Xunda Wang

All Publications

• Olfactory cortical outputs recruit and shape distinct brain-wide spatiotemporal networks Elife Ma, T., Wang, X., Lin, X., Wen, J., Xie, L., Khong, P., Cao, P., Wu, E., Leong, A. 2024

  View details for DOI 10.7554/eLife.101189.1

• Functional MRI reveals brain-wide actions of thalamically-initiated oscillatory activities on associative memory consolidation. Nature communications Wang, X., Leong, A. T., Tan, S. Z., Wong, E. C., Liu, Y., Lim, L. W., Wu, E. X. 2023; 14 (1): 2195

  Abstract

  As a key oscillatory activity in the brain, thalamic spindle activities are long believed to support memory consolidation. However, their propagation characteristics and causal actions at systems level remain unclear. Using functional MRI (fMRI) and electrophysiology recordings in male rats, we found that optogenetically-evoked somatosensory thalamic spindle-like activities targeted numerous sensorimotor (cortex, thalamus, brainstem and basal ganglia) and non-sensorimotor limbic regions (cortex, amygdala, and hippocampus) in a stimulation frequency- and length-dependent manner. Thalamic stimulation at slow spindle frequency (8 Hz) and long spindle length (3 s) evoked the most robust brain-wide cross-modal activities. Behaviorally, evoking these global cross-modal activities during memory consolidation improved visual-somatosensory associative memory performance. More importantly, parallel visual fMRI experiments uncovered response potentiation in brain-wide sensorimotor and limbic integrative regions, especially superior colliculus, periaqueductal gray, and insular, retrosplenial and frontal cortices. Our study directly reveals that thalamic spindle activities propagate in a spatiotemporally specific manner and that they consolidate associative memory by strengthening multi-target memory representation.

  View details for DOI 10.1038/s41467-023-37682-8

  View details for PubMedID 37069169

  View details for PubMedCentralID PMC10110623

• Astrocyte dysfunction drives abnormal resting-state functional connectivity in depression. Science advances Liu, J., Mo, J. W., Wang, X., An, Z., Zhang, S., Zhang, C. Y., Yi, P., Leong, A. T., Ren, J., Chen, L. Y., Mo, R., Xie, Y., Feng, Q., Chen, W., Gao, T. M., Wu, E. X., Feng, Y., Cao, X. 2022; 8 (46): eabo2098

  Abstract

  Major depressive disorder (MDD) is a devastating mental disorder that affects up to 17% of the population worldwide. Although brain-wide network-level abnormalities in MDD patients via resting-state functional magnetic resonance imaging (rsfMRI) exist, the mechanisms underlying these network changes are unknown, despite their immense potential for depression diagnosis and management. Here, we show that the astrocytic calcium-deficient mice, inositol 1,4,5-trisphosphate-type-2 receptor knockout mice (Itpr2-/- mice), display abnormal rsfMRI functional connectivity (rsFC) in depression-related networks, especially decreased rsFC in medial prefrontal cortex (mPFC)-related pathways. We further uncover rsFC decreases in MDD patients highly consistent with those of Itpr2-/- mice, especially in mPFC-related pathways. Optogenetic activation of mPFC astrocytes partially enhances rsFC in depression-related networks in both Itpr2-/- and wild-type mice. Optogenetic activation of the mPFC neurons or mPFC-striatum pathway rescues disrupted rsFC and depressive-like behaviors in Itpr2-/- mice. Our results identify the previously unknown role of astrocyte dysfunction in driving rsFC abnormalities in depression.

  View details for DOI 10.1126/sciadv.abo2098

  View details for PubMedID 36383661

  View details for PubMedCentralID PMC9668300

• Neural activity temporal pattern dictates long-range propagation targets. NeuroImage Leong, A. T., Wang, X., Wong, E. C., Dong, C. M., Wu, E. X. 2021; 235: 118032

  Abstract

  Brain possesses a complex spatiotemporal architecture for efficient information processing and computing. However, it remains unknown how neural signal propagates to its intended targets brain-wide. Using optogenetics and functional MRI, we arbitrarily initiated various discrete neural activity pulse trains with different temporal patterns and revealed their distinct long-range propagation targets within the well-defined, topographically organized somatosensory thalamo-cortical circuit. We further observed that such neural activity propagation over long range could modulate brain-wide sensory functions. Electrophysiological analysis indicated that distinct propagation pathways arose from system level neural adaptation and facilitation in response to the neural activity temporal characteristics. Together, our findings provide fundamental insights into the long-range information transfer and processing. They directly support that temporal coding underpins the whole brain functional architecture in presence of the vast and relatively static anatomical architecture.

