University of Southern California
University of Southern California
Mrs. T.H. Chan Division of Occupational Science and Occupational Therapy
Mrs. T.H. Chan Division of Occupational Science and Occupational Therapy
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Sook-Lei Liew PhD, OTR/L

Sook-Lei Liew

Assistant Professor, joint appointments with the USC Division of Biokinesiology and Physical Therapy and the Keck School of Medicine of USC, Department of Neurology

Room: CHP 101G
(323) 442-0315
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Dr. Sook-Lei Liew completed her undergraduate education at Rice University where she earned bachelor's degrees in Kinesiology (with a concentration in Sports Medicine) and English. She received her Master of Arts degree in Occupational Therapy from the University of Southern California with a focus on adult rehabilitation. She remained at USC and completed her PhD in Occupational Science (with a concentration in Cognitive Neuroscience) investigating, with her advisor Dr. Lisa Aziz-Zadeh, experience-dependent changes in the motor system during action observation using neuroimaging and behavioral methods.
From 2012 to 2014, Dr. Liew was a Postdoctoral Fellow at the National Institute of Neurological Disorders and Stroke at the NIH under the guidance of Dr. Leonardo Cohen, where she studied mechanisms of neural plasticity and neural repair using noninvasive brain stimulation and brain-computer interfaces, specifically, real-time fMRI neurofeedback. During her postdoctoral fellowship, Dr. Liew also completed collaborations at the University of Tübingen (with Drs. Niels Birbaumer and Surjo Soekadar) and at Johns Hopkins School of Medicine (with Dr. Pablo Celnik) to examine the use of brain-computer interfaces with stroke patients and noninvasive brain stimulation to enhance motor learning in healthy individuals, respectively. She joined the USC Chan Division in January 2015.

Research Interests

Stroke is one of the leading causes of serious long-term adult disability around the world. Despite intensive physical and occupational therapy, many stroke survivors are unable to independently care for themselves due to persistent motor, cognitive and communicative difficulties. Large variations in lesion damage and individual characteristics (such as age, gender, physical fitness and genetic makeup) make stroke rehabilitation outcomes difficult to predict. Novel methods that predict and maximize each individual's potential for recovery after stroke are thus desperately needed.
The goals of the Neural Plasticity and Neurorehabilitation Laboratory, under the direction of Dr. Sook-Lei Liew, are: 1.) to characterize and predict neural plasticity changes in healthy individuals and in individuals after stroke throughout the process of learning or recovery; 2.) to enhance neural plasticity or neural recovery in individuals using noninvasive brain stimulation, brain-computer interfaces and novel learning paradigms; and 3.) to personalize the use of plasticity-inducing paradigms in order to capitalize on each individual's unique learning or recovery potential. These goals support the overall mission of the laboratory, which is to enhance neural plasticity in a wide population of individuals in order to improve their quality of life and engagement in meaningful activities.


Postdoctoral Fellow in Human Cortical Physiology and Neurorehabilitation
2014 | National Institute of Neurological Disorders and Stroke, National Institutes of Health

Doctor of Philosophy (PhD) in Occupational Science (Cognitive Neuroscience concentration)
2012 | University of Southern California

Master of Arts (MA) in Occupational Therapy
2008 | University of Southern California

Bachelor of Arts (BA) in Kinesiology (Sports Medicine concentration)
2006 | Rice University

Bachelor of Arts (BA) in English
2006 | Rice University


Book Chapters

Liew, S. L., & Aziz-Zadeh, L. S. (2013). The human mirror neuron system, social control, and language. In D. D. Franks & J. H. Turner (Eds.), Handbook of neurosociology (pp. 183-205). Dordrecht, The Netherlands: Springer. doi:10.1007/978-94-007-4473-8_14 Show abstractHide abstract

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.

Liew, S. L., & Aziz-Zadeh, L. S. (2011). The human mirror neuron system and social cognition. In R. P. Ebstein, S. Shamay-Tsoory, & S. H. Chew (Eds.), From DNA to social cognition (pp. 63-80). Hoboken, NJ: Wiley-Blackwell. doi:10.1002/9781118101803.ch4

Journal Articles

Anglin, J. M., Sugiyama, T., & Liew, S. L. (2017). Visuomotor adaptation in head-mounted virtual reality versus conventional training. Scientific Reports, 7, 45469. doi:10.1038/srep45469 Show abstractHide abstract

