Ying-Hui Chou

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Chapters

• Chou, Y., Weingarten, C., Madden, D., Song, A., & Chen, N. (2012). Applications of virtual reality technology in brain imaging studies. In Virtual Reality.
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  Cumulative download = 2333 (12/21/2016)

Journals/Publications

• Chou, Y., Cowen, S., Sundman, M. H., Liu, Y., Lim, K., Ugonna, C., & Ton That, V. (2022). Association Between Responsiveness to Transcranial Magnetic Stimulation and Interhemispheric Functional Connectivity of Sensorimotor Cortex in Older Adults. Brain Connectivity. doi:10.1089/brain.2021.0180
• Chou, Y., Nadel, L., Chen, Y., Ton That, V., Ugonna, C., & Liu, Y. (2022). Diffusion MRI–guided theta burst stimulation enhances memory and functional connectivity along the inferior longitudinal fasciculus in mild cognitive impairment. Proceedings of the National Academy of Sciences, 119(21). doi:10.1073/pnas.2113778119
• Green, J. M., Sundman, M. H., & Chou, Y. H. (2022). Opioid-induced microglia reactivity modulates opioid reward, analgesia, and behavior. Neuroscience and biobehavioral reviews, 135, 104544.
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  Opioid-induced microglia reactivity affects opioid reward and analgesic processes in ways that may contribute to the neurocognitive impairment observed in opioid addicted individuals. Opioids elicit microglia reactivity through the actions of opioid metabolites at TLR4 receptors, that are located primarily on microglia but are also present on astrocytes. Specifically, the M3G metabolite, which has no affinity for opioid receptors, exerts off-target effects on TLR4 receptors that can trigger downstream immunologic consequences. This off-target microglial reactivity, and the subsequent increase in microglial release of TNFα, IL-1β, and BDNF, have been suggested to modulate both opioid-induced reward and opioid-induced analgesia. Despite occurring independently of each other, these neuro-immune effects could converge and result in overactivation of the insula. This would produce an imbalance between the "impulsive system" and the "executive system", such that the impulsive system's influence over behavior becomes dominant. This state, derived from changes in microglial reactivity, could contribute to impairment in a range of neurocognitive domains that are intricately involved in addiction and lead to increases in addiction-related behaviors.
• Zhou, W., Hsu, C., Chou, Y., Ashouri, Y., Murphy, D., & Trouard, T. (2022). Abstract TMP84: Baseline Cerebral Blood Flow Association With Cognitive Functions: Prospective Cohort Study.. Stroke, 53(Suppl_1). doi:10.1161/str.53.suppl_1.tmp84
• Grijalva, C., Toosizadeh, N., Sindorf, J., Chou, Y. H., & Laksari, K. (2021). Dual-task performance is associated with brain MRI Morphometry in individuals with mild cognitive impairment. Journal of neuroimaging : official journal of the American Society of Neuroimaging, 31(3), 588-601.
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  Cognitive impairment is a critical health problem in the elderly population. Research has shown that patients with mild cognitive impairment (MCI) may develop dementia in later years. Therefore, early identification of MCI could allow for interventions to help delay the progression of this devastating disease. Our objective in this study was to detect the early presence of MCI in elderly patients via neuroimaging and dual-task performance.
• Neill, M., Fisher, J. M., Brand, C., Lei, H., Sherman, S. J., Chou, Y. H., & Kuo, P. H. (2021). Practical Application of DaTQUANT with Optimal Threshold for Diagnostic Accuracy of Dopamine Transporter SPECT. Tomography (Ann Arbor, Mich.), 7(4), 980-989.
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  Evaluation of Parkinsonian Syndromes (PS) with Ioflupane iodine-123 dopamine transporter single photon emission computed tomography (DaT-SPECT), in conjunction with history and clinical examination, aids in diagnosis. FDA-approved, semi-quantitative software, DaTQUANT (GE Healthcare, Chicago, IL, USA) is available to assist in interpretation. This study aims to evaluate the optimal variables and thresholds of DaTQUANT to yield the optimal diagnostic accuracy. It is a retrospective review with three different patient populations. DaT-SPECT images from all three study groups were evaluated using DaTQUANT software, and both single and multi-variable logistic regression were used to model PS status. The optimal models were chosen via accuracy, sensitivity, and specificity, then evaluated on the other study groups. Among single variable models, the posterior putamen yielded the highest accuracy (84% to 95%), while balancing sensitivity and specificity. Multi-variable models did not substantially improve the accuracy. When the optimal single variable models for each group were used to evaluate the remaining two groups, comparable results were achieved. In typical utilization of DaT-SPECT for differentiation between nigrostriatal degenerative disease (NSDD) and non-NSDD, the posterior putamen was the single variable that yielded the highest accuracy across three different patient populations. The posterior putamen's recommended thresholds for DaTQUANT are SBR ≤ 1.0, z-score of ≤-1.8 and percent deviation ≤ -0.34.
• Chou, Y. H., Ton That, V., & Sundman, M. (2020). A systematic review and meta-analysis of rTMS effects on cognitive enhancement in mild cognitive impairment and Alzheimer's disease. Neurobiology of aging, 86, 1-10.
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  Repetitive transcranial magnetic stimulation (rTMS), a noninvasive brain stimulation technique, has emerged as a promising treatment for mild cognitive impairment (MCI) and Alzheimer's disease (AD). Currently, however, the effectiveness of this therapy is unclear because of the low statistical power and heterogeneity of previous trials. The purpose of the meta-analysis was to systematically characterize the effectiveness of various combinations of rTMS parameters on different cognitive domains in patients with MCI and AD. Thirteen studies comprising 293 patients with MCI or AD were included in this analysis. Random-effects analysis revealed an overall medium-to-large effect size (0.77) favoring active rTMS over sham rTMS in the improvement of cognitive functions. Subgroup analyses revealed that (1) high-frequency rTMS over the left dorsolateral prefrontal cortex and low-frequency rTMS at the right dorsolateral prefrontal cortex significantly improved memory functions; (2) high-frequency rTMS targeting the right inferior frontal gyrus significantly enhanced executive performance; and (3) the effects of 5-30 consecutive rTMS sessions could last for 4-12 weeks. Potential mechanisms of rTMS effects on cognitive functions are discussed.