  View details for DOI 10.1016/j.neuroimage.2021.118032

  View details for PubMedID 33836268

• Thalamic low frequency activity facilitates resting-state cortical interhemispheric MRI functional connectivity. NeuroImage Wang, X. n., Leong, A. T., Chan, R. W., Wu, E. X. 2019

  Abstract

  Blood-oxygen-level-dependent (BOLD) resting-state functional MRI (rsfMRI) has emerged as a valuable tool to map complex brain-wide functional networks, predict cognitive performance and identify biomarkers for neurological diseases. However, interpreting these findings poses challenges, as the neural basis of rsfMRI connectivity remains poorly understood. The thalamus serves as a relay station and modulates diverse long-range cortical functional integrations, yet few studies directly interrogate its role in brain-wide rsfMRI connectivity. Utilizing a multi-modal approach of rsfMRI, optogenetic stimulation and multi-depth cortical electrophysiology recording, we examined whether and how the somatosensory thalamus contributes to cortical interhemispheric rsfMRI connectivity. We found that low frequency (1 Hz) optogenetic stimulation of somatosensory-specific ventral posteromedial (VPM) thalamocortical excitatory neurons increased the interhemispheric rsfMRI connectivity in all examined sensory cortices, somatosensory, visual and auditory, and the local intrahemispheric BOLD activity at infraslow frequency (0.01-0.1 Hz). In parallel, multi-depth local field potential recordings at bilateral primary somatosensory cortices revealed increased interhemispheric correlations of low frequency neural oscillations (i.e., mainly < 10 Hz) at all cortical layers. Meanwhile, pharmacologically inhibiting VPM thalamocortical neurons decreased interhemispheric rsfMRI connectivity and local intrahemispheric infraslow BOLD activity in all sensory cortices. Taken together, our findings demonstrate that low frequency activities in the thalamo-cortical network contribute to brain-wide rsfMRI connectivity, highlighting the thalamus as a pivotal region that underlies rsfMRI connectivity.

  View details for DOI 10.1016/j.neuroimage.2019.06.063

  View details for PubMedID 31299370

• Altered dynamic functional connectivity in antagonistic state in first-episode, drug-naïve patients with major depressive disorder. BMC psychiatry Wang, M., Chen, T., He, Z., Chan, L. W., Guo, Q., Cai, S., Duan, J., Zhang, D., Wang, X., Fang, Y., Yang, H. 2024; 24 (1): 909

  Abstract

  Major depressive disorder (MDD) is known to be characterized by disrupted brain functional network connectivity (FNC) patterns, while the dynamic change mode of different functional networks is unclear. This study aimed to characterize specific dynamic alterations pattern on intrinsic FNC in MDD by combining static FNC (sFNC) and dynamic FNC (dFNC).A total of 48 first-episode drug-naïve MDD and 48 matched healthy controls (HCs) were included in this study. The sFNC and dFNC were analyzed using complete time-series and sliding window approach, respectively. Both sFNC and dFNC differences between groups were analyzed and associations between disease severity and aberrant FNC were explored.MDD patients exhibited lower sFNC within and between sensory and motor networks than HC. Four dFNC states were identified, including a globally-weakly-connected state, a cognitive-control-dominated state, a globally-positively-connected state, and an antagonistic state. The antagonistic state was marked by strong positive connections within the sensorimotor domain and their anti-correlations with the executive-motor control domain. Notably, MDD patients exhibited significantly longer dwell time in the globally-weakly-connected state, at the cost of significantly shorter dwell time in the antagonistic state. Further, only the mean dwell time of this antagonistic state was significantly anticorrelated to disease severity measures.Our study highlights the altered dynamics of the antagonistic state as a fundamental aspect of disrupted FNC in early MDD.

  View details for DOI 10.1186/s12888-024-06356-0

  View details for PubMedID 39696016

  View details for PubMedCentralID PMC11653573

• Pushing the limits of low-cost ultra-low-field MRI by dual-acquisition deep learning 3D superresolution. Magnetic resonance in medicine Lau, V., Xiao, L., Zhao, Y., Su, S., Ding, Y., Man, C., Wang, X., Tsang, A., Cao, P., Lau, G. K., Leung, G. K., Leong, A. T., Wu, E. X. 2023; 90 (2): 400-416