Immersive, head-mounted virtual reality (HMD-VR) provides a unique opportunity to understand how changes in sensory environments affect motor learning. However, potential differences in mechanisms of motor learning and adaptation in HMD-VR versus a conventional training (CT) environment have not been extensively explored. Here, we investigated whether adaptation on a visuomotor rotation task in HMD-VR yields similar adaptation effects in CT and whether these effects are achieved through similar mechanisms. Specifically, recent work has shown that visuomotor adaptation may occur via both an implicit, error-based internal model and a more cognitive, explicit strategic component. We sought to measure both overall adaptation and balance between implicit and explicit mechanisms in HMD-VR versus CT. Twenty-four healthy individuals were placed in either HMD-VR or CT and trained on an identical visuomotor adaptation task that measured both implicit and explicit components. Our results showed that the overall timecourse of adaption was similar in both HMD-VR and CT. However, HMD-VR participants utilized a greater cognitive strategy than CT, while CT participants engaged in greater implicit learning. These results suggest that while both conditions produce similar results in overall adaptation, the mechanisms by which visuomotor adaption occurs in HMD-VR appear to be more reliant on cognitive strategies.

Lefebvre, S., & Liew, S. L. (2017). Anatomical parameters of tDCS to modulate the motor system after stroke: A review. Frontiers in Neurology, 9, 29. doi:10.3389/fneur.2017.00029 Show abstractHide abstract

Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation method to modulate the local field potential in neural tissue and consequently, cortical excitability. As tDCS is relatively portable, affordable, and accessible, the applications of tDCS to probe brain-behavior connections have rapidly increased in the last 10?years. One of the most promising applications is the use of tDCS to modulate excitability in the motor cortex after stroke and promote motor recovery. However, the results of clinical studies implementing tDCS to modulate motor excitability have been highly variable, with some studies demonstrating that as many as 50% or more of patients fail to show a response to stimulation. Much effort has therefore been dedicated to understand the sources of variability affecting tDCS efficacy. Possible suspects include the placement of the electrodes, task parameters during stimulation, dosing (current amplitude, duration of stimulation, frequency of stimulation), individual states (e.g., anxiety, motivation, attention), and more. In this review, we first briefly review potential sources of variability specific to stroke motor recovery following tDCS. We then examine how the anatomical variability in tDCS placement [e.g., neural target(s) and montages employed] may alter the neuromodulatory effects that tDCS exerts on the post-stroke motor system.

Sainburg, R. L., Liew, S. L., Frey, S. H., & Clark, F. (2017). Promoting translational research among movement science, occupational science, and occupational therapy. Journal of Motor Behavior, 49, 1-7. doi:10.1080/00222895.2016.1271299 Show abstractHide abstract

Integration of research in the fields of neural control of movement and biomechanics (collectively referred to as movement science) with the field of human occupation directly benefits both areas of study. Specifically, incorporating many of the quantitative scientific methods and analyses employed in movement science can help accelerate the development of rehabilitation-relevant research in occupational therapy (OT) and occupational science (OS). Reciprocally, OT and OS, which focus on the performance of everyday activities (occupations) to promote health and well-being, provide theoretical frameworks to guide research on the performance of actions in the context of social, psychological, and environmental factors. Given both fields' mutual interest in the study of movement as it relates to health and disease, the authors posit that combining OS and OT theories and principles with the theories and methods in movement science may lead to new, impactful, and clinically relevant knowledge. The first step is to ensure that individuals with OS or OT backgrounds are academically prepared to pursue advanced study in movement science. In this article, the authors propose 2 strategies to address this need.

Sugiyama, T., & Liew, S. L. (2017). The effects of sensory manipulations on motor behavior: From basic science to clinical rehabilitation. Journal of Motor Behavior, 49, 67-77. doi:10.1080/00222895.2016.1241740 Show abstractHide abstract

Modifying sensory aspects of the learning environment can influence motor behavior. Although the effects of sensory manipulations on motor behavior have been widely studied, there still remains a great deal of variability across the field in terms of how sensory information has been manipulated or applied. Here, the authors briefly review and integrate the literature from each sensory modality to gain a better understanding of how sensory manipulations can best be used to enhance motor behavior. Then, they discuss 2 emerging themes from this literature that are important for translating sensory manipulation research into effective interventions. Finally, the authors provide future research directions that may lead to enhanced efficacy of sensory manipulations for motor learning and rehabilitation.

