All Publications

  • Individual -speci fic and shared representations during episodic memory encoding and retrieval NEUROIMAGE Xiao, X., Zhou, Y., Liu, J., Ye, Z., Yao, L., Zhang, J., Chen, C., Xue, G. 2020; 217: 116909


    Although human memories seem unique to each individual, they are shared to a great extent across individuals. Previous studies have examined, separately, subject-specific and cross-subject shared representations during memory encoding and retrieval, but how shared memories are formed from individually encoded representations is not clearly understood. Using a unique fMRI design involving memory encoding and retrieval, and representational similarity analysis to link representations from different individuals, brain regions, and processing stages, the current study revealed that distributed brain regions showed both subject-specific and shared neural representations during both memory encoding and retrieval. Furthermore, different brain regions showed stage-specific representational strength, with the visual cortex showing greater unique and shared representations during encoding, whereas the left angular gyrus showing greater unique and shared representations during retrieval. The neural representations during encoding were transformed during retrieval, as shown by smaller cross-subject encoding-retrieval similarity (ERS) than cross-subject similarity either during encoding or during retrieval. This cross-subject and cross-stage similarity was found both within and across regions, with strong pattern similarity between the encoded representation in VVC and the retrieved representation in the angular gyrus. Simulation analysis further suggested that these patterns could be achieved by incorporating stage-specific representational strength, and cross-region reinstatement from encoding to retrieval, but not by a common transformation from encoding to retrieval across subjects. Together, our results shed light on how memory representations are encoded and transformed to maintain individual characteristics and at the same time to create shared representations to facilitate interpersonal communication.

    View details for DOI 10.1016/j.neuroimage.2020.116909

    View details for Web of Science ID 000542368700013

    View details for PubMedID 32387627

  • Stanford Accelerated Intelligent Neuromodulation Therapy for Treatment-Resistant Depression. The American journal of psychiatry Cole, E. J., Stimpson, K. H., Bentzley, B. S., Gulser, M. n., Cherian, K. n., Tischler, C. n., Nejad, R. n., Pankow, H. n., Choi, E. n., Aaron, H. n., Espil, F. M., Pannu, J. n., Xiao, X. n., Duvio, D. n., Solvason, H. B., Hawkins, J. n., Guerra, A. n., Jo, B. n., Raj, K. S., Phillips, A. L., Barmak, F. n., Bishop, J. H., Coetzee, J. P., DeBattista, C. n., Keller, J. n., Schatzberg, A. F., Sudheimer, K. D., Williams, N. R. 2020: appiajp201919070720


    New antidepressant treatments are needed that are effective, rapid acting, safe, and tolerable. Intermittent theta-burst stimulation (iTBS) is a noninvasive brain stimulation treatment that has been approved by the U.S. Food and Drug Administration for treatment-resistant depression. Recent methodological advances suggest that the current iTBS protocol might be improved through 1) treating patients with multiple sessions per day at optimally spaced intervals, 2) applying a higher overall pulse dose of stimulation, and 3) precision targeting of the left dorsolateral prefrontal cortex (DLPFC) to subgenual anterior cingulate cortex (sgACC) circuit. The authors examined the feasibility, tolerability, and preliminary efficacy of Stanford Accelerated Intelligent Neuromodulation Therapy (SAINT), an accelerated, high-dose resting-state functional connectivity MRI (fcMRI)-guided iTBS protocol for treatment-resistant depression.Twenty-two participants with treatment-resistant depression received open-label SAINT. fcMRI was used to individually target the region of the left DLPFC most anticorrelated with sgACC in each participant. Fifty iTBS sessions (1,800 pulses per session, 50-minute intersession interval) were delivered as 10 daily sessions over 5 consecutive days at 90% resting motor threshold (adjusted for cortical depth). Neuropsychological testing was conducted before and after SAINT.One participant withdrew, leaving a sample size of 21. Nineteen of 21 participants (90.5%) met remission criteria (defined as a score <11 on the Montgomery-Åsberg Depression Rating Scale). In the intent-to-treat analysis, 19 of 22 participants (86.4%) met remission criteria. Neuropsychological testing demonstrated no negative cognitive side effects.SAINT, an accelerated, high-dose, iTBS protocol with fcMRI-guided targeting, was well tolerated and safe. Double-blinded sham-controlled trials are needed to confirm the remission rate observed in this initial study.