  Abstract

  Recent development of ultra-low-field (ULF) MRI presents opportunities for low-power, shielding-free, and portable clinical applications at a fraction of the cost. However, its performance remains limited by poor image quality. Here, a computational approach is formulated to advance ULF MR brain imaging through deep learning of large-scale publicly available 3T brain data.A dual-acquisition 3D superresolution model is developed for ULF brain MRI at 0.055 T. It consists of deep cross-scale feature extraction, attentional fusion of two acquisitions, and reconstruction. Models for T1 -weighted and T2 -weighted imaging were trained with 3D ULF image data sets synthesized from the high-resolution 3T brain data from the Human Connectome Project. They were applied to 0.055T brain MRI with two repetitions and isotropic 3-mm acquisition resolution in healthy volunteers, young and old, as well as patients.The proposed approach significantly enhanced image spatial resolution and suppressed noise/artifacts. It yielded high 3D image quality at 0.055 T for the two most common neuroimaging protocols with isotropic 1.5-mm synthetic resolution and total scan time under 20 min. Fine anatomical details were restored with intrasubject reproducibility, intercontrast consistency, and confirmed by 3T MRI.The proposed dual-acquisition 3D superresolution approach advances ULF MRI for quality brain imaging through deep learning of high-field brain data. Such strategy can empower ULF MRI for low-cost brain imaging, especially in point-of-care scenarios or/and in low-income and mid-income countries.

  View details for DOI 10.1002/mrm.29642

  View details for PubMedID 37010491

• Hippocampus Modulates Vocalizations Responses at Early Auditory Centers. NeuroImage Leong, A. T., Wong, E. C., Wang, X., Wu, E. X. 2023; 270: 119943

  Abstract

  Despite its prominence in learning and memory, hippocampal influence in early auditory processing centers remains unknown. Here, we examined how hippocampal activity modulates sound-evoked responses in the auditory midbrain and thalamus using optogenetics and functional MRI (fMRI) in rodents. Ventral hippocampus (vHP) excitatory neuron stimulation at 5 Hz evoked robust hippocampal activity that propagates to the primary auditory cortex. We then tested 5 Hz vHP stimulation paired with either natural vocalizations or artificial/noise acoustic stimuli. vHP stimulation enhanced auditory responses to vocalizations (with a negative or positive valence) in the inferior colliculus, medial geniculate body, and auditory cortex, but not to their temporally reversed counterparts (artificial sounds) or broadband noise. Meanwhile, pharmacological vHP inactivation diminished response selectivity to vocalizations. These results directly reveal the large-scale hippocampal participation in natural sound processing at early centers of the ascending auditory pathway. They expand our present understanding of hippocampus in global auditory networks.

  View details for DOI 10.1016/j.neuroimage.2023.119943

  View details for PubMedID 36828157

• Optogenetic fMRI interrogation of brain-wide central vestibular pathways PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Leong, A. L., Gu, Y., Chan, Y., Zheng, H., Dong, C. M., Chan, R. W., Wang, X., Liu, Y., Tan, L., Wu, E. X. 2019; 116 (20): 10122–29

  Abstract

  Blood oxygen level-dependent functional MRI (fMRI) constitutes a powerful neuroimaging technology to map brain-wide functions in response to specific sensory or cognitive tasks. However, fMRI mapping of the vestibular system, which is pivotal for our sense of balance, poses significant challenges. Physical constraints limit a subject's ability to perform motion- and balance-related tasks inside the scanner, and current stimulation techniques within the scanner are nonspecific to delineate complex vestibular nucleus (VN) pathways. Using fMRI, we examined brain-wide neural activity patterns elicited by optogenetically stimulating excitatory neurons of a major vestibular nucleus, the ipsilateral medial VN (MVN). We demonstrated robust optogenetically evoked fMRI activations bilaterally at sensorimotor cortices and their associated thalamic nuclei (auditory, visual, somatosensory, and motor), high-order cortices (cingulate, retrosplenial, temporal association, and parietal), and hippocampal formations (dentate gyrus, entorhinal cortex, and subiculum). We then examined the modulatory effects of the vestibular system on sensory processing using auditory and visual stimulation in combination with optogenetic excitation of the MVN. We found enhanced responses to sound in the auditory cortex, thalamus, and inferior colliculus ipsilateral to the stimulated MVN. In the visual pathway, we observed enhanced responses to visual stimuli in the ipsilateral visual cortex, thalamus, and contralateral superior colliculus. Taken together, our imaging findings reveal multiple brain-wide central vestibular pathways. We demonstrate large-scale modulatory effects of the vestibular system on sensory processing.

  View details for DOI 10.1073/pnas.1812453116

  View details for Web of Science ID 000467804000066

  View details for PubMedID 31028140

  View details for PubMedCentralID PMC6525493

• Low-frequency hippocampal-cortical activity drives brain-wide resting-state functional MRI connectivity. Proceedings of the National Academy of Sciences of the United States of America Chan, R. W., Leong, A. T., Ho, L. C., Gao, P. P., Wong, E. C., Dong, C. M., Wang, X., He, J., Chan, Y. S., Lim, L. W., Wu, E. X. 2017; 114 (33): E6972-E6981