Sugiyama, T., & Liew, S. L. (2016). The effects of sensory manipulations on motor behavior: From basic science to clinical rehabilitation. Journal of Motor Behavior, 9, 1-11. Advance online publication. doi:10.1080/00222895.2016.1241740 Show abstractHide abstract

Modifying sensory aspects of the learning environment can influence motor behavior. Although the effects of sensory manipulations on motor behavior have been widely studied, there still remains a great deal of variability across the field in terms of how sensory information has been manipulated or applied. Here, the authors briefly review and integrate the literature from each sensory modality to gain a better understanding of how sensory manipulations can best be used to enhance motor behavior. Then, they discuss 2 emerging themes from this literature that are important for translating sensory manipulation research into effective interventions. Finally, the authors provide future research directions that may lead to enhanced efficacy of sensory manipulations for motor learning and rehabilitation.

Liew, S. L., Rana, M., Cornelsen, S., Fortunato de Barros Filho, M., Birbaumer, N., Sitaram, R., Cohen, L. G., & Soekadar, S. R. (2016). Improving motor corticothalamic communication after stroke using real-time fMRI connectivity-based neurofeedback. Neurorehabilitation and Neural Repair, 30, 671-675. doi:10.1177/1545968315619699 Show abstractHide abstract

BACKGROUND: Two thirds of stroke survivors experience motor impairment resulting in long-term disability. The anatomical substrate is often the disruption of cortico-subcortical pathways. It has been proposed that reestablishment of cortico-subcortical communication relates to functional recovery.
OBJECTIVE: In this study, we applied a novel training protocol to augment ipsilesional cortico-subcortical connectivity after stroke. Chronic stroke patients with severe motor impairment were provided online feedback of blood-oxygenation level dependent signal connectivity between cortical and subcortical regions critical for motor function using real-time functional magnetic resonance imaging neurofeedback.
RESULTS: In this proof of principle study, 3 out of 4 patients learned to voluntarily modulate cortico-subcortical connectivity as intended.
CONCLUSIONS: Our results document for the first time the feasibility and safety for patients with chronic stroke and severe motor impairment to self-regulate and augment ipsilesional cortico-subcortical connectivity through neurofeedback using real-time functional magnetic resonance imaging.

Craddock, R. C., Margulies, D. S., Bellec, P., Nichols, B. N., Alcauter, S., Barrios, F. A., Burnod, Y., Cannistraci, C. J., Cohen-Adad, J., De Leener, B., Dery, S., Downar, J., Dunlop, K., Franco, A. R., Froehlich, C. S., Gerber, A. J., Ghosh, S. S., Grabowski, T. J., Hill, S., Heinsfeld, A. S., Hutchison, R. M., Kundu, P., Laird, A. R., Liew, S., Lurie, D. J., McLaren, D. G., Meneguzzi, F., Mennes, M., Mesmoudi, S., O'Connor, D., Pasaye, E. H., Peltier, S., Poline, J., Prasad, G., Pereira, R. F., Quirion, P., Rokem, A., Saad, Z. S., Shi, Y., Strother, S. C., Toro, R., Uddin, L. Q., Van Horn, J. D., Van Meter, J. W., Welsh, R. C., & Xu, T. (2016). Brainhack: A collaborative workshop for the open neuroscience community. Gigascience, 5(1), 1-8. doi:10.1186/s13742-016-0121-x Show abstractHide abstract

Brainhack events offer a novel workshop format with participant-generated content that caters to the rapidly growing open neuroscience community. Including components from hackathons and unconferences, as well as parallel educational sessions, Brainhack fosters novel collaborations around the interests of its attendees. Here we provide an overview of its structure, past events, and example projects. Additionally, we outline current innovations such as regional events and post-conference publications. Through introducing Brainhack to the wider neuroscience community, we hope to provide a unique conference format that promotes the features of collaborative, open science.

Buch, E. R., Liew, S. L., & Cohen, L. G. (2016). Plasticity of sensorimotor networks: Multiple overlapping mechanisms. Neuroscientist. Advance online publication. doi:10.1177/1073858416638641 Show abstractHide abstract

Redundancy is an important feature of the motor system, as abundant degrees of freedom are prominent at every level of organization across the central and peripheral nervous systems, and musculoskeletal system. This basic feature results in a system that is both flexible and robust, and which can be sustainably adapted through plasticity mechanisms in response to intrinsic organismal changes and dynamic environments. While much early work of motor system organization has focused on synaptic-based plasticity processes that are driven via experience, recent investigations of neuron-glia interactions, epigenetic mechanisms and large-scale network dynamics have revealed a plethora of plasticity mechanisms that support motor system organization across multiple, overlapping spatial and temporal scales. Furthermore, an important role of these mechanisms is the regulation of intrinsic variability. Here, we review several of these mechanisms and discuss their potential role in neurorehabilitation.

