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Publications (56)
Background
Alzheimer’s disease (AD) is a serious neurodegenerative disorder without a clear understanding of pathophysiology. Recent experimental data have suggested neuronal excitation-inhibition (E-I) imbalance as an essential element of AD pathology, but E-I imbalance has not been systematically mapped out for either local or large-scale neurona...
Spike timing-based representations of sensory information depend on embedded dynamical frameworks within neuronal networks that establish the rules of local computation and interareal communication. Here, we investigated the dynamical properties of olfactory bulb circuitry in mice of both sexes using microelectrode array recordings from slice and i...
Human brain undergoes rapid growth during the first few years of life. While previous research has employed graph theory to study early brain development, it has mostly focused on the topological attributes of the whole brain. However, examining regional graph-theory features may provide unique insights into the development of cognitive abilities....
Brain wiring redundancy counteracts aging-related cognitive decline by reserving additional communication channels as a neuroprotective mechanism. Such a mechanism plays a potentially important role in maintaining cognitive function during the early stages of neurodegenerative disorders such as Alzheimer's disease (AD). AD is characterized by sever...
Alzheimer′s disease (AD) is a serious neurodegenerative disorder without a clear understanding of the etiology and pathophysiology. Recent experimental data has suggested excitation-inhibition (E-I) imbalance as an essential element and critical regulator of AD pathology, but E-I imbalance has not been systematically mapped out in both local and la...
This paper proposes a deep learning framework to encode subject-specific transformations between facial and bony shapes for orthognathic surgical planning. Our framework involves a bidirectional point-to-point convolutional network (P2P-Conv) to predict the transformations between facial and bony shapes. P2P-Conv is an extension of the state-of-the...
As a newly emerging field, connectomics has greatly advanced our understanding of the wiring diagram and organizational features of the human brain. Generative modeling-based connectome analysis, in particular, plays a vital role in deciphering the neural mechanisms of cognitive functions in health and dysfunction in diseases. Here we review the fo...
Functional connectome "fingerprint" is a cluster of individualized brain functional connectivity patterns that are capable of distinguishing one individual from others. Although its existence has been demonstrated in adolescents and adults, whether such individualized patterns exist since infancy is barely investigated despite its importance in ide...
Major depressive disorder (MDD) represents a grand challenge to human health and society, but the underlying pathophysiological mechanisms remain elusive. Previous neuroimaging studies have suggested that MDD is associated with abnormal interactions and dynamics in two major neural systems including the default mode - salience (DMN-SAL) network and...
Computational neuroimaging has played a central role in characterizing functional abnormalities in major depressive disorder (MDD). However, most of existing non-invasive analysis tools based on functional magnetic resonance imaging (fMRI) are largely descriptive and superficial, thus cannot offer a deep mechanistic understanding of neural circuit...
Major depressive disorder (MDD) is a serious mental illness characterized by dysfunctional connectivity among distributed brain regions. Previous connectome studies based on functional magnetic resonance imaging (fMRI) have focused primarily on undirected functional connectivity and existing directed effective connectivity (EC) studies concerned mo...
Resting-state functional magnetic resonance imaging (rs-fMRI) studies have focused primarily on characterizing functional or effective connectivity of discrete brain regions. A major drawback of this approach is that it does not provide a mechanistic understanding of brain cognitive function or dysfunction at cellular and circuit levels. To overcom...
The infant brain experiences explosive growth in the first few years of life. The developing topology of the functional network mirrors the emergence of complex cognitive functions. However, early development of brain topological properties in infants is still largely unclear due to the dearth of high-quality longitudinal infant functional MRI (fMR...
Multi-modal structural MRI has been widely used for presurgical glioma grading for treatment planning. Despite providing complementary information, a complete set of high-resolution multi-modality data is costly and often impossible to acquire in clinical settings (although T1 MRI is more commonly acquired). To leverage more comprehensive multimoda...
Objective. Rhythmic brain stimulation has emerged as a powerful tool to modulate cognition and to target pathological oscillations related to neurological and psychiatric disorders. However, we lack a systematic understanding of how periodic stimulation interacts with endogenous neural activity as a function of the brain state and target. Approach....
Generative models are computational models designed to generate appropriate values for all of their embedded variables, thereby simulating the response properties of a complex system based on the coordinated interactions of a multitude of physical mechanisms. In systems neuroscience, generative models are generally biophysically based compartmental...
The olfactory bulb transforms not only the information content of the primary sensory representation, but also its underlying coding metric. High-variance, slow-timescale primary odor representations are transformed by bulbar circuitry into secondary representations based on principal neuron spike patterns that are tightly regulated in time. This e...
Spike timing-based representations of sensory information depend on embedded dynamical frameworks within neuronal networks that establish the rules of local computation and interareal communication. Here, we investigated the dynamical properties of olfactory bulb circuitry in mice of both sexes using microelectrode array recordings from slice and i...
The thalamus plays a critical role in the genesis of thalamocortical oscillations, yet the underlying mechanisms remain elusive. To understand whether the isolated thalamus can generate multiple distinct oscillations, we developed a biophysical thalamic model to test the hypothesis that generation of and transition between distinct thalamic oscilla...
