University of Southern California
Mrs T.H. Chan Division of Occupational Science and Occupational Therapy
Neural Plasticity and Neurorehabilitation Laboratory | Publications

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Journal Articles

Liew, S.-L., Schmaal, L., & Jahanshad, N. (2019). Editorial: Collaborative efforts for understanding the human brain. Frontiers in Neuroinformatics, 13, 38.

Santarnecchi, E., Sprugnoli, G., Bricolo, E., Costantini, G., Liew, S.-L., Musaeus, C. S., Salvi, C., Pascual-Leone, A., Rossi, A., & Rossi, S. (2019). Gamma tACS over the temporal lobe increases the occurrence of Eureka! moments. Scientific Reports, 9, 5778. Show abstractHide abstract

The solution to a problem might manifest itself as a burst of unexpected, unpredictable clarity. Such Eureka! events, or Insight moments, are among the most fascinating mysteries of human cognition, whose neurophysiological substrate seems to include a role for oscillatory activity within the α and γ bands in the right parietal and temporal brain regions. We tested this hypothesis on thirty-one healthy participants using transcranial Alternating Current Stimulation (tACS) to externally amplify α (10 Hz) and γ (40 Hz) activity in the right parietal and temporal lobes, respectively. During γ-tACS over the right temporal lobe, we observed an increase in accuracy on a verbal insight task. Furthermore, electroencephalography (EEG) data revealed an increase in γ spectral power over bilateral temporal lobes after stimulation. Additionally, resting-state functional MRI data acquired before the stimulation session suggested a correlation between behavioral response to right temporal lobe tACS and functional connectivity of bilateral temporal lobes, in line with the bilateral increase in γ band revealed by EEG. Overall, results suggest the possibility of enhancing the probability of generating Eureka! moments in humans by means of frequency-specific noninvasive brain stimulation.


Journal Articles

Liew, S.-L., Anglin, J. M., Banks, N. W., Sondag, M., Ito, K. L., Kim, H., Chan, J., Ito, J., Jung, C., Khoshab, N., Lefebvre, S., Nakamura, W., Saldana, D., Schmiesing, A., Tran, C., Vo, D., Ard, T., Heydari, P., Kim, B., Aziz-Zadeh, L., Cramer, S. C., Liu, J., Soekadar, S., Nordvik, J.-E., Westlye, L. T., Wang, J., Winstein, C., Yu, C., Ai, L., Koo, B., Craddock, R. C., Milham, M., Lakich, M., Pienta, A., & Stroud, A. (2018). A large, open source dataset of stroke anatomical brain images and manual lesion segmentations. Scientific Data, 5, 180011. Show abstractHide abstract

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.

Ito, K. L., Kumar, A., Zavaliangos-Petropulu, A., Cramer, S. C., & Liew, S.-L. (2018). Pipeline for Analyzing Lesions After Stroke (PALS). Frontiers in Neuroinformatics, 12, 63. Show abstractHide abstract

Lesion analyses are critical for drawing insights about stroke injury and recovery, and their importance is underscored by growing efforts to collect and combine stroke neuroimaging data across research sites. However, while there are numerous processing pipelines for neuroimaging data in general, few can be smoothly applied to stroke data due to complications analyzing the lesioned region. As researchers often use their own tools or manual methods for stroke MRI analysis, this could lead to greater errors and difficulty replicating findings over time and across sites. Rigorous analysis protocols and quality control pipelines are thus urgently needed for stroke neuroimaging. To this end, we created the Pipeline for Analyzing Lesions after Stroke (PALS; DOI:, a scalable and user-friendly toolbox to facilitate and ensure quality in stroke research using T1-weighted MRIs. The PALS toolbox offers four modules integrated into a single pipeline, including (1) reorientation to radiological convention, (2) lesion correction for healthy white matter voxels, (3) lesion load calculation, and (4) visual quality control. In the present paper, we discuss each module and provide validation and example cases of our toolbox using multi-site data. Importantly, we also show that lesion correction with PALS significantly improves similarity between manual lesion segmentations by different tracers (z=3.43, p=0.0018). PALS can be found online at Future work will expand the PALS capabilities to include multimodal stroke imaging. We hope PALS will be a useful tool for the stroke neuroimaging community and foster new clinical insights.