Liew, S. L. (2014). Non-invasive brain stimulation in neurorehabilitation: Local and distant effects for motor recovery. Frontiers in Human Neuroscience, 8, 378. doi:10.3389/fnhum.2014.00378 Show abstractHide abstract

Non-invasive brain stimulation (NIBS) may enhance motor recovery after neurological injury through the causal induction of plasticity processes. Neurological injury, such as stroke, often results in serious long-term physical disabilities, and despite intensive therapy, a large majority of brain injury survivors fail to regain full motor function. Emerging research suggests that NIBS techniques, such as transcranial magnetic (TMS) and direct current (tDCS) stimulation, in association with customarily used neurorehabilitative treatments, may enhance motor recovery. This paper provides a general review on TMS and tDCS paradigms, the mechanisms by which they operate and the stimulation techniques used in neurorehabilitation, specifically stroke. TMS and tDCS influence regional neural activity underlying the stimulation location and also distant interconnected network activity throughout the brain. We discuss recent studies that document NIBS effects on global brain activity measured with various neuroimaging techniques, which help to characterize better strategies for more accurate NIBS stimulation. These rapidly growing areas of inquiry may hold potential for improving the effectiveness of NIBS-based interventions for clinical rehabilitation.

Liew, S. L., Agashe, H., Bhagat, N., Paek, A., & Bulea, T. C. (2013). A clinical roadmap for brain-neural machine interfaces: Trainees' perspectives on the 2013 International Workshop. IEEE Pulse, 4(5), 44-48. doi:10.1109/MPUL.2013.2271686 Show abstractHide abstract

Brain-neural machine interfaces (BNMIs) are systems that allow a user to control an artificial device, such as a computer cursor or a robotic limb, through imagined movements that are measured as neural activity. They provide the potential to restore mobility for those with motor deficiencies caused by stroke, spinal cord injury, or limb amputations. Such systems would have been considered a topic of science fiction a few decades ago but are now being increasingly developed in both research and industry. Workers in this area are charged with fabricating BNMIs that are safe, effective, easy to use, and affordable for clinical populations.

Liew, S. L., Sheng, T., Margetis, J. L., & Aziz-Zadeh, L. S. (2013). Both novelty and expertise increase action observation network activity. Frontiers in Human Neuroscience, 7, 541. doi:10.3389/fnhum.2013.00541 Show abstractHide abstract

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.

Aziz-Zadeh, L. S., Liew, S. L., & Dandekar, F. (2013). Exploring the neural correlates of visual creativity. Social Cognitive and Affective Neuroscience, 8, 475-480. doi:10.1093/scan/nss021 Show abstractHide abstract

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.

Liew, S. L., Sheng, T., & Aziz-Zadeh, L. S. (2013). Experience with an amputee modulates one’s own sensorimotor response during action observation. NeuroImage, 69, 138-145. doi:10.1016/j.neuroimage.2012.12.028 Show abstractHide abstract

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.

Liew, S. L., Garrison, K. A., Werner, J., & Aziz-Zadeh, L. S. (2012). The mirror neuron system: Innovations and implications for occupational therapy. OTJR: Occupation, Participation and Health, 32(3), 79-86. doi:10.3928/15394492-20111209-01 Show abstractHide abstract

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.

Aziz-Zadeh, L. S., Sheng, T., Liew, S. L., & Damasio, H. C. (2012). Understanding otherness: The neural bases of action comprehension and pain empathy in a congenital amputee. Cerebral Cortex, 22, 811-819. doi:10.1093/cercor/bhr139 Show abstractHide abstract

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.

Liew, S. L., & Aziz-Zadeh, L. S. (2011). The neuroscience of language and action in occupations: A review of findings from brain and behavioral sciences. Journal of Occupational Science, 18, 97-114. doi:10.1080/14427591.2011.575758 Show abstractHide abstract

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.

Liew, S. L., Ma, Y., Han, S., & Aziz-Zadeh, L. S. (2011). Who's afraid of the boss: Cultural differences in social hierarchies modulate self-face recognition in Chinese and Americans. PLoS ONE, 6(2), e16901. doi:10.1371/journal.pone.0016901 Show abstractHide abstract

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.

Liew, S. L., Han, S., & Aziz-Zadeh, L. S. (2011). Familiarity modulates mirror neuron and mentalizing regions during intention understanding. Human Brain Mapping, 32, 1986-1997. doi:10.1002/hbm.21164 Show abstractHide abstract

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.