    View details for DOI 10.1176/appi.ajp.2019.19070720

    View details for PubMedID 32252538

  • Stanford Accelerated Intelligent Neuromodulation Therapy (SAINT) Induces Functional Connectivity Changes in Emotion Regulation Brain Areas for MDD Patients bioRxiv Xiao, X. 2019

    View details for DOI 10.1101/672154

  • Reduced Fidelity of Neural Representation Underlies Episodic Memory Decline in Normal Aging. Cerebral cortex (New York, N.Y. : 1991) Zheng, L., Gao, Z., Xiao, X., Ye, Z., Chen, C., Xue, G. 2017: 1-14


    Emerging studies have emphasized the importance of the fidelity of cortical representation in forming enduring episodic memory. No study, however, has examined whether there are age-related reductions in representation fidelity that can explain memory declines in normal aging. Using functional MRI and multivariate pattern analysis, we found that older adults showed reduced representation fidelity in the visual cortex, which accounted for their decreased memory performance even after controlling for the contribution of reduced activation level. This reduced fidelity was specifically due to older adults' poorer item-specific representation, not due to their lower activation level and variance, greater variability in neuro-vascular coupling, or decreased selectivity of categorical representation (i.e., dedifferentiation). Older adults also showed an enhanced subsequent memory effect in the prefrontal cortex based on activation level, and their prefrontal activation was associated with greater fidelity of representation in the visual cortex and better memory performance. The fidelity of cortical representation thus may serve as a promising neural index for better mechanistic understanding of the memory declines and its compensation in normal aging.

    View details for DOI 10.1093/cercor/bhx130

    View details for PubMedID 28591851

  • Transformed Neural Pattern Reinstatement during Episodic Memory Retrieval JOURNAL OF NEUROSCIENCE Xiao, X., Dong, Q., Gao, J., Men, W., Poldrack, R. A., Xue, G. 2017; 37 (11): 2986-2998


    Contemporary models of episodic memory posit that remembering involves the reenactment of encoding processes. Although encoding-retrieval similarity has been consistently reported and linked to memory success, the nature of neural pattern reinstatement is poorly understood. Using high-resolution fMRI on human subjects, our results obtained clear evidence for item-specific pattern reinstatement in the frontoparietal cortex, even when the encoding-retrieval pairs shared no perceptual similarity. No item-specific pattern reinstatement was found in the ventral visual cortex. Importantly, the brain regions and voxels carrying item-specific representation differed significantly between encoding and retrieval, and the item specificity for encoding-retrieval similarity was smaller than that for encoding or retrieval, suggesting different nature of representations between encoding and retrieval. Moreover, cross-region representational similarity analysis suggests that the encoded representation in the ventral visual cortex was reinstated in the frontoparietal cortex during retrieval. Together, these results suggest that, in addition to reinstatement of the originally encoded pattern in the brain regions that perform encoding processes, retrieval may also involve the reinstatement of a transformed representation of the encoded information. These results emphasize the constructive nature of memory retrieval that helps to serve important adaptive functions.SIGNIFICANCE STATEMENT Episodic memory enables humans to vividly reexperience past events, yet how this is achieved at the neural level is barely understood. A long-standing hypothesis posits that memory retrieval involves the faithful reinstatement of encoding-related activity. We tested this hypothesis by comparing the neural representations during encoding and retrieval. We found strong pattern reinstatement in the frontoparietal cortex, but not in the ventral visual cortex, that represents visual details. Critically, even within the same brain regions, the nature of representation during retrieval was qualitatively different from that during encoding. These results suggest that memory retrieval is not a faithful replay of past event but rather involves additional constructive processes to serve adaptive functions.

    View details for DOI 10.1523/JNEUROSCI.2324-16.2017

    View details for Web of Science ID 000397808000017

    View details for PubMedID 28202612

  • Orthographic and Phonological Representations in the Fusiform Cortex. Cerebral cortex (New York, N.Y. : 1991) Zhao, L., Chen, C., Shao, L., Wang, Y., Xiao, X., Chen, C., Yang, J., Zevin, J., Xue, G. 2016: -?