• Chou, Y. H., Ton That, V., Chen, A. Y., Sundman, M., & Huang, Y. Z. (2020). TMS-induced seizure cases stratified by population, stimulation protocol, and stimulation site: A systematic literature search. Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology, 131(5), 1019-1020.
• Chou, Y., Rapcsak, S., Fellous, J., Wilson, R. C., Sundman, M. H., Lim, K., Ton That, V., Mizell, J., Ugonna, C., Rodriguez, R., Chen, N., Fuglevand, A. J., & Liu, Y. (2020). Transcranial magnetic stimulation reveals diminished homoeostatic metaplasticity in cognitively impaired adults. Brain Communications, 2(2). doi:10.1093/braincomms/fcaa203
• Kuo, P. H., Zhang, X., Stuehm, C., Chou, Y., & Chen, N. (2020). Functional Magnetic Resonance Imaging Reveals Taiji’s Real-time Effects on Neuronal Networks of the Brain. The Journal of Chinese Health Practices, 1(1).
• Sundman, M. H., Lim, K., Ton That, V., Mizell, J. M., Ugonna, C., Rodriguez, R., Chen, N. K., Fuglevand, A. J., Liu, Y., Wilson, R. C., Fellous, J. M., Rapcsak, S., & Chou, Y. H. (2020). Transcranial magnetic stimulation reveals diminished homoeostatic metaplasticity in cognitively impaired adults. Brain communications, 2(2), fcaa203.
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  Homoeostatic metaplasticity is a neuroprotective physiological feature that counterbalances Hebbian forms of plasticity to prevent network destabilization and hyperexcitability. Recent animal models highlight dysfunctional homoeostatic metaplasticity in the pathogenesis of Alzheimer's disease. However, the association between homoeostatic metaplasticity and cognitive status has not been systematically characterized in either demented or non-demented human populations, and the potential value of homoeostatic metaplasticity as an early biomarker of cognitive impairment has not been explored in humans. Here, we report that, through pre-conditioning the synaptic activity prior to non-invasive brain stimulation, the association between homoeostatic metaplasticity and cognitive status could be established in a population of non-demented human subjects (older adults across cognitive spectrums; all within the non-demented range). All participants ( = 40; age range, 65-74, 47.5% female) underwent a standardized neuropsychological battery, magnetic resonance imaging and a transcranial magnetic stimulation protocol. Specifically, we sampled motor-evoked potentials with an input/output curve immediately before and after repetitive transcranial magnetic stimulation to assess neural plasticity with two experimental paradigms: one with voluntary muscle contraction (i.e. modulated synaptic activity history) to deliberately introduce homoeostatic interference, and one without to serve as a control condition. From comparing neuroplastic responses across these experimental paradigms and across cohorts grouped by cognitive status, we found that (i) homoeostatic metaplasticity is diminished in our cohort of cognitively impaired older adults and (ii) this neuroprotective feature remains intact in cognitively normal participants. This novel finding suggests that (i) future studies should expand their scope beyond just Hebbian forms of plasticity that are traditionally assessed when using non-invasive brain stimulation to investigate cognitive ageing and (ii) the potential value of homoeostatic metaplasticity in serving as a biomarker for cognitive impairment should be further explored.
• Warren, S. M., Chou, Y. H., & Steklis, H. D. (2020). Potential for Resting-State fMRI of the Amygdala in Elucidating Neural Mechanisms of Adaptive Self-Regulatory Strategies: A Systematic Review. Brain connectivity, 10(1), 3-17.
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  Evolutionary-developmental theories consider the evolved mechanisms underlying adaptive behavioral strategies shaped in response to early environmental cues. Identifying neural mechanisms mediating processes of conditional adaptation in humans is an active area of research. Resting-state functional magnetic resonance imaging (RS-fMRI) captures functional connectivity theorized to represent the underlying functional architecture of the brain. This allows for investigating how underlying functional brain connections are related to early experiences during development, as well as current traits and behaviors. This review explores the potential of RS-fMRI of the amygdala (AMY) for advancing research on the neural mechanisms underlying adaptive strategies developed in early adverse environments. RS-fMRI studies of early life stress (ELS) and AMY functional connectivity within the frame of evolutionary theories are reviewed, specifically regarding the development of self-regulatory strategies. The potential of RS-fMRI for investigating the effects of ELS on developmental trajectories of self-regulation is discussed.
• Chen, N. K., Chou, Y. H., Sundman, M., Hickey, P., Kasoff, W. S., Bernstein, A., Trouard, T. P., Lin, T., Rapcsak, S. Z., Sherman, S. J., & Weingarten, C. P. (2018). Alteration of Diffusion-Tensor Magnetic Resonance Imaging Measures in Brain Regions Involved in Early Stages of Parkinson's Disease. Brain connectivity, 8(6), 343-349.
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  Many nonmotor symptoms (e.g., hyposmia) appear years before the cardinal motor features of Parkinson's disease (PD). It is thus desirable to be able to use noninvasive brain imaging methods, such as magnetic resonance imaging (MRI), to detect brain abnormalities in early PD stages. Among the MRI modalities, diffusion-tensor imaging (DTI) is suitable for detecting changes in brain tissue structure due to neurological diseases. The main purpose of this study was to investigate whether DTI signals measured from brain regions involved in early stages of PD differ from those of healthy controls. To answer this question, we analyzed whole-brain DTI data of 30 early-stage PD patients and 30 controls using improved region of interest-based analysis methods. Results showed that (i) the fractional anisotropy (FA) values in the olfactory tract (connected with the olfactory bulb: one of the first structures affected by PD) are lower in PD patients than healthy controls; (ii) FA values are higher in PD patients than healthy controls in the following brain regions: corticospinal tract, cingulum (near hippocampus), and superior longitudinal fasciculus (temporal part). Experimental results suggest that the tissue property, measured by FA, in olfactory regions is structurally modulated by PD with a mechanism that is different from other brain regions.
