Xiao-Jing Wang

Xiao-Jing Wang
New York University | NYU

About

180
Publications
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Publications

Publications (180)
Preprint
Based on quantitative cyto- and receptor architectonic analyses, we identified 35 prefrontal areas and introduced a novel subdivision of Walker’s areas 10, 9, 8B and 46. Statistical analysis of receptor densities revealed regional differences in lateral and ventrolateral prefrontal cortex. Since structural and functional organization of subdivision...
Article
Full-text available
Neural activity underlying working memory is not a local phenomenon but distributed across multiple brain regions. To elucidate the circuit mechanism of such distributed activity, we developed an anatomically constrained computational model of large-scale macaque cortex. We found that mnemonic internal states may emerge from inter-areal reverberati...
Preprint
A growing body of evidence suggests that conscious perception of a sensory stimulus triggers an all-or-none activity across multiple cortical areas, a phenomenon called 'ignition'. In contrast, the same stimulus, when undetected, induces only transient activity. In this work, we report a large-scale model of the macaque cortex based on recently qua...
Article
How the brain stores a sequence in memory remains largely unknown. We investigated the neural code underlying sequence working memory using two-photon calcium imaging to record thousands of neurons in the prefrontal cortex of macaque monkeys memorizing and then reproducing a sequence of locations after a delay. We discovered a regular geometrical o...
Article
The synaptic balance between excitation and inhibition (E/I balance) is a fundamental principle of cortical circuits, and disruptions in E/I balance are commonly linked to cognitive deficits such as impaired decision making. Explanatory gaps remain in a mechanistic understanding of how E/I balance contributes to cognitive computations, and how E/I...
Article
Balancing instant gratification versus delayed but better gratification is important for optimizing survival and reproductive success. Although delayed gratification has been studied through human psychological and brain activity monitoring and animal research, little is known about its neural basis. We successfully trained mice to perform a waitin...
Article
Half a century ago persistent spiking activity in the neocortex was discovered to be a neural substrate of working memory. Since then scientists have sought to understand this core cognitive function across biological and computational levels. Studies are reviewed here that cumulatively lend support to a synaptic theory of recurrent circuits for mn...
Preprint
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Learning-to-learn, a progressive acceleration of learning while solving a series of similar problems, represents a core process of knowledge acquisition that draws attention in both neuroscience and artificial intelligence. To investigate its underlying brain mechanism, we trained a recurrent neural network model on arbitrary sensorimotor mappings....
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Dopamine is required for working memory, but how it modulates the large-scale cortex is unknown. Here, we report that dopamine receptor density per neuron, measured by autoradiography, displays a macroscopic gradient along the macaque cortical hierarchy. This gradient is incorporated in a connectome-based large-scale cortex model endowed with multi...
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The marmoset monkey has become an important primate model in Neuroscience. Here, we characterize salient statistical properties of interareal connections of the marmoset cerebral cortex, using data from retrograde tracer injections. We found that the connectivity weights are highly heterogeneous, spanning 5 orders of magnitude, and are log-normally...
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We are constantly faced with decisions between alternatives defined by multiple attributes, necessitating an evaluation and integration of different information sources. Time-varying signals in multiple brain areas are implicated in decision-making; but we lack a rigorous biophysical description of how basic circuit properties, such as excitatory-i...
Preprint
Balancing instant gratification versus delayed, but better gratification is important for optimizing survival and reproductive success. Although psychologists and neuroscientists have long attempted to study delayed gratification through human psychological and brain activity monitoring, and animal research, little is known about its neural basis....
Preprint
Full-text available
Dynamics and functions of neural circuits depend on synaptic interactions mediated by receptors. Therefore, a comprehensive map of receptor organization is needed to understand how different functions may emerge across distinct cortical regions. Here we use in-vitro receptor autoradiography to measure the density of 14 neurotransmitter receptor typ...
