Publications by authors named "Zhe Sage Chen"

Making adaptive decisions in complex environments requires appropriately identifying sources of error. The frontal cortex is critical for adaptive decisions, but its neurons show mixed selectivity to task features and their uncertainty estimates, raising the question of how errors are attributed to their most likely causes. Here, by recording neural responses from tree shrews (Tupaia belangeri) performing a hierarchical decision task with rule reversals, we find that the mediodorsal thalamus independently represents cueing and rule uncertainty.

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Advances in closed-loop neural interfaces and neuromodulation have offered a potentially effective and non-addictive treatment for chronic pain. These interfaces link neural sensors with device outputs to provide temporally precise stimulation. We discuss challenges and trends of state-of-the-art neural interfaces for treating pain in animal models and human pilot trials.

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Identifying directed spectral information flow between multivariate time series is important for many applications in finance, climate, geophysics and neuroscience. Spectral Granger causality (SGC) is a prediction-based measure characterizing directed information flow at specific oscillatory frequencies. However, traditional vector autoregressive (VAR) approaches are insufficient to assess SGC when time series have mixed frequencies (MF) or are coupled by nonlinearity.

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Recent advances in machine learning have led to revolutionary breakthroughs in computer games, image and natural language understanding, and scientific discovery. Foundation models and large-scale language models (LLMs) have recently achieved human-like intelligence thanks to BigData. With the help of self-supervised learning (SSL) and transfer learning, these models may potentially reshape the landscapes of neuroscience research and make a significant impact on the future.

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Distributed hypothalamic-midbrain neural circuits help orchestrate complex behavioral responses during social interactions. Given rapid advances in optical imaging, it is a fundamental question how population-averaged neural activity measured by multi-fiber photometry (MFP) for calcium fluorescence signals correlates with social behaviors is a fundamental question. This paper aims to investigate the correspondence between MFP data and social behaviors.

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High-speed wide-field fluorescence microscopy has the potential to capture biological processes with exceptional spatiotemporal resolution. However, conventional cameras suffer from low signal-to-noise ratio at high frame rates, limiting their ability to detect faint fluorescent events. Here, we introduce an image sensor where each pixel has individually programmable sampling speed and phase, so that pixels can be arranged to simultaneously sample at high speed with a high signal-to-noise ratio.

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Distributed hypothalamic-midbrain neural circuits orchestrate complex behavioral responses during social interactions. How population-averaged neural activity measured by multi-fiber photometry (MFP) for calcium fluorescence signals correlates with social behaviors is a fundamental question. We propose a state-space analysis framework to characterize mouse MFP data based on dynamic latent variable models, which include continuous-state linear dynamical system (LDS) and discrete-state hidden semi-Markov model (HSMM).

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Introduction: Chronic pain negatively impacts a range of sensory and affective behaviors. Previous studies have shown that the presence of chronic pain not only causes hypersensitivity at the site of injury but may also be associated with pain-aversive experiences at anatomically unrelated sites. While animal studies have indicated that the cingulate and prefrontal cortices are involved in this generalized hyperalgesia, the mechanisms distinguishing increased sensitivity at the site of injury from a generalized site-nonspecific enhancement in the aversive response to nociceptive inputs are not well known.

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Background: Prefrontal cortical neurons play essential roles in performing rule-dependent tasks and working memory-based decision making.

Methods: Motivated by PFG recordings of task-performing mice, we developed an excitatory-inhibitory spiking recurrent neural network (SRNN) to perform a rule-dependent two-alternative forced choice (2AFC) task. We imposed several important biological constraints onto the SRNN, and adapted spike frequency adaptation (SFA) and SuperSpike gradient methods to train the SRNN efficiently.

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Background: The striatal-pallidal pathway plays an important role in cognitive control and modulation of behaviors. Globus pallidus interna (GPi), as a primary output structure, is crucial in modulating excitation and inhibition. Studies of GPi in psychiatric illnesses are lacking given the technical challenges of examining this small and functionally diverse subcortical structure.

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High-speed wide-field fluorescence microscopy has the potential to capture biological processes with exceptional spatiotemporal resolution. However, conventional cameras suffer from low signal-to-noise ratio at high frame rates, limiting their ability to detect faint fluorescent events. Here, we introduce an image sensor where each pixel has individually programmable sampling speed and phase, so that pixels can be arranged to simultaneously sample at high speed with a high signal-to-noise ratio.

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Machine learning is becoming an increasingly common component of routine data analyses in clinical research. The past decade in pain research has witnessed great advances in human neuroimaging and machine learning. With each finding, the pain research community takes one step closer to uncovering fundamental mechanisms underlying chronic pain and at the same time proposing neurophysiological biomarkers.