• Chou, Y. (2019). Yoga as advanced cognitive training: How Kirtan Kriya in Kundalini Yoga changes the PTSD brain.. Journal of Yoga and Physiotherapy, 7(4), 1-5.
• Seeley, S. H., Chou, Y. H., & O'Connor, M. F. (2018). Intranasal oxytocin and OXTR genotype effects on resting state functional connectivity: A systematic review. Neuroscience and biobehavioral reviews, 95, 17-32.
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  Evaluate effects of intranasal oxytocin (IN-OT) and OXTR genotype on resting state functional connectivity in the human brain.
• Chou, Y., Sundman, M., Whitson, H. E., Gaur, P., Chu, M., Weingarten, C. P., Madden, D. J., Wang, L., Kirste, I., Joliot, M., Diaz, M. T., Li, Y., Song, A. W., & Chen, N. (2017). Maintenance and Representation of Mind Wandering during Resting-State fMRI. Scientific reports, 7, 40722.
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  Major advances in resting-state functional magnetic resonance imaging (fMRI) techniques in the last two decades have provided a tool to better understand the functional organization of the brain both in health and illness. Despite such developments, characterizing regulation and cerebral representation of mind wandering, which occurs unavoidably during resting-state fMRI scans and may induce variability of the acquired data, remains a work in progress. Here, we demonstrate that a decrease or decoupling in functional connectivity involving the caudate nucleus, insula, medial prefrontal cortex and other domain-specific regions was associated with more sustained mind wandering in particular thought domains during resting-state fMRI. Importantly, our findings suggest that temporal and between-subject variations in functional connectivity of above-mentioned regions might be linked with the continuity of mind wandering. Our study not only provides a preliminary framework for characterizing the maintenance and cerebral representation of different types of mind wandering, but also highlights the importance of taking mind wandering into consideration when studying brain organization with resting-state fMRI in the future.
• Madden, D. J., Parks, E. L., Tallman, C. W., Boylan, M. A., Hoagey, D. A., Cocjin, S. B., Johnson, M. A., Chou, Y., Potter, G. G., Chen, N., Packard, L. E., Siciliano, R. E., Monge, Z. A., & Diaz, M. T. (2017). Frontoparietal activation during visual conjunction search: Effects of bottom-up guidance and adult age. Human brain mapping.
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  We conducted functional magnetic resonance imaging (fMRI) with a visual search paradigm to test the hypothesis that aging is associated with increased frontoparietal involvement in both target detection and bottom-up attentional guidance (featural salience). Participants were 68 healthy adults, distributed continuously across 19 to 78 years of age. Frontoparietal regions of interest (ROIs) were defined from resting-state scans obtained prior to task-related fMRI. The search target was defined by a conjunction of color and orientation. Each display contained one item that was larger than the others (i.e., a size singleton) but was not informative regarding target identity. Analyses of search reaction time (RT) indicated that bottom-up attentional guidance from the size singleton (when coincident with the target) was relatively constant as a function of age. Frontoparietal fMRI activation related to target detection was constant as a function of age, as was the reduction in activation associated with salient targets. However, for individuals 35 years of age and older, engagement of the left frontal eye field (FEF) in bottom-up guidance was more prominent than for younger individuals. Further, the age-related differences in left FEF activation were a consequence of decreasing resting-state functional connectivity in visual sensory regions. These findings indicate that age-related compensatory effects may be expressed in the relation between activation and behavior, rather than in the magnitude of activation, and that relevant changes in the activation-RT relation may begin at a relatively early point in adulthood. Hum Brain Mapp, 2017. © 2017 Wiley Periodicals, Inc.
• Madden, D. J., Parks, E. L., Tallman, C. W., Boylan, M. A., Hoagey, D. A., Cocjin, S. B., Packard, L. E., Johnson, M. A., Chou, Y. H., Potter, G. G., Chen, N. K., Siciliano, R. E., Monge, Z. A., Honig, J. A., & Diaz, M. T. (2017). Sources of disconnection in neurocognitive aging: cerebral white-matter integrity, resting-state functional connectivity, and white-matter hyperintensity volume. Neurobiology of aging, 54, 199-213.
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  Age-related decline in fluid cognition can be characterized as a disconnection among specific brain structures, leading to a decline in functional efficiency. The potential sources of disconnection, however, are unclear. We investigated imaging measures of cerebral white-matter integrity, resting-state functional connectivity, and white-matter hyperintensity volume as mediators of the relation between age and fluid cognition, in 145 healthy, community-dwelling adults 19-79 years of age. At a general level of analysis, with a single composite measure of fluid cognition and single measures of each of the 3 imaging modalities, age exhibited an independent influence on the cognitive and imaging measures, and the imaging variables did not mediate the age-cognition relation. At a more specific level of analysis, resting-state functional connectivity of sensorimotor networks was a significant mediator of the age-related decline in executive function. These findings suggest that different levels of analysis lead to different models of neurocognitive disconnection, and that resting-state functional connectivity, in particular, may contribute to age-related decline in executive function.
• Sundman, M. H., Chen, N. K., Subbian, V., & Chou, Y. H. (2017). The bidirectional gut-brain-microbiota axis as a potential nexus between traumatic brain injury, inflammation, and disease. Brain, behavior, and immunity, 66, 31-44.