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Hierarchy is a major organizational principle of the cortex and underscores modern computational theories of cortical function. The local microcircuit amplifies long-distance inter-areal input, which show distance-dependent changes in their laminar profiles. Statistical modeling of these changes in laminar profiles demonstrates that inputs from mul...
Article
Databases of consistent, directed- and weighted inter-areal connectivity for mouse, macaque and marmoset monkeys have recently become available and begun to be used to build structural and dynamical models. A structural hierarchy can be defined based by laminar patterns of cortical connections. A large-scale dynamical model of the macaque cortex en...
Article
Artificial neural networks (ANNs) are essential tools in machine learning that have drawn increasing attention in neuroscience. Besides offering powerful techniques for data analysis, ANNs provide a new approach for neuroscientists to build models for complex behaviors, heterogeneous neural activity, and circuit connectivity, as well as to explore...
Preprint
Full-text available
Dopamine is critical for working memory. However, its effects throughout the large-scale primate cortex are poorly understood. Here we report that dopamine receptor density per neuron, measured by receptor autoradiography in the macaque monkey cortex, displays a macroscopic gradient along the cortical hierarchy. We developed a connectome- and bioph...
Article
Full-text available
The human brain is a biological organ, weighing about three pounds or 1.4 kg, that determines our behaviors, thoughts, emotions and consciousness. Although comprising only 2% of the total body weight, the brain consumes about 20% of the oxygen entering the body. With the expensive energy demand, the brain enables us to perceive and act upon the ext...
Preprint
Full-text available
Databases of directed- and weighted- connectivity for mouse, macaque and marmoset monkeys, have recently become available and begun to be used to build dynamical models. A hierarchical organization can be defined based on laminar patterns of cortical connections, possibly improved by thalamocortical projections. A large-scale model of the macaque c...
Preprint
Full-text available
In contrast to feedforward architecture commonly used in deep networks at the core of today’s AI revolution, the biological cortex is endowed with an abundance of feedback projections. Feedback signaling is often difficult to differentially identify, and its computational roles remain poorly understood. Here, we investigated a cognitive phenomenon,...
Preprint
Full-text available
Artificial neural networks (ANNs) are essential tools in machine learning that are increasingly used for building computational models in neuroscience. Besides being powerful techniques for data analysis, ANNs provide a new approach for neuroscientists to build models that capture complex behaviors, neural activity and connectivity, as well as to e...
Preprint
Full-text available
Hierarchy is a major organizational principle of the cortex and underscores modern computational theories of cortical function. The local microcircuit amplifies long-distance inter-areal input, which show distance-dependent changes in their laminar profiles. Statistical modeling of these changes in laminar profiles demonstrates that inputs from mul...
Article
With advances in connectomics, transcriptome and neurophysiological technologies, the neuroscience of brain-wide neural circuits is poised to take off. A major challenge is to understand how a vast diversity of functions is subserved by parcellated areas of mammalian neocortex composed of repetitions of a canonical local circuit. Areas of the cereb...
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Full-text available
We investigated two-attribute, two-alternative decision-making in a hierarchical neural network with three layers: an input layer encoding choice alternative attribute values; an intermediate layer of modules processing separate attributes; and a choice layer producing the decision. Depending on intermediate layer excitatory-inhibitory (E/I) tone,...
Preprint
Full-text available
Working memory, the brain's ability to retain and manipulate information internally, has been traditionally associated with persistent neural firing in localized brain areas such as those in the frontal cortex (Fuster 1973, Funahashi et al., 1989; Goldman-Rakic 1995; Romo et al., 1999; Rigotti et al., 2013; Kopec et al., 2015; Inagaki et al., 2019)...
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Analyses of idealized feedforward networks suggest that several conditions have to be satisfied in order for activity to propagate faithfully across layers. Verifying these concepts experimentally has been difficult owing to the vast number of variables that must be controlled. Here, we cultured cortical neurons in a chamber with sequentially conne...