Dayan, E., López-Alonso, V., Liew, S.-L., & Cohen, L. G. (2018). Distributed cortical structural properties contribute to motor cortical excitability and inhibition. Brain Structure and Function, 223(8), 3801–3812. Show abstractHide abstract

The link between the local structure of the primary motor cortex and motor function has been well documented. However, motor function relies on a network of interconnected brain regions and the link between the structural properties characterizing these distributed brain networks and motor function remains poorly understood. Here, we examined whether distributed patterns of brain structure, extending beyond the primary motor cortex can help classify two forms of motor function: corticospinal excitability and intracortical inhibition. To this effect, we recorded high-resolution structural magnetic resonance imaging scans in 25 healthy volunteers. To measure corticospinal excitability and inhibition in the same volunteers, we recorded motor evoked potentials (MEPs) elicited by single-pulse transcranial magnetic stimulation and short-interval intracortical inhibition (SICI) in a separate session. Support vector machine (SVM) pattern classification was used to identify distributed multi-voxel gray-matter areas, which distinguished subjects who had lower and higher MEPs and SICIs. We found that MEP and SICI classification could be predicted based on a widely distributed, largely non-overlapping pattern of voxels in frontal, parietal, temporal, occipital, and cerebellar regions. Thus, structural properties distributed over the brain beyond the primary motor cortex relate to motor function.
Cortical excitability; Cortical inhibition; TMS; MRI

Liew, S.-L., Thompson, T., Ramirez, J., Butcher, P., Taylor, J. A., & Celnik, P. A. (2018). Variable neural contributions to explicit and implicit learning during visuomotor adaptation. Frontiers in Neuroscience, 12, 610. Show abstractHide abstract

We routinely make fine motor adjustments to maintain optimal motor performance. These adaptations have been attributed to both implicit, error-based mechanisms, and explicit, strategy-based mechanisms. However, little is known about the neural basis of implicit versus explicit learning. Here, we aimed to use anodal transcranial direct current stimulation (tDCS) to probe the relationship between different brain regions and learning mechanisms during a visuomotor adaptation task in humans. We hypothesized that anodal tDCS over the cerebellum (CB) should increase implicit learning while anodal tDCS over the dorsolateral prefrontal cortex (dlPFC), a region associated with higher-level cognition, should facilitate explicit learning. Using a horizontal visuomotor adaptation task that measures explicit/implicit contributions to learning (Taylor et al., 2014), we found that dlPFC stimulation significantly improved performance compared to the other groups, and weakly increased explicit learning. However, CB stimulation had no effects on either target error or implicit learning. Previous work showed variable CB stimulation effects only on a vertical visuomotor adaptation task (Jalali et al., 2017), so in Experiment 2, we conducted the same study using a vertical context to see if we could find effects of CB stimulation. We found only weak effects of CB stimulation on target error and implicit learning, and now the dlPFC effect did not replicate. To resolve this discrepancy, in Experiment 3, we examined the effect of context (vertical vs. horizontal) on implicit and explicit contributions and found that individuals performed significantly worse and used greater implicit learning in the vertical screen condition compared to the horizontal screen condition. Across all experiments, however, there was high inter-individual variability, with strong influences of a few individuals, suggesting that these effects are not consistent across individuals. Overall, this work provides preliminary support for the idea that different neural regions can be engaged to improve visuomotor adaptation, but shows that each region’s effects are highly context-dependent and not clearly dissociable from one another. This holds implications especially in neurorehabilitation, where an intact neural region could be engaged to potentially compensate if another region is impaired. Future work should examine factors influencing interindividual variability during these processes.
Keywords: Visuomotor adaptation-learning, tDCS, Explicit learning, implicit learning, Cerebellum, dorsolateral prefrontal cortex (DLPFC), Context-dependent learning

Liew, S.-L., Garrison, K. A., Ito, K. L., Heydari, P., Sobhani, M., Werner, J., Damasio, H., Winstein, C. J., & Aziz-Zadeh, L. (2018). Laterality of poststroke cortical motor activity during action observation is related to hemispheric dominance. Neural Plasticity, 2018, 3524960. Show abstractHide abstract

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.