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  As head injuries and their sequelae have become an increasingly salient matter of public health, experts in the field have made great progress elucidating the biological processes occurring within the brain at the moment of injury and throughout the recovery thereafter. Given the extraordinary rate at which our collective knowledge of neurotrauma has grown, new insights may be revealed by examining the existing literature across disciplines with a new perspective. This article will aim to expand the scope of this rapidly evolving field of research beyond the confines of the central nervous system (CNS). Specifically, we will examine the extent to which the bidirectional influence of the gut-brain axis modulates the complex biological processes occurring at the time of traumatic brain injury (TBI) and over the days, months, and years that follow. In addition to local enteric signals originating in the gut, it is well accepted that gastrointestinal (GI) physiology is highly regulated by innervation from the CNS. Conversely, emerging data suggests that the function and health of the CNS is modulated by the interaction between 1) neurotransmitters, immune signaling, hormones, and neuropeptides produced in the gut, 2) the composition of the gut microbiota, and 3) integrity of the intestinal wall serving as a barrier to the external environment. Specific to TBI, existing pre-clinical data indicates that head injuries can cause structural and functional damage to the GI tract, but research directly investigating the neuronal consequences of this intestinal damage is lacking. Despite this void, the proposed mechanisms emanating from a damaged gut are closely implicated in the inflammatory processes known to promote neuropathology in the brain following TBI, which suggests the gut-brain axis may be a therapeutic target to reduce the risk of Chronic Traumatic Encephalopathy and other neurodegenerative diseases following TBI. To better appreciate how various peripheral influences are implicated in the health of the CNS following TBI, this paper will also review the secondary biological injury mechanisms and the dynamic pathophysiological response to neurotrauma. Together, this review article will attempt to connect the dots to reveal novel insights into the bidirectional influence of the gut-brain axis and propose a conceptual model relevant to the recovery from TBI and subsequent risk for future neurological conditions.
• McClernon, F. J., Conklin, C. A., Kozink, R. V., Adcock, R. A., Sweitzer, M. M., Addicott, M. A., Chou, Y., Chen, N., Hallyburton, M. B., & DeVito, A. M. (2016). Hippocampal and Insular Response to Smoking-Related Environments: Neuroimaging Evidence for Drug-Context Effects in Nicotine Dependence. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 41(3), 877-85.
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  Environments associated with prior drug use provoke craving and drug taking, and set the stage for lapse/relapse. Although the neurobehavioral bases of environment-induced drug taking have been investigated with animal models, the influence of drug-environments on brain function and behavior in clinical populations of substance users is largely unexplored. Adult smokers (n=40) photographed locations personally associated with smoking (personal smoking environments; PSEs) or personal nonsmoking environment (PNEs). Following 24-h abstinence, participants underwent fMRI scanning while viewing PSEs, PNEs, standard smoking and nonsmoking environments, as well as proximal smoking (eg, lit cigarette) and nonsmoking (eg, pencil) cues. Finally, in two separate sessions following 6-h abstinence they viewed either PSEs or PNEs while cue-induced self-reported craving and smoking behavior were assessed. Viewing PSEs increased blood oxygen level-dependent signal in right posterior hippocampus (pHPC; F(2,685)=3.74, p
• Chou, Y., Hickey, P. T., Sundman, M., Song, A. W., & Chen, N. (2015). Effects of repetitive transcranial magnetic stimulation on motor symptoms in Parkinson disease: a systematic review and meta-analysis. JAMA neurology, 72(4), 432-40.
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  Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive neuromodulation technique that has been closely examined as a possible treatment for Parkinson disease (PD). However, results evaluating the effectiveness of rTMS in PD are mixed, mostly owing to low statistical power or variety in individual rTMS protocols.
• Chou, Y., You, H., Wang, H., Zhao, Y., Hou, B., Chen, N., & Feng, F. (2015). Effect of Repetitive Transcranial Magnetic Stimulation on fMRI Resting-State Connectivity in Multiple System Atrophy. Brain connectivity, 5(7), 451-9.
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  Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive neuromodulation technique that has been used to treat neurological and psychiatric conditions. Although results of rTMS intervention are promising, so far, little is known about the rTMS effect on brain functional networks in clinical populations. In this study, we used a whole-brain connectivity analysis of resting-state functional magnetic resonance imaging data to uncover changes in functional connectivity following rTMS intervention and their association with motor symptoms in patients with multiple system atrophy (MSA). Patients were randomized to active rTMS or sham rTMS groups and completed a 10-session 5-Hz rTMS treatment over the left primary motor area. The results showed significant rTMS-related changes in motor symptoms and functional connectivity. Specifically, (1) significant improvement of motor symptoms was observed in the active rTMS group, but not in the sham rTMS group; and (2) several functional links involving the default mode, cerebellar, and limbic networks exhibited positive changes in functional connectivity in the active rTMS group. Moreover, the positive changes in functional connectivity were associated with improvement in motor symptoms for the active rTMS group. The present findings suggest that rTMS may improve motor symptoms by modulating functional links connecting to the default mode, cerebellar, and limbic networks, inferring a future therapeutic candidate for patients with MSA.
• Li, W., Langkammer, C., Chou, Y., Petrovic, K., Schmidt, R., Song, A. W., Madden, D. J., Ropele, S., & Liu, C. (2015). Association between increased magnetic susceptibility of deep gray matter nuclei and decreased motor function in healthy adults. NeuroImage, 105, 45-52.
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  In the human brain, iron is more prevalent in gray matter than in white matter, and deep gray matter structures, particularly the globus pallidus, putamen, caudate nucleus, substantia nigra, red nucleus, and dentate nucleus, exhibit especially high iron content. Abnormally elevated iron levels have been found in various neurodegenerative diseases. Additionally, iron overload and related neurodegeneration may also occur during aging, but the functional consequences are not clear. In this study, we explored the correlation between magnetic susceptibility--a surrogate marker of brain iron--of these gray matter structures with behavioral measures of motor and cognitive abilities, in 132 healthy adults aged 40-83 years. Latent variables corresponding to manual dexterity and executive functions were obtained using factor analysis. The factor scores for manual dexterity declined significantly with increasing age. Independent of gender, age, and global cognitive function, increasing magnetic susceptibility in the globus pallidus and red nuclei was associated with decreasing manual dexterity. This finding suggests the potential value of magnetic susceptibility, a non-invasive quantitative imaging marker of iron, for the study of iron-related brain function changes.