Article
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Recently it has been proposed that information in working memory (WM) may not always be stored in persistent neuronal activity but can be maintained in ‘activity-silent’ hidden states, such as synaptic efficacies endowed with short-term synaptic plasticity. To test this idea computationally, we investigated recurrent neural network models trained t...
Article
The primate cerebral cortex displays a hierarchy that extends from primary sensorimotor to association areas, supporting increasingly integrated function underpinned by a gradient of heterogeneity in the brain’s microcircuits. The extent to which these hierarchical gradients are unique to primate or may reflect a conserved mammalian principle of br...
Article
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The brain has the ability to flexibly perform many tasks, but the underlying mechanism cannot be elucidated in traditional experimental and modeling studies designed for one task at a time. Here, we trained single network models to perform 20 cognitive tasks that depend on working memory, decision making, categorization, and inhibitory control. We...
Preprint
Full-text available
The primate cerebral cortex displays a hierarchical organization that extends from primary sensorimotor to association areas, supporting increasingly integrated function that is underpinned by a gradient of heterogeneity in the brain's microcircuits. The extent to which these properties of brain organization are unique to primate or may be conserve...
Preprint
Full-text available
Recently it has been proposed that information in short-term memory may not always be stored in persistent neuronal activity, but can be maintained in "activity-silent" hidden states such as synaptic efficacies endowed with short-term plasticity (STP). However, working memory involves manipulation as well as maintenance of information in the absenc...
Preprint
The manner in which information is transferred and transformed across brain regions is yet unclear. Theoretical analyses of idealized feedforward networks suggest that several conditions have to be satisfied in order for activity to propagate faithfully across layers. Verifying these concepts experimentally in networks has not been possible owing t...
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Full-text available
Reliable signal transmission represents a fundamental challenge for cortical systems, which display a wide range of weights of feedforward and feedback connections among heterogeneous areas. We re-examine the question of signal transmission across the cortex in network models based on recently available mesoscopic, directed‐ and weighted-inter-area...
Preprint
Full-text available
A neural system has the ability to flexibly perform many tasks, but the underlying mechanism cannot be elucidated in traditional experimental and modeling studies designed for one task at a time. Here, we trained a single network model to perform 20 cognitive tasks that may involve working memory, decision-making, categorization and inhibitory cont...
Preprint
Full-text available
Pyramidal cells and interneurons expressing parvalbumin, somatostatin, or vasoactive intestinal peptide show cell type-specific connectivity patterns leading to a canonical microcircuit across cortex. Dissecting the dynamics of this microcircuit is essential to our understanding of the mammalian cortex. However, experiments recording from this circ...
Article
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Schizophrenia research is plagued by enormous challenges in integrating and analyzing large datasets and difficulties developing formal theories related to the etiology, pathophysiology, and treatment of this disorder. Computational psychiatry provides a path to enhance analyses of these large and complex datasets and to promote the development and...
Article
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Decision making involves dynamic interplay between internal judgements and external perception, which has been investigated in delayed match-to-category (DMC) experiments. Our analysis of neural recordings shows that, during DMC tasks, LIP and PFC neurons demonstrate mixed, time-varying, and heterogeneous selectivity, but previous theoretical work...
Preprint
Working memory (WM) and decision making (DM) are fundamental cognitive functions involving a distributed interacting network of brain areas, with the posterior parietal and prefrontal cortices (PPC and PFC) at the core. However, the shared and distinct roles of these areas and the nature of their coordination in cognitive function remain poorly und...
Preprint
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Background Disruption of the synaptic balance between excitation and inhibition (E/I balance) in cortical circuits is a leading hypothesis for pathophysiologies of neuropsychiatric disorders, such as schizophrenia. However, it is poorly understood how synaptic E/I disruptions propagate upward to induce cognitive deficits, including impaired decisio...
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The functional optimization of neural ensembles is central to human higher cognitive functions. When the functions through which neural activity is tuned fail to develop or break down, symptoms and cognitive impairments arise. This review will consider ways that disturbances in the balance of excitation and inhibition might develop and be expressed...