    Mental and neural representations of words are at the core of understanding the cognitive and neural mechanisms of reading. Despite extensive studies, the nature of visual word representation remains highly controversial due to methodological limitations. In particular, it is unclear whether the fusiform cortex contains only abstract orthographic representation, or represents both lower and higher level orthography as well as phonology. Using representational similarity analysis, we integrated behavioral ratings, computational models of reading and visual object recognition, and neuroimaging data to examine the nature of visual word representations in the fusiform cortex. Our results provided clear evidence that the middle and anterior fusiform represented both phonological and orthographic information. Whereas lower level orthographic information was represented at every stage of the ventral visual stream, abstract orthographic information was increasingly represented along the posterior-to-anterior axis. Furthermore, the left and right hemispheres were tuned to high- and low-frequency orthographic information, respectively. These results help to resolve the long-standing debates regarding the role of the fusiform in reading, and have significant implications for the development of psychological, neural, and computational theories of reading.

    View details for PubMedID 27664959

  • Neural pattern similarity underlies the mnemonic advantages for living words CORTEX Xiao, X., Dong, Q., Chen, C., Xue, G. 2016; 79: 99-111


    It has been consistently shown that words representing living things are better remembered than words representing nonliving things, yet the underlying cognitive and neural mechanisms have not been clearly elucidated. The present study used both univariate and multivariate pattern analyses to examine the hypotheses that living words are better remembered because (1) they draw more attention and/or (2) they share more overlapping semantic features. Subjects were asked to study a list of living and nonliving words during a semantic judgment task. An unexpected recognition test was administered 30 min later. We found that subjects recognized significantly more living words than nonliving words. Results supported the overlapping semantic feature hypothesis by showing that (a) semantic ratings showed greater semantic similarity for living words than for nonliving words, (b) there was also significantly greater neural global pattern similarity (nGPS) for living words than for nonliving words in the posterior portion of left parahippocampus (LpPHG), (c) the nGPS in the LpPHG reflected the rated semantic similarity, and also mediated the memory differences between two semantic categories, and (d) greater univariate activation was found for living words than for nonliving words in the left hippocampus (LHIP), which mediated the better memory performance for living words and might reflect greater semantic context binding. In contrast, although living words were processed faster and elicited a stronger activity in the dorsal attention network, these differences did not mediate the animacy effect in memory. Taken together, our results provide strong support to the overlapping semantic features hypothesis, and emphasize the important role of semantic organization in episodic memory encoding.

    View details for DOI 10.1016/j.cortex.2016.03.016

    View details for Web of Science ID 000377315300008

    View details for PubMedID 27093349

  • Neural mechanisms of the spacing effect in episodic memory: A parallel EEG and fMRI study CORTEX Zhao, X., Wang, C., Liu, Q., Xiao, X., Jiang, T., Chen, C., Xue, G. 2015; 69: 76-92


    Although behavioral studies have consistently reported the spacing effect in learning, its cognitive and neural mechanisms are still not clearly elucidated. According to the storage/retrieval strength framework proposed by Bjork (1999; Bjork & Bjork, 1992), which was built on the study-phase retrieval hypothesis and the deficient processing hypothesis, the spacing effect is achieved by reducing memomtary retrieval strength during subsequent repetitions and thus enhancing storage strength. The present study tested this hypothesis with parallel fMRI and EEG. Participants were asked to study 180 words that were repeated three times, with half of the words having an inter-repetition-lag of 1-3 words (i.e., massed learning) and the other half an inter-repetition-lag of 25-35 words (i.e., spaced learning). An unexpected recognition test was administered 24 h after learning. Consistent with Bjork's hypothesis, the EEG data suggested that spaced learning was associated with weaker retrieval strength, as indicated by a reduced familiarity effect in frontal N400. Meanwhile, spaced learning effectively enhanced the encoding process and thus led to stronger storage strength, as indicated by greater fMRI responses during learning in brain regions whose activities were associated with subsequent memory. Interestingly, no direct association was found between repetition priming and episodic memory. These results furthered our understanding of the neural mechanisms underlying the spacing effect.

    View details for DOI 10.1016/j.cortex.2015.04.002

    View details for Web of Science ID 000359330200009

    View details for PubMedID 25989444