• Wang, L., Chou, Y., Potter, G. G., & Steffens, D. C. (2015). Altered Synchronizations among Neural Networks in Geriatric Depression. BioMed research international, 2015, 343720.
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  Although major depression has been considered as a manifestation of discoordinated activity between affective and cognitive neural networks, only a few studies have examined the relationships among neural networks directly. Because of the known disconnection theory, geriatric depression could be a useful model in studying the interactions among different networks. In the present study, using independent component analysis to identify intrinsically connected neural networks, we investigated the alterations in synchronizations among neural networks in geriatric depression to better understand the underlying neural mechanisms. Resting-state fMRI data was collected from thirty-two patients with geriatric depression and thirty-two age-matched never-depressed controls. We compared the resting-state activities between the two groups in the default-mode, central executive, attention, salience, and affective networks as well as correlations among these networks. The depression group showed stronger activity than the controls in an affective network, specifically within the orbitofrontal region. However, unlike the never-depressed controls, geriatric depression group lacked synchronized/antisynchronized activity between the affective network and the other networks. Those depressed patients with lower executive function has greater synchronization between the salience network with the executive and affective networks. Our results demonstrate the effectiveness of the between-network analyses in examining neural models for geriatric depression.
• Whitson, H. E., Chou, Y., Potter, G. G., Diaz, M. T., Chen, N., Lad, E. M., Johnson, M. A., Cousins, S. W., Zhuang, J., & Madden, D. J. (2015). Phonemic fluency and brain connectivity in age-related macular degeneration: a pilot study. Brain connectivity, 5(2), 126-35.
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  Age-related macular degeneration (AMD), the leading cause of blindness in developed nations, has been associated with poor performance on tests of phonemic fluency. This pilot study sought to (1) characterize the relationship between phonemic fluency and resting-state functional brain connectivity in AMD patients and (2) determine whether regional connections associated with phonemic fluency in AMD patients were similarly linked to phonemic fluency in healthy participants. Behavior-based connectivity analysis was applied to resting-state, functional magnetic resonance imaging data from seven patients (mean age=79.9±7.5 years) with bilateral AMD who completed fluency tasks prior to imaging. Phonemic fluency was inversely related to the strength of functional connectivity (FC) among six pairs of brain regions, representing eight nodes: left opercular portion of inferior frontal gyrus (which includes Broca's area), left superior temporal gyrus (which includes part of Wernicke's area), inferior parietal lobe (bilaterally), right superior parietal lobe, right supramarginal gyrus, right supplementary motor area, and right precentral gyrus. The FC of these reference links was not related to phonemic fluency among 32 healthy individuals (16 younger adults, mean age=23.5±4.6 years and 16 older adults, mean age=68.3±3.4 years). Compared with healthy individuals, AMD patients exhibited higher mean connectivity within the reference links and within the default mode network, possibly reflecting compensatory changes to support performance in the setting of reduced vision. These findings are consistent with the hypothesis that phonemic fluency deficits in AMD reflect underlying brain changes that develop in the context of AMD.
• Chang, H., Gaur, P., Chou, Y., Chu, M., & Chen, N. (2014). Interleaved EPI based fMRI improved by multiplexed sensitivity encoding (MUSE) and simultaneous multi-band imaging. PloS one, 9(12), e116378.
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  Functional magnetic resonance imaging (fMRI) is a non-invasive and powerful imaging tool for detecting brain activities. The majority of fMRI studies are performed with single-shot echo-planar imaging (EPI) due to its high temporal resolution. Recent studies have demonstrated that, by increasing the spatial-resolution of fMRI, previously unidentified neuronal networks can be measured. However, it is challenging to improve the spatial resolution of conventional single-shot EPI based fMRI. Although multi-shot interleaved EPI is superior to single-shot EPI in terms of the improved spatial-resolution, reduced geometric distortions, and sharper point spread function (PSF), interleaved EPI based fMRI has two main limitations: 1) the imaging throughput is lower in interleaved EPI; 2) the magnitude and phase signal variations among EPI segments (due to physiological noise, subject motion, and B0 drift) are translated to significant in-plane aliasing artifact across the field of view (FOV). Here we report a method that integrates multiple approaches to address the technical limitations of interleaved EPI-based fMRI. Firstly, the multiplexed sensitivity-encoding (MUSE) post-processing algorithm is used to suppress in-plane aliasing artifacts resulting from time-domain signal instabilities during dynamic scans. Secondly, a simultaneous multi-band interleaved EPI pulse sequence, with a controlled aliasing scheme incorporated, is implemented to increase the imaging throughput. Thirdly, the MUSE algorithm is then generalized to accommodate fMRI data obtained with our multi-band interleaved EPI pulse sequence, suppressing both in-plane and through-plane aliasing artifacts. The blood-oxygenation-level-dependent (BOLD) signal detectability and the scan throughput can be significantly improved for interleaved EPI-based fMRI. Our human fMRI data obtained from 3 Tesla systems demonstrate the effectiveness of the developed methods. It is expected that future fMRI studies requiring high spatial-resolvability and fidelity will largely benefit from the reported techniques.
• Madden, D. J., Parks, E. L., Davis, S. W., Diaz, M. T., Potter, G. G., Chou, Y., Chen, N., & Cabeza, R. (2014). Age mediation of frontoparietal activation during visual feature search. NeuroImage, 102 Pt 2, 262-74.