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Hippocampal theta (4-10 Hz) oscillations have been identified as traveling waves in both rodents and humans. In freely foraging rodents, the theta traveling wave is a planar wave propagating from the dorsal to ventral hippocampus along the septotemporal axis. Motivated from experimental findings, we develop a spiking neural network of excitatory and inhibitory neurons to generate state-dependent hippocampal traveling waves to improve current mechanistic understanding of propagating waves.

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Injuries of various types occur commonly in the lives of humans and other animals and lead to a pattern of persistent pain and recuperative behaviour that allows safe and effective recovery. In this Perspective, we propose a control-theoretic framework to explain the adaptive processes in the brain that drive physiological post-injury behaviour. We set out an evolutionary and ethological view on how animals respond to injury, illustrating how the behavioural state associated with persistent pain and recuperation may be just as important as phasic pain in ensuring survival.

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Importance: Sleep disorders are one of the most frequent comorbidities in children with autism spectrum disorder (ASD). However, the link between neurodevelopmental effects in ASD children with their underlying sleep microarchitecture is not well understood. An improved understanding of etiology of sleep difficulties and identification of sleep-associated biomarkers for children with ASD can improve the accuracy of clinical diagnosis.

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Neurons in the prefrontal cortex (PFC) can provide top-down regulation of sensory-affective experiences such as pain. Bottom-up modulation of sensory coding in the PFC, however, remains poorly understood. Here, we examined how oxytocin (OT) signaling from the hypothalamus regulates nociceptive coding in the PFC.

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Predictive coding is a computational theory on describing how the brain perceives and acts, which has been widely adopted in sensory processing and motor control. Nociceptive and pain processing involves a large and distributed network of circuits. However, it is still unknown whether this distributed network is completely decentralized or requires networkwide coordination.

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Memory reactivations and replay, widely reported in the hippocampus and cortex across species, have been implicated in memory consolidation, planning, and spatial and skill learning. Technological advances in electrophysiology, calcium imaging, and human neuroimaging techniques have enabled neuroscientists to measure large-scale neural activity with increasing spatiotemporal resolution and have provided opportunities for developing robust analytic methods to identify memory replay. In this article, we first review a large body of historically important and representative memory replay studies from the animal and human literature.

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Pain is known to have sensory and affective components. The sensory pain component is encoded by neurons in the primary somatosensory cortex (S1), whereas the emotional or affective pain experience is in large part processed by neural activities in the anterior cingulate cortex (ACC). The timing of how a mechanical or thermal noxious stimulus triggers activation of peripheral pain fibers is well-known.

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Pain is driven by sensation and emotion, and in turn, it motivates decisions and actions. To fully appreciate the multidimensional nature of pain, we formulate the study of pain within a closed-loop framework of sensory-motor prediction. In this closed-loop cycle, prediction plays an important role, as the interaction between prediction and actual sensory experience shapes pain perception and subsequently, action.

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Article Synopsis
  • Spatially modulated grid cells were identified in the rat's secondary visual cortex (V2) while the rats navigated, but their function and underlying processes are still unclear.
  • A biologically inspired neural network was trained for a 2D navigation task using multiple sensory inputs, revealing grid-like responses in both excitatory and inhibitory units.
  • The study also identified connections between grid patterns and their functionality in various tasks, suggesting V2 grid cells share computational mechanisms for both spatial navigation and visual recognition.
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In light of the National Institute of Mental Health (NIMH)'s Research Domain Criteria (RDoC), the advent of functional neuroimaging, novel technologies and methods provide new opportunities to develop precise and personalized prognosis and diagnosis of mental disorders. Machine learning (ML) and artificial intelligence (AI) technologies are playing an increasingly critical role in the new era of precision psychiatry. Combining ML/AI with neuromodulation technologies can potentially provide explainable solutions in clinical practice and effective therapeutic treatment.

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Article Synopsis
  • * Recent research suggests that grid-like representations may play a crucial role in various perceptual and cognitive tasks, especially those related to movement and mental navigation.
  • * The authors encourage the use of computational modeling to explore grid cell theories and hope that their insights will foster new testable hypotheses in future experiments.
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Effective treatments for chronic pain remain limited. Conceptually, a closed-loop neural interface combining sensory signal detection with therapeutic delivery could produce timely and effective pain relief. Such systems are challenging to develop because of difficulties in accurate pain detection and ultrafast analgesic delivery.

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Objective: Sudden unexpected death in epilepsy (SUDEP) is the leading cause of epilepsy-related mortality. Although lots of effort has been made in identifying clinical risk factors for SUDEP in the literature, there are few validated methods to predict individual SUDEP risk. Prolonged postictal EEG suppression (PGES) is a potential SUDEP biomarker, but its occurrence is infrequent and requires epilepsy monitoring unit admission.

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