Article
Working memory (WM) is a cognitive function for temporary maintenance and manipulation of information, which requires conversion of stimulus-driven signals into internal representations that are maintained across seconds-long mnemonic delays. Within primate prefrontal cortex (PFC), a critical node of the brain's WM network, neurons show stimulus-se...
Chapter
Clinical heterogeneity presents important challenges to optimizing psychiatric diagnoses and treatments. Patients clustered within current diagnostic schema vary widely on many features of their illness, including their responses to treatments. As outlined by the American Psychiatric Association Diagnostic and Statistical Manual (DSM), psychiatric...
Article
Schizophrenia is associated with severe cognitive deficits, including impaired working memory (WM). A neural mechanism that may contribute to WM impairment is the disruption in excitation-inhibition (E/I) balance in cortical microcircuits. It remains unknown, however, how these alterations map onto quantifiable behavioral deficits in patients. Base...
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Automatic responses enable us to react quickly and effortlessly, but they often need to be inhibited so that an alternative, voluntary action can take place. To investigate the brain mechanism of controlled behavior, we investigated a biologically-based network model of spiking neurons for inhibitory control. In contrast to a simple race between pr...
Data
Comparison of the observed superior colliculus (SC) activity and the saccade neuron activity in the model. A. Observed firing rates in the SC contralateral to the saccade direction in prosaccade trials (thick solid line) and antisaccade trials (dashed line). B. Same as in A but for activity produced by the model. C. Observed firing rates in the SC...
Data
Comparison of the observed visual neurons in supplementary eye fields (SEF) and the neurons in the visual layer of the model. A. An observed visual neuron exhibited stronger responses in antisaccade than in prosaccade. B. Another observed visual neuron with an opposite trend. C Neurons in the inverted map of the model exhibit stronger visual respon...
Data
Comparison of the observed movement neurons in supplementary eye fields (SEF) and the neurons in the decision layer of the model. A. Observed SEF neuron activity in the correct prosaccades (YYy) and correct antisaccades (NYy) in the preferred direction. (Adapted from “Amador N, Schlag-Rey M, Schlag J. Primate antisaccade. II. supplementary eye fiel...
Data
Comparison of observed and model-produced reaction distribution. A. Observed reaction time distributions of prosaccade, antisaccade and erroneous prosaccade (shown as the black histograms below the abscissa) made in antisaccade trials in overlap and gap paradigms for two monkeys. (Adapted from “Everling S, Dorris MC, Klein RM, Munoz DP. Role of pri...
Preprint
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Trained neural network models, which exhibit many features observed in neural recordings from behaving animals and whose activity and connectivity can be fully analyzed, may provide insights into neural mechanisms. In contrast to commonly used methods for supervised learning from graded error signals, however, animals learn from reward feedback on...
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Full-text available
Interactions between top-down and bottom-up processes in the cerebral cortex hold the key to understanding predictive coding, executive control and a gamut of other brain functions. The underlying circuit mechanism, however, remains poorly understood and represents a major challenge in neuroscience. In the present work we tackled this problem using...
Preprint
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In this work we propose that a disinhibitory circuit motif, which recently gained experimental support, can instantiate flexible routing of information flow along selective pathways in a complex system of cortical areas according to behavioral demands (pathway-specific gating). We developed a network model of pyramidal neurons and three classes of...
Preprint
The power spectrum of brain electric field potential recordings is dominated by an arrhythmic broadband signal but a mechanistic account of its underlying neural network dynamics is lacking. Here we show how the broadband power spectrum of field potential recordings can be explained by a simple random network of nodes near criticality. Such a recur...
Article
Schizophrenia may involve an elevated excitation/inhibition (E/I) ratio in cortical microcircuits. It remains unknown how this regulatory disturbance maps onto neuroimaging findings. To address this issue, we implemented E/I perturbations within a neural model of large-scale functional connectivity, which predicted hyperconnectivity following E/I e...
