately as participants observed actions being performed by a left hand, a right hand, or a control stimulus on the computer screen. We found no overall difference between the right and left hemisphere for motor-evoked potential (MEP) size during action observation. However, when TMS was applied to the left motor cortex, MEPs were larger while observing right hand actions. Likewise, when TMS was applied to the right motor cortex, MEPs were larger while observing left hand actions. Our data do not suggest left hemisphere superiority in the facilitating effects of action observation on the motor system. However, they do support the notion of a sensory-motor loop according to which sensory stimulus properties (for example, the image of a left hand or a right hand) directly affect motor cortex activity, even when no motor output is required. The pattern of this effect is congruent with the pattern of motor representation in each hemisphere.