Lopez-Alonso, V., Liew, S.-L., del Olmo, M. F., Cheeran, B., Sandrini, M., Abe, M., & Cohen, L. G. (2018). A preliminary comparison of motor learning across different non-invasive brain stimulation paradigms shows no consistent modulations. Frontiers in Neuroscience, 12, 253. Show abstractHide abstract

Non-invasive brain stimulation (NIBS) has been widely explored as a way to safely modulate brain activity and alter human performance for nearly three decades. Research using NIBS has grown exponentially within the last decade with promising results across a variety of clinical and healthy populations. However, recent work has shown high inter-individual variability and a lack of reproducibility of previous results. Here, we conducted a small preliminary study to explore the effects of three of the most commonly used excitatory NIBS paradigms over the primary motor cortex (M1) on motor learning (Sequential Visuomotor Isometric Pinch Force Tracking Task) and secondarily relate changes in motor learning to changes in cortical excitability (MEP amplitude and SICI). We compared anodal transcranial direct current stimulation (tDCS), paired associative stimulation (PAS25), and intermittent theta burst stimulation (iTBS), along with a sham tDCS control condition. Stimulation was applied prior to motor learning. Participants (n = 28) were randomized into one of the four groups and were trained on a skilled motor task. Motor learning was measured immediately after training (online), 1 day after training (consolidation), and 1 week after training (retention). We did not find consistent differential effects on motor learning or cortical excitability across groups. Within the boundaries of our small sample sizes, we then assessed effect sizes across the NIBS groups that could help power future studies. These results, which require replication with larger samples, are consistent with previous reports of small and variable effect sizes of these interventions on motor learning.


Journal Articles

Sprugnoli, G., Rossi, S., Emmendorfer, A., Rossi, A., Liew, S.-L., Tatti, E., di Lorenzo, G., Pascual-Leone, A., & Santarnecchi, E. (2017). Neural correlates of Eureka moment. Intelligence, 62, 99-118. Show abstractHide abstract

Insight processes that peak in “unpredictable moments of exceptional thinking” are often referred to as Aha! or Eureka moments. During insight, connections between previously unrelated concepts are made and new patterns arise at the perceptual level while new solutions to apparently insolvable problems suddenly emerge to consciousness. Given its unpredictable nature, the definition, and behavioral and neurophysiological measurement of insight problem solving represent a major challenge in contemporary cognitive neuroscience. Numerous attempts have been made, yet results show limited consistency across experimental approaches. Here we provide a comprehensive overview of available neuroscience of insight, including: i) a discussion about the theoretical definition of insight and an overview of the most widely accepted theoretical models, including those debating its relationship with creativity and intelligence; ii) an overview of available tasks used to investigate insight; iii) an ad-hoc quantitative meta-analysis of functional magnetic resonance imaging studies investigating the Eureka moment, using activation likelihood estimation maps; iv) a review of electroencephalographic evidence in the time and frequency domains, as well as v) an overview of the application of non-invasive brain stimulation techniques to causally assess the neurobiological basis of insight as well as enhance insight-related cognition.
Insight; Eureka; Aha; Cognition; fMRI; EEG; ERPs; Non-invasive brain stimulation; Neuroenhancement; NIBS; Creativity

Anglin, J. M., Sugiyama, T., & Liew, S.-L. (2017). Visuomotor adaptation in head-mounted virtual reality versus conventional training. Scientific Reports, 7, 45469. 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, 8, 29. 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.

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(1), 67-77. 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.

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), 1-7. 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.
Keywords: occupational therapy, occupational science, movement science, neural control of movement, neuroscience

Conference Presentations/Proceedings

Spicer, R., Anglin, J., Krum, D. M., & Liew, S.-L. (2017). REINVENT: A low-cost, virtual reality brain-computer interface for severe stroke upper limb motor recovery. In 2017 IEEE Virtual Reality (VR) (pp. 385-386). IEEE. Show abstractHide abstract

There are few effective treatments for rehabilitation of severe motor impairment after stroke. We developed a novel closed-loop neurofeedback system called REINVENT to promote motor recovery in this population. REINVENT (Rehabilitation Environment using the Integration of Neuromuscular-based Virtual Enhancements for Neural Training) harnesses recent advances in neuroscience, wearable sensors, and virtual technology and integrates low-cost electroencephalography (EEG) and electromyography (EMG) sensors with feedback in a head-mounted virtual reality display (VR) to provide neurofeedback when an individual's neuromuscular signals indicate movement attempt, even in the absence of actual movement. Here we describe the REINVENT prototype and provide evidence of the feasibility and safety of using REINVENT with older adults.