Article
Full-text available
Our ability to learn a wide range of behavioral tasks is essential for responding appropriately to sensory stimuli according to behavioral demands, but the underlying neural mechanism has been rarely examined by neurophysiological recordings in the same subjects across learning. To understand how learning new behavioral tasks affects neuronal repre...
Article
We developed a large-scale dynamical model of the macaque neocortex, which is based on recently acquired directed- and weighted-connectivity data from tract-tracing experiments, and which incorporates heterogeneity across areas. A hierarchy of timescales naturally emerges from this system: sensory areas show brief, transient responses to input (app...
Article
Full-text available
Evaluation of confidence about one's knowledge is key to the brain's ability to monitor cognition. To investigate the neural mechanism of confidence assessment, we examined a biologically realistic spiking network model and found that it reproduced salient behavioral observations and single-neuron activity data from a monkey experiment designed to...
Article
A hallmark of flexible behavior is the brain's ability to dynamically adjust speed and accuracy in decision-making. Recent studies suggested that such adjustments modulate not only the decision threshold, but also the rate of evidence accumulation. However, the underlying neuronal-level mechanism of the rate change remains unclear. In this work, us...
Preprint
We developed a large-scale dynamical model of the macaque neocortex based on recent quantitative connectivity data. A hierarchy of timescales naturally emerges from this system: sensory areas show brief, transient responses to input (appropriate for sensory processing), whereas association areas integrate inputs over time and exhibit persistent act...
Article
Full-text available
The ability to categorize stimuli into discrete behaviourally relevant groups is an essential cognitive function. To elucidate the neural mechanisms underlying categorization, we constructed a cortical circuit model that is capable of learning a motion categorization task through reward-dependent plasticity. Here we show that stable category repres...
Article
The basal ganglia (BG) play an important role in motor control, reinforcement learning, and perceptual decision making. Modeling and experimental evidence suggest that, in a speed-accuracy tradeoff, the corticostriatal pathway can adaptively adjust a decision threshold (the amount of information needed to make a choice). In this study, we go beyond...
Article
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Strong evidence implicates prefrontal cortex (PFC) as a major source of functional impairment in severe mental illness such as schizophrenia. Numerous schizophrenia studies report deficits in PFC structure, activation, and functional connectivity in patients with chronic illness, suggesting that deficient PFC functional connectivity occurs in this...
Article
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Specialization and hierarchy are organizing principles for primate cortex, yet there is little direct evidence for how cortical areas are specialized in the temporal domain. We measured timescales of intrinsic fluctuations in spiking activity across areas and found a hierarchical ordering, with sensory and prefrontal areas exhibiting shorter and lo...
Article
Psychiatric disorders such as autism and schizophrenia, arise from abnormalities in brain systems that underlie cognitive, emotional, and social functions. The brain is enormously complex and its abundant feedback loops on multiple scales preclude intuitive explication of circuit functions. In close interplay with experiments, theory and computatio...
Article
Recent anatomical tracing studies have yielded substantial amounts of data on the areal connectivity underlying distributed processing in cortex, yet the fundamental principles that govern the large-scale organization of cortex remain unknown. Here we show that functional similarity between areas as defined by the pattern of shared inputs or output...
Article
Recent studies have shown that reverberation underlying mnemonic persistent activity must be slow, to ensure the stability of a working memory system and to give rise to long neural transients capable of accumulation of information over time. Is the slower the underlying process, the better? To address this question, we investigated 3 slow biophysi...
Article
Small-world networks---complex networks characterized by a combination of high clustering and short path lengths---are widely studied using the paradigmatic model of Watts and Strogatz (WS). Although the WS model is already quite minimal and intuitive, we describe an alternative formulation of the WS model in terms of a distance-dependent probabili...
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Neuropsychiatric conditions like schizophrenia display a complex neurobiology, which has long been associated with distributed brain dysfunction. However, no investigation has tested whether schizophrenia shows alterations in global brain signal (GS), a signal derived from functional MRI and often discarded as a meaningless baseline in many studies...