Firing patterns of the HTC and RTC model cells in three different ACh/NE modulatory states.
(A) Voltage responses of the HTC model cell. (A1) Voltage responses of the HTC model cell to three levels of current injection (0 pA, 300 pA and 500 pA; 0–2000 ms) in the low ACh/NE modulatory state. Note that HTC cell generates spontaneous low-threshold bur...
Thalamic α oscillations are abolished when gap junctions among TC cells are blocked in the network.
(A) Thalamic network activities with intact gap junctions. (A1) Membrane voltages of two representative HTC, IN, RTC and RE cells each in the control case. (A2) Spike rastergrams of HTC, IN, RTC and RE cells in the control case. (A3) Simulated LFP (t...
Thalamic network activity during the first harmonic entrainment (1:2) of γ oscillations.
(A) Top four panels: spike rastergrams of HTC, IN, RTC and RE cells; bottom panel: stimulation waveform.
(B) Simulated LFP (top) with associated frequency power spectrum (bottom).
(TIF)
Maximal conductance densities (mS/cm2) of active ionic currents in the HTC, RTC, IN and RE model cells.
(DOCX)
Effect of possible NE modulation on INs during alpha oscillations.
(A) Alpha oscillations during the control condition when the NE modulatory effect on INs is neglected (gKL = 0.02 mS/cm2). (A1) Membrane voltages of representative HTC, IN, RTC and RE cells. (A2) Spike rastergrams of HTC, IN, RTC and RE cells. (A3) Simulated LFP (top) with associate...
Effect of possible NE modulation on INs during gamma oscillations.
(A) Gamma oscillations during the control condition when the NE modulatory effect on INs is neglected (gKL = 0.02 mS/cm2). (A1) Membrane voltages of representative HTC, IN, RTC and RE cells. (A2) Spike rastergrams of HTC, IN, RTC and RE cells. (A3) Simulated LFP (top) with associate...
IN neurons become phase-locked to the γ rhythm when the short-term depression (STD) at the HTC→IN synapses is removed.
(A) INs are not phase locked to the γ rhythm in the control case. (A1) Spike rastergrams of HTC, IN, RTC and RE cells. (A2) Distribution of spike phases relative to sLFP peaks for HTC, IN, RTC and RE cells.
(B) INs are phase locked...
HTC cells burst randomly under low ACh/NE modulation (0%) and with moderate level input (5 nS) when gap junctions between HTCs are blocked.
(A) Membrane voltages of two representative HTC, IN, RTC and RE cells each.
(B) Spike rastergrams of HTC, IN, RTC and RE cells.
(TIF)
High frequency stimulation of α oscillations suppresses oscillation power.
(A) Thalamic network activity during α oscillations without stimulation. (A1) Spike rastergrams of HTC, IN, RTC and RE cells (top four panels). (A2) Simulated LFP (top) with associated frequency power spectrum (bottom).
(B) Thalamic network activity during 40 Hz stimulation...
Firing patterns of the IN and RE model cells in three different ACh/NE modulatory states.
(A) Voltage responses of the IN model cell. (A1) Voltage responses of the IN model cell to three levels of current injection (50 pA, 100 pA and 200 pA; 500–1500 ms) in the low ACh/NE modulation state. (A2) As (A1), but in the medium ACh/NE modulation state. (A...
Delta oscillation frequency can be reduced by adjusting the leak/potassium leak current (IL/IKL) and the low-threshold T-type Ca2+ current (ICa/T) in TC cells.
(A) Delta oscillation frequency is reduced to about 3 Hz (controls: 3.7 Hz) when the potassium leak conductance in TC cells slightly increases to 0.037 mS/cm2 (controls: 0.035 mS/cm2). (A1)...
High level of RE synchronization is not required for coherent α oscillations.
(A) Spike rastergrams of HTC, IN, RTC and RE cells when the TC→RE synaptic strength is reduced by 50% (AMPA: from 4 nS to 2 nS; NMDA: from 2 nS to 1 nS) and the random input strength to RE cells increases twofold (from 1.5 nS to 3 nS).
(B) Distribution of spike phase rela...
Effect of increasing the excitatory TC→RE synaptic weight on spindle duration.
(A) Membrane voltages of two representative HTC, IN, RTC and RE cells each in the control condition.
(B) Membrane voltage of two representative HTC, IN, RTC and RE cells each when the excitatory TC→RE synaptic weight increases to 150% of its default value (AMPA: from 4 n...
Spontaneous spindle oscillations under low ACh/NE modulation (0%) and with moderate afferent input (6.5 nS).
(A) Membrane voltages of two representative HTC, IN, RTC and RE cells each.
(B) Spike rastergrams of HTC, IN, RTC and RE cells.
(C) Simulated LFP (top) with associated frequency power spectrum (bottom).
(TIF)
The thalamic network becomes desynchronized under low ACh/NE modulation (0%) when the afferent input is strong (20 nS).
(A) Membrane voltages of two representative HTC, IN, RTC and RE cells each.
(B) Spike rastergrams of HTC, IN, RTC and RE cells.
(TIF)
Firing patterns of single thalamic model neurons.