Anglin, J., Saldana, D., Schmiesing, A., & Liew, S.-L. (2017). Transfer of a skilled motor learning task between virtual and conventional environments. In 2017 IEEE Virtual Reality (VR) (pp. 401-402). IEEE. Show abstractHide abstract

Immersive, head-mounted virtual reality (HMD-VR) can be a potentially useful tool for motor rehabilitation. However, it is unclear whether the motor skills learned in HMD-VR transfer to the non-virtual world and vice-versa. Here we used a well-established test of skilled motor learning, the Sequential Visual Isometric Pinch Task (SVIPT), to train individuals in either an HMD-VR or conventional training (CT) environment. Participants were then tested in both environments. Our results show that participants who train in the CT environment have an improvement in motor performance when they transfer to the HMD-VR environment. In contrast, participants who train in the HMD-VR environment show a decrease in skill level when transferring to the CT environment. This has implications for how training in HMD-VR and CT may affect performance in different environments.


Journal Articles

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.-L., 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. 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.

Kan, E., Anglin, J., Borich, M., Jahanshad, N., Thompson, P., & Liew, S.-L. (2016). Facilitating big data meta-analyses for clinical neuroimaging through ENIGMA wrapper scripts. GigaScience, 5(Suppl. 1), 17-19. Show abstractHide abstract

A vast number of clinical disorders may involve changes in brain structure that are correlated with cognitive function and behavior (e.g., depression, schizophrenia, stroke, etc.). Reliably understanding the relationship between specific brain structures and relevant behaviors in worldwide clinical populations could dramatically improve healthcare decisions around the world. For instance, if a reliable relationship between brain structure after stroke and functional motor ability was established, brain imaging could be used to predict prognosis/recovery potential for individual patients. However, high heterogeneity in clinical populations in both individual neuroanatomy and behavioral outcomes make it difficult to develop accurate models of these potentially subtle relationships.
Large neuroimaging studies (n > 10,000) would provide unprecedented power to successfully relate clinical neuroanatomy changes with behavioral measures. While these sample sizes might be difficult for any one individual to collect, the ENIGMA Center for Worldwide-Medicine, Imaging, and Genomics has successfully pioneered meta-and mega-analytic methods to accomplish this task. ENIGMA [] brings together a global alliance of over 500 international researchers from over 35 countries to pool together neuroimaging data on different disease states in hopes of discovering critical brain-behavior relationships. Individual investigators with relevant data run ENIGMA analysis protocols on their own data and send back an output folder containing the analysis results to be combined with data from other sites for a meta-analysis. In this way, large sample sizes can be acquired without the hassle of large-scale data transfers or actual neuroimaging data sharing.
ENIGMA protocols were initially developed to harmonize processing methods of imaging researchers around the world and they require a moderate level of familiarity with several programming languages and environments. However, ENIGMA’s recent success has attracted greater interest in collaborative neuroimaging and protocols must be adjusted to allow for all levels of experience, as, the success of this approach depends on individual collaborators running these ENIGMA protocols on their data. Here, we worked on simplifying these protocols so even a novice programmer could use them. In this way, we hope to expand the feasibility of collecting critical clinical data from collaborators who may have less experience with neuroim-aging techniques.