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  Activation of frontal and parietal brain regions is associated with attentional control during visual search. We used fMRI to characterize age-related differences in frontoparietal activation in a highly efficient feature search task, detection of a shape singleton. On half of the trials, a salient distractor (a color singleton) was present in the display. The hypothesis was that frontoparietal activation mediated the relation between age and attentional capture by the salient distractor. Participants were healthy, community-dwelling individuals, 21 younger adults (19-29 years of age) and 21 older adults (60-87 years of age). Top-down attention, in the form of target predictability, was associated with an improvement in search performance that was comparable for younger and older adults. The increase in search reaction time (RT) associated with the salient distractor (attentional capture), standardized to correct for generalized age-related slowing, was greater for older adults than for younger adults. On trials with a color singleton distractor, search RT increased as a function of increasing activation in frontal regions, for both age groups combined, suggesting increased task difficulty. Mediational analyses disconfirmed the hypothesized model, in which frontal activation mediated the age-related increase in attentional capture, but supported an alternative model in which age was a mediator of the relation between frontal activation and capture.
• Song, X., Panych, L. P., Chou, Y., & Chen, N. (2014). A Study of Long-Term fMRI Reproducibility Using Data-Driven Analysis Methods. International journal of imaging systems and technology, 24(4), 339-349.
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  The reproducibility of functional magnetic resonance imaging (fMRI) is important for fMRI-based neuroscience research and clinical applications. Previous studies show considerable variation in amplitude and spatial extent of fMRI activation across repeated sessions on individual subjects even using identical experimental paradigms and imaging conditions. Most existing fMRI reproducibility studies were typically limited by time duration and data analysis techniques. Particularly, the assessment of reproducibility is complicated by a fact that fMRI results may depend on data analysis techniques used in reproducibility studies. In this work, the long-term fMRI reproducibility was investigated with a focus on the data analysis methods. Two spatial smoothing techniques, including a wavelet-domain Bayesian method and the Gaussian smoothing, were evaluated in terms of their effects on the long-term reproducibility. A multivariate support vector machine (SVM)-based method was used to identify active voxels, and compared to a widely used general linear model (GLM)-based method at the group level. The reproducibility study was performed using multisession fMRI data acquired from eight healthy adults over 1.5 years' period of time. Three regions-of-interest (ROI) related to a motor task were defined based upon which the long-term reproducibility were examined. Experimental results indicate that different spatial smoothing techniques may lead to different reproducibility measures, and the wavelet-based spatial smoothing and SVM-based activation detection is a good combination for reproducibility studies. On the basis of the ROIs and multiple numerical criteria, we observed a moderate to substantial within-subject long-term reproducibility. A reasonable long-term reproducibility was also observed from the inter-subject study. It was found that the short-term reproducibility is usually higher than the long-term reproducibility. Furthermore, the results indicate that brain regions with high contrast-to-noise ratio do not necessarily exhibit high reproducibility. These findings may provide supportive information for optimal design/implementation of fMRI studies and data interpretation.
• Chou, Y., Chen, N., & Madden, D. J. (2013). Functional brain connectivity and cognition: effects of adult age and task demands. Neurobiology of aging, 34(8), 1925-34.
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  Previous neuroimaging research has documented that patterns of intrinsic (resting state) functional connectivity (FC) among brain regions covary with individual measures of cognitive performance. Here, we examined the relation between intrinsic FC and a reaction time (RT) measure of performance, as a function of age group and task demands. We obtained filtered, event-related functional magnetic resonance imaging data, and RT measures of visual search performance, from 21 younger adults (19-29 years old) and 21 healthy, older adults (60-87 years old). Age-related decline occurred in the connectivity strength in multiple brain regions, consistent with previous findings. Among 8 pairs of regions, across somatomotor, orbitofrontal, and subcortical networks, increasing FC was associated with faster responding (lower RT). Relative to younger adults, older adults exhibited a lower strength of this RT-connectivity relation and greater disruption of this relation by a salient but irrelevant display item (color singleton distractor). Age-related differences in the covariation of intrinsic FC and cognitive performance vary as a function of task demands.
• Chou, Y. H., Panych, L. P., Dickey, C. C., Petrella, J. R., & Chen, N. K. (2012). Investigation of long-term reproducibility of intrinsic connectivity network mapping: a resting-state fMRI study. AJNR. American journal of neuroradiology, 33(5), 833-8.
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  Connectivity mapping based on resting-state fMRI is rapidly developing, and this methodology has great potential for clinical applications. However, before resting-state fMRI can be applied for diagnosis, prognosis, and monitoring treatment for an individual patient with neurologic or psychiatric diseases, it is essential to assess its long-term reproducibility and between-subject variations among healthy individuals. The purpose of the study was to quantify the long-term test-retest reproducibility of ICN measures derived from resting-state fMRI and to assess the between-subject variation of ICN measures across the whole brain.
• Young, D. E., Wagenaar, R. C., Lin, C., Chou, Y., Davidsdottir, S., Saltzman, E., & Cronin-Golomb, A. (2010). Visuospatial perception and navigation in Parkinson's disease. Vision research, 50(23), 2495-504.
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  A shifted field of view, an altered perception of optic flow speed, and gait asymmetries may influence heading direction in Parkinson's disease (PD). PD participants (left body-side onset, LPD, n=14; right body-side onset, RPD, n=9) and Healthy Control participants (n=17) walked a virtual hallway in which the optic flow speeds of the walls varied. Three-dimensional kinematics showed participants veered away from the faster moving wall. Although veering normally occurs toward the side with smaller step length, in both LPD and RPD this bias was overridden by a shifted field of view, which caused veering in the opposite direction, toward the side of the brain with more basal ganglia damage.
• Chen, N., Chou, Y., Song, A. W., & Madden, D. J. (2009). Measurement of spontaneous signal fluctuations in fMRI: adult age differences in intrinsic functional connectivity. Brain structure & function, 213(6), 571-85.