(DOCX)
Kinetics of gating variables for each channel implemented in the HTC, RTC, IN and RE model cells.
(DOCX)
Effect of possible NE modulation on INs during spindle oscillations.
(A) Spindle oscillations during the control condition when the NE modulatory effect on INs is neglected (gKL = 0.015 mS/cm2). (A1) Membrane voltages of representative HTC, IN, RTC and RE cells. (A2) Spike rastergrams of HTC, IN, RTC and RE cells. (A3) Simulated LFP (top) with asso...
The thalamic network oscillation frequency is reduced to the β band (e.g., 23.2 Hz) when the synaptic input drive to TC cells is reduced (e.g., from 17 nS to 10 nS).
(A) Membrane voltages of two representative HTC, IN, RTC and RE cells each.
(B) Spike rastergrams of HTC, IN, RTC and RE cells.
(C) Simulated LFP (top) with associated frequency power...
Thalamic δ oscillations are altered when specific gap junctions between TC cells are blocked.
(A) Simulated LFP (top) with associated frequency power spectrum (bottom) when the gap junctions among HTC cells are blocked.
(B) As (A), but when both HTC-HTC and HTC-RTC gap junctions are blocked.
(TIF)
The duration of spindle oscillations reduces when the afferent input (to TCs) increases under medium level of ACh/NE modulation (50%).
(A) Membrane voltages of two representative HTC, IN, RTC and RE cells each when gInput = 1.5 nS.
(B) Membrane voltages of two representative HTC, IN, RTC and RE cells each when gInput = 2.0 nS.
(C) Membrane voltages...
Transcranial electric stimulation (tES) applies a weak electric current to the scalp, which causes an electric field that changes brain activity and behavior. Despite the rapidly growing number of studies that report successful modulation of behavior in both healthy participants and patients, little is known about how tES modulates brain activity....
Olfactory bulb granule cells are modulated by both acetylcholine (ACh) and norepinephrine (NE), but the effects of these neuromodulators have not been clearly distinguished. We used detailed biophysical simulations of granule cells, both alone and embedded in a microcircuit with mitral cells, to measure and distinguish the effects of ACh and NE on...
Olfactory bulb (OB) periglomerular (PG) cells are heterogeneous with respect to several features, including morphology, connectivity, patterns of protein expression, and electrophysiological properties. However, these features rarely correlate with one another, suggesting that the differentiating properties of PG cells may arise from multiple indep...
Cholinergic inputs from the basal forebrain regulate multiple olfactory bulb (OB) functions, including odor discrimination, perceptual learning, and short-term memory. Previous studies have shown that nicotinic cholinergic receptor activation sharpens mitral cell chemoreceptive fields, likely via intraglomerular circuitry. Muscarinic cholinergic ac...
Intercalated (ITC) amygdala neurons regulate fear expression by controlling impulse traffic between the input (basolateral amygdala; BLA) and output (central nucleus; Ce) stations of the amygdala for conditioned fear responses. Previously, stimulation of the infralimbic (IL) cortex was found to reduce fear expression and the responsiveness of Ce ne...
The basolateral amygdala plays an important role in the acquisition and expression of both fear conditioning and fear extinction. To understand how a single structure could encode these "opposite" memories, we developed a biophysical network model of the lateral amygdala (LA) neurons during auditory fear conditioning and extinction. Membrane channe...
p>Computational models are being used in a variety of medical applications, including drug discovery research, where genomic and proteomic software tools facilitate modeling complex intracellular pathways. Increasing understanding of brain functioning due to advances in basic neuroscience techniques and imaging modalities has led to the emergence o...
A computational model of the fear circuit was developed to study regulation of fear by amygdala intercalated (ITC) neurons within the amygdala. A new biophysical model of an ITC neuron was developed first to capture its bistable behavior caused by an unusual slowly deinactivating current. An existing lateral amygdala network model was then extended...
We develop a biophysical network model of the lateral amygdala (LA) neurons to investigate the underlying mechanisms for acquisition and extinction of conditioned fear. A Hodgkin-Huxley formalism is used to model two main types of LA neurons: pyramidal cells and GABAergic interneurons, which are connected based on biological evidence. Hebbian type...
The amygdaloid complex located within the medial temporal lobe plays an important role in the acquisition and expression of learned fear associations (Quirk et al. 2003) and contains three main components: the lateral nucleus (LA), the basal nucleus (BLA), and the central nucleus (CE) (Faber and Sah, 2002). The lateral nucleus of the amygdala (LA)...
Serotonin (5-HT) is widely implicated in brain functions and diseases, but the cellular mechanisms underlying 5-HT functions in the brain are not well understood (Zhang and Arsenault, 2005). Recent experiments (Zhang and Arsenault, 2005) have shown that 5-HT substantially increased the slope (gain) of the firing rate current (F-I) curve in layer 5...
The regulation of the G2 /M transition for the mammalian cell cycle has been modeled using 19 states to investigate the G2 checkpoint dynamics in response to oxidative stress. A detailed network model of G2 /M regulation is presented and then a “core” subsystem is extracted from the full network. An existing model of Mitosis control is extended by...