Ito, K. L., & Liew, S.-L. (2016). Calculating the laterality index using FSL for stroke neuroimaging data. GigaScience, 5(Suppl. 1), 14-15. Show abstractHide abstract

The laterality index (LI) is one way to assess hemispheric dominance in a variety of tasks, such as language, cognitive functions, and changes in laterality in clinical populations, such as after stroke. In stroke neuroimaging, however, an optimal method of calculating the LI remains controversial, largely due to lesion variability in post-stroke brains.
Two main methods of calculating LI have evolved in neuroimaging literature. The first, more traditional approach counts the number of active voxels in a given region of interest (ROI) for each hemisphere. This method has been criticized for its inability to account for differences in signal intensity. Hence, a second approach calculates laterality based on the percent signal change within a given region; however, this method also has problems, such as difficulty handling negative values.
A laterality toolbox that addresses some of these issues has been implemented in the statistical neuroimaging analysis package SPM, which provides users with options of using either method, along with more advanced statistical tests for robust LI calculations [2] No such toolbox is yet available for FSL. Therefore, we developed a series of scripts to calculate LI in FSL using both voxel count and percent signal change methods. However, in the interest of space, here we present only results from the more robust method of the two (voxel count method).

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(7), 671-675. 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.

Buch, E. R., Liew, S.-L., & Cohen, L. G. (2016). Plasticity of sensorimotor networks: Multiple overlapping mechanisms. Neuroscientist, 23(2), 185-196. 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.

Conference Presentations/Proceedings

Anglin, J. M., Sugiyama, T., & Liew, S.-L. (2016, November). Visuomotor adaptation in head-mounted virtual reality versus conventional training. Presented at the Society for Neuroscience, San Diego, CA.

Liew, S.-L., Jahanshad, N., Anglin, J., Khoshab, N., Kim, B., Nakamura, W., Nhoung, H., Rondina, J., Tran, C., Borich, M., Boyd, L., Byblow, W., Dimyan, M., Ermer, E., Lang, C., Li, J., Nichols, T., Roberts, P., Sanossian, N., Soekadar, S., Stinear, C., Ward, N., Westlye, L. T., Winstein, C., Wittenberg, G. F., Cramer, S. C., & Thompson, P. M. (2016, November). ENIGMA Stroke Recovery: Big data neuroimaging to predict motor recovery. Presented at the Society for Neuroscience, San Diego, CA.

Liew, S.-L., Jahanshad, N., Anglin, J., Khoshab, N., Kim, B., Nakamura, W., Nhoung, H., Rondina, J., Tran, C., Borich, M., Boyd, L., Dimyan, M., Ermer, E., Lang, C., Li, J., Nichols, T., Roberts, P., Sanossian, N., Soekadar, S., Ward, N., Westlye, L. T., Winstein, C., Wittenberg, G. F., Cramer, S. C., & Thompson, P. M. (2016, June). ENIGMA Stroke Recovery: Big data neuroimaging to predict motor recovery. Presented at the Organization for Human Brain Mapping Annual Meeting, Geneva, Switzerland.


Journal Articles

Liew, S.-L., Santarnecchi, E., Buch, E. R., & Cohen, L. G. (2014). Non-invasive brain stimulation in neurorehabilitation: Local and distant effects for motor recovery. Frontiers in Human Neuroscience, 8, 378. 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.


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. 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.

Journal Articles

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. 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.

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. 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.

Garrison, K. A., Aziz-Zadeh, L., Wong, S. W., Liew, S.-L., & Winstein, C. J. (2013). Modulating the motor system by action observation after stroke. Stroke, 44(8), 2247-2253. Show abstractHide abstract

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.

Aziz-Zadeh, L. S., Liew, S.-L., & Dandekar, F. (2013). Exploring the neural correlates of visual creativity. Social Cognitive and Affective Neuroscience, 8(4), 475-480. 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. 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.


Journal Articles

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. 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(4), 811-819. 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.


Book Chapters

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.

Journal Articles

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. 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.

Johnson, A. J., Liew, S.-L., & Aziz-Zadeh, L. (2011). Demographics, learning and imitation, and body schema in Body Integrity Identity Disorder. Indiana University Undergraduate Journal of Cognitive Science, 6(2011), 8-15. Show abstractHide abstract

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

Liew, S.-L., Han, S., & Aziz-Zadeh, L. S. (2011). Familiarity modulates mirror neuron and mentalizing regions during intention understanding. Human Brain Mapping, 32(11), 1986-1997. 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.

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(2), 97-114. 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.