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  Functional connectivity (FC) reflects the coherence of spontaneous, low-frequency fluctuations in functional magnetic resonance imaging (fMRI) data. We report a behavior-based connectivity analysis method, in which whole-brain data are used to identify behaviorally relevant, intrinsic FC networks. Nineteen younger adults (20-28 years) and 19 healthy, older adults (63-78 years) were assessed with fMRI and diffusion tensor imaging (DTI). Results indicated that FC involving a distributed network of brain regions, particularly the inferior frontal gyri, exhibited age-related change in the correlation with perceptual-motor speed (choice reaction time; RT). No relation between FC and RT was evident for younger adults, whereas older adults exhibited a significant age-related slowing of perceptual-motor speed, which was mediated by decreasing FC. Older adults' FC values were in turn associated positively with white matter integrity (from DTI) within the genu of the corpus callosum. The developed FC analysis illustrates the value of identifying connectivity by combining structural, functional, and behavioral data.
• Chou, Y., Wagenaar, R. C., Saltzman, E., Giphart, J. E., Young, D., Davidsdottir, R., & Cronin-Golomb, A. (2009). Effects of optic flow speed and lateral flow asymmetry on locomotion in younger and older adults: a virtual reality study. The journals of gerontology. Series B, Psychological sciences and social sciences, 64(2), 222-31.
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  The purpose of the study is to investigate whether there are age-related differences in locomotion due to changes in presence of vision, optic flow speed, and lateral flow asymmetry using virtual reality technology. Gait kinematics and heading direction were measured using a three-dimensional motion analysis system. Although older and younger adults were affected differentially by the availability of vision, a greater dependence on optic flow information in older adults during walking was not found. Linear relations were observed between walking performance and flow speed as well as heading direction and flow asymmetry. The findings suggest that the ability to integrate optic flow information into the multimodal system for assessment of walking speed and heading direction is comparable in older and younger adults.
• Yeh, L., Gau, M., Chou, Y., Tseng, M., Lee, S., & Chi, H. (2009). Attitudes and knowledge on breastfeeding among occupational therapists. Journal of Taiwan Occupational Therapy Research and Practice, 5, 116-127.
• Chou, Y., Coster, W. J., Latham, C. A., Li, P., Chung, M., & Shie, J. (2008). Voluntary manual exploration and vision in rod bisection. Perceptual and motor skills, 107(1), 70-80.
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  Two experiments were carried out to investigate contributions of voluntary manual exploration and vision to rod-bisection performance when the rod was placed in different spatial positions. Analysis showed both voluntary manual exploration and vision contributed to the accuracy of rod-bisection performance in healthy adults (Exp. 1: 12 men, 13 women; Exp. 2: 10 men, 11 women). Advantages of voluntary manual exploration were related to rod position and initial search direction. Results are discussed with regard to ecological approach to action and perception, two cortical systems (ventral and dorsal streams) for perception and control of actions, and the hemispheric activation hypothesis.
• Giphart, J. E., Chou, Y., Kim, D. H., Bortnyk, C. T., & Wagenaar, R. C. (2007). Effects of virtual reality immersion and walking speed on coordination of arm and leg movements. PRESENCE-TELEOPERATORS AND VIRTUAL ENVIRONMENTS, 16(4), 399-413.
• Chou, Y., & Lin, K. (1998). The quick neurological screening test: Psychometric considerations. Journal of Occupational Therapy Association, R.O.C., 16, 37-51.

Proceedings Publications

• Weinkauf, C. C., Trouard, T. P., Chou, Y., Chen, N., Guzman Perez-Carrillo, G., Ryan, T. L., Altbach, M. I., Johnson, K., Bruck, D., Ugonna, C., McKinnon, A., Bernstein, A. S., & Lindley, M. (2019, Spring). Functional and Microstructural Changes in the Brain After Carotid Endarterectomy. In International Society for Magnetic Resonance in Medicine.
• Lindley, M., Bernstein, A., Ugonna, C., Bruck, D., Johnson, K., Altbach, M. I., Ryan, L., Chen, N., Chou, Y., Guzman Perez-Carrillo, G., Trouard, T. P., & Weinkauf, C. C. (2018, June). Impact of Carotid Endarterectomy on Functional Connectivity. In Joint International Society for Magnetic Resonance in Medicine & The European Society for Magnetic Resonance in Medicine and Biology (ISMRM-ESMRMB) Annual Meeting, 5562.

Presentations

• Chou, Y. (2021, February). Panelist. BIO5 Inspiring Women in STEM. Tucson: BIO5, University of Arizona.
• Chou, Y. (2020, May). TMS to Enhance Cognitive Function in Cancer Patients. Cancer Imaging Program Meeting. Tucson: Cancer Center, University of Arizona.
• Chou, Y. (2019, March). Transcranial magnetic stimulation for Parkinson’s disease. Science Cafe. Tucson: College of Science, U of A.
• Chou, Y. (2019, November). Integrating MRI with Transcranial Magnetic Stimulation. Arizona Research Institute for Biomedical Imaging (ARIBI) workshop. Tucson: Arizona Research Institute for Biomedical Imaging.
• Chou, Y. (2019, November). Transcranial Magnetic Stimulation for Alzheimer’s Disease and Mild Cognitive Impairment.. Neuroscience GIDP Colloquium. Tucson: Neuroscience GIDP, U of A.
• Chou, Y. (2018, April). Transcranial Magnetic Stimulation for Mild Cognitive Impairment. TMS Workshop. Tucson: BIO5, U of A.
• Chou, Y. (2018, August). Transcranial Magnetic Stimulation for Parkinson’s Disease. Parkinson Wellness Recovery – 2018 Wellness Series at PWR!Gym. Tucson: PWR!Gym.
• Chou, Y. (2018, February). Development of Image-Guided Transcranial Magnetic Stimulation Protocols for Memory Therapeutics. McKnight Brain Institute Site Visit. Tucson: McKnight Brain Institute.