  Abstract

  The hippocampus, including the dorsal dentate gyrus (dDG), and cortex engage in bidirectional communication. We propose that low-frequency activity in hippocampal-cortical pathways contributes to brain-wide resting-state connectivity to integrate sensory information. Using optogenetic stimulation and brain-wide fMRI and resting-state fMRI (rsfMRI), we determined the large-scale effects of spatiotemporal-specific downstream propagation of hippocampal activity. Low-frequency (1 Hz), but not high-frequency (40 Hz), stimulation of dDG excitatory neurons evoked robust cortical and subcortical brain-wide fMRI responses. More importantly, it enhanced interhemispheric rsfMRI connectivity in various cortices and hippocampus. Subsequent local field potential recordings revealed an increase in slow oscillations in dorsal hippocampus and visual cortex, interhemispheric visual cortical connectivity, and hippocampal-cortical connectivity. Meanwhile, pharmacological inactivation of dDG neurons decreased interhemispheric rsfMRI connectivity. Functionally, visually evoked fMRI responses in visual regions also increased during and after low-frequency dDG stimulation. Together, our results indicate that low-frequency activity robustly propagates in the dorsal hippocampal-cortical pathway, drives interhemispheric cortical rsfMRI connectivity, and mediates visual processing.

  View details for DOI 10.1073/pnas.1703309114

  View details for PubMedID 28760982

  View details for PubMedCentralID PMC5565425

• Biological Computation Indexes of Brain Oscillations in Unattended Facial Expression Processing Based on Event-Related Synchronization/Desynchronization. Computational and mathematical methods in medicine Yu, B., Ma, L., Li, H., Zhao, L., Bo, H., Wang, X. 2016; 2016: 8958750

  Abstract

  Estimation of human emotions from Electroencephalogram (EEG) signals plays a vital role in affective Brain Computer Interface (BCI). The present study investigated the different event-related synchronization (ERS) and event-related desynchronization (ERD) of typical brain oscillations in processing Facial Expressions under nonattentional condition. The results show that the lower-frequency bands are mainly used to update Facial Expressions and distinguish the deviant stimuli from the standard ones, whereas the higher-frequency bands are relevant to automatically processing different Facial Expressions. Accordingly, we set up the relations between each brain oscillation and processing unattended Facial Expressions by the measures of ERD and ERS. This research first reveals the contributions of each frequency band for comprehension of Facial Expressions in preattentive stage. It also evidences that participants have emotional experience under nonattentional condition. Therefore, the user's emotional state under nonattentional condition can be recognized in real time by the ERD/ERS computation indexes of different frequency bands of brain oscillations, which can be used in affective BCI to provide the user with more natural and friendly ways.

  View details for DOI 10.1155/2016/8958750

  View details for PubMedID 27471545

  View details for PubMedCentralID PMC4947680

• The method of auditory cognitive control feature extraction of cerebral cortex potential for auditory modality speech conflicting ACTA ACUSTICA Yu, B., Li, H., Ma, L., Wang, X. 2016

  View details for DOI 10.15949/j.cnki.0371-0025.2016.06.012

• The Complex Pre-Execution Stage of Auditory Cognitive Control: ERPs Evidence from Stroop Tasks. PloS one Yu, B., Wang, X., Ma, L., Li, L., Li, H. 2015; 10 (9): e0137649

  Abstract

  Cognitive control has been extensively studied from Event-Related Potential (ERP) point of view in visual modality using Stroop paradigms. Little work has been done in auditory Stroop paradigms, and inconsistent conclusions have been reported, especially on the conflict detection stage of cognitive control. This study investigated the early ERP components in an auditory Stroop paradigm, during which participants were asked to identify the volume of spoken words and ignore the word meanings. A series of significant ERP components were revealed that distinguished incongruent and congruent trials: two declined negative polarity waves (the N1 and the N2) and three declined positive polarity wave (the P1, the P2 and the P3) over the fronto-central area for the incongruent trials. These early ERP components imply that both a perceptual stage and an identification stage exist in the auditory Stroop effect. A 3-stage cognitive control model was thus proposed for a more detailed description of the human cognitive control mechanism in the auditory Stroop tasks.

  View details for DOI 10.1371/journal.pone.0137649

  View details for PubMedID 26368570

  View details for PubMedCentralID PMC4569364

• Semantic-Physically Conflicting Speech Perception and Human Cognitive Principle Inspired ASR System Design Wang, X., Li, H., Ma, L., Yu, B., Li, J. B. IEEE. 2015: 1094-1099

  View details for DOI 10.1109/IMCCC.2015.236

  View details for Web of Science ID 000380403700230

• Automatic brain cognitive control detection method International Conference on Software Intelligence Technologies and Applications & International Conference on Frontiers of Internet of Things 2014 Yu, B., Li, H., Ma, L., Wang, X. 2014

  View details for DOI 10.1049/cp.2014.1571