• Chou, Y. (2018, March). Transcranial Magnetic Stimulation and Mild Cognitive Impairment. Arizona Alzheimer’s Consortium Retreat. Sedona, AZ: Arizona Alzheimer’s Consortium.
• Chou, Y. (2018, May). Cortical Excitability in Alzheimer’s Disease and Mild Cognitive Impairment: A Systematic Review and Meta-Analysis. Arizona Alzheimer’s Consortium Scientific Conference. Phoenix: Arizona Alzheimer’s Consortium.
• Chou, Y. (2018, May). Introduction to Transcranial Magnetic Stimulation. Cancer Imaging Retreat. Tucson: Cancer Center, U of A.
• Chou, Y. (2018, November). Transcranial magnetic stimulation for Parkinson’s disease. Parkinson’s Datablitz. Tucson: University of Arizona.
• Chou, Y. (2018, October). Hippocampal functional connectivity in healthy older adults. Arizona Alzheimer’s Consortium PI Meeting. Tucson: Arizona Alzheimer’s Consortium.
• Chou, Y. (2017, April). Repetitive Transcranial Magnetic Stimulation and Functional Connectivity Mapping in Clinical and Psychological Research. Cognitive Science Colloquium.
• Chou, Y. (2017, March). Integrating TMS with Brain Imaging: Applications for Parkinson’s Disease. Psychology Colloquium.
• Chou, Y. (2017, May). Integrating transcranial magnetic stimulation with brain Imaging: Applications for clinical populations. Arizona Research Institute for Biomedical Imaging (ARIBI) Workshop.
• Chou, Y. (2017, May). Introduction to Transcranial Magnetic Stimulation (TMS): Applications for Parkinson’s Disease. Tucson Parkinson Disease Conference. Tucson: Parkinson & Movement Disorder Alliance.
• Chou, Y. (2016, December). Integration of TMS and MRI: Clinical Applications. Biomedical Engineering and MRI Group.
• Chou, Y. (2016, December). Introduction to Transcranial Magnetic Stimulation. Brain Mapping Workshop.
• Chou, Y. (2016, November). Integration of TMS and MRI: Clinical and Neuropsychological Applications. CNS Seminar.

Poster Presentations

• Chou, Y. (2021, February). Women and chemobrain: An investigation into the relationship between chemotherapy, estrogen, and menopause. UBRP Conference. Tucson: University of Arizona.
• Chou, Y. (2020, January). Effect of excitatory and inhibitory theta burst stimulation (TBS) on resting state connectivity. 20th Annual Virtual Meeting of the Society for the Neurobiology of Language. Virtual: Society for the Neurobiology of Language.
• Chou, Y. (2020, March). Cortical excitability in Alzheimer’s disease and mild cognitive impairment: A systematic review and meta-analysis of transcranial magnetic stimulation studies. CNS 2020 Virtual Meeting. Virtual: Cognitive Neuroscience Society.
• Chou, Y. (2019, April). Divergent effects on cortical excitability observed in healthy older adults during active voluntary contraction following motor cortex iTBS. 3rd International Brain Stimulation Conference. Vancouver, Canada: Elsevier.
• Chou, Y. (2019, April). Effects of repetitive transcranial magnetic stimulation on cognitive function in Alzheimer’s disease and mild cognitive impairment: A systematic review and meta-analysis. 3rd International Brain Stimulation Conference. Vancouver, Canada: Elsevier.
• Chou, Y. (2019, April). Hippocampal functional connectivity in healthy older adults. The Third Biennial Conference on Resting-State and Brain Connectivity. Montreal, Canada: Brain Connectivity Journal.
• Chou, Y. (2019, June). Differential Effects of Cardiovascular Risk Factors on Cognitive Function in Patients with Severe Carotid Stenosis. Vascular Annual Meeting. National Harbor, MD.: Society for Vascular Surgery.
• Chou, Y. (2019, May). Functional impact of theta burst stimulation on motor cortex. 27th ISMRM Annual Meeting & Exhibition. Montreal, Canada: International Society of Magnetic Resonance in Medicine.
• Chou, Y. (2018, July). Effects of repetitive transcranial magnetic stimulation on cognitive Function in mild cognitive impairment: A systematic review and meta-analysis. Alzheimer’s Association International Conference. Chicago, IL: Alzheimer’s Association.
• Chou, Y. (2018, May). Cortical excitability in Alzheimer’s disease and mild cognitive impairment: A systematic review and meta-analysis. Arizona Alzheimer’s Consortium Annual Scientific Conference. Phoenix, AZ: Arizona Alzheimer’s Consortium.
• Chou, Y. (2018, May). Modulation of perfusion and functional connectivity by intermittent theta burst stimulation. The Joint Annual Meeting ISMRM-ESMRMB. Paris, France: International Society of Magnetic Resonance Imaging in Medicine.
• Chou, Y. (2018, May). fMRI and upper-extremity function: The effect of dual-tasking. Cognitive Aging Conference. Atlanta, GA.
• Chou, Y. (2017, June). Sources of disconnection in neurocognitive aging. Annual Meeting of Human Brain Mapping. Vancouver, Canada: Human Brain Mapping.
• Chou, Y. (2017, September). Non-motor symptoms as a marker of Parkinson’s Disease progression: An exploratory analysis. Biomedical Engineering Society Annual Meeting. Phoenix, AZ: Biomedical Engineering Society.
• Tirambulo, C., Sutherland-Mills, C., Toosizadeh, N., Lindley, M., Golden, T., Chen, N., Mohler, J., & Chou, Y. (2017, November). fMRI and upper-extremity function: The effect of dual-tasking. 2017 Junior Investigators Forum, Health Sciences. Tucson: University of Arizona.
• Chou, Y. (2016, September). Frontoparietal activation during visual conjunction search: Effects of bottom-up guidance and adult age. Cognitive Aging Conference. Atlanta, GA.