Transcranial magnetic stimulation (TMS) is one of the most widely used noninvasive brain stimulat... more Transcranial magnetic stimulation (TMS) is one of the most widely used noninvasive brain stimulation method. It has been utilized for both treatment and diagnosis of many neural diseases, such as neuropathic pain and loss of function caused by stroke. Existing TMS tools cannot deliver focused electric field to targeted penetration depth even though many important neurological disorders are originated from there. A breakthrough is needed to achieve noninvasive, focused brain stimulation. We demonstrated using magnetic shield to achieve magnetic focusing without sacrificing significant amount of throughput. The shield is composed of multiple layers of copper ring arrays, which utilize induced current to generate counter magnetic fields. We experimentally set up a two-pole stimulator system to verify device simulation. A transient magnetic field probe was used for field measurements. The focusing effect highly depends on the geometric design of shield. A tight focal spot with a diamete...
We introduce here the concept of a transcranial brain atlas (TBA), a new kind of brain atlas spec... more We introduce here the concept of a transcranial brain atlas (TBA), a new kind of brain atlas specialized for transcranial techniques. A TBA is a probabilistic mapping from scalp space to atlas label space, relating scalp locations to anatomical, functional, network, genetic, or other labels. TBAs offer a new way to integrate and present structural and functional organization of the brain and allow previously subsurface and invisible atlas labels visible on the scalp surface to accurately guide the placement of transcranial devices directly on the scalp surface in a straightforward, visual manner. We present here a framework for building TBAs that includes (i) a new, continuous proportional coordinate system devised for the scalp surface to allow standardized specification of scalp positions; (ii) a high-resolution, large sample-based (114-participant) mapping from scalp space to brain space to accurately and reliably describe human cranio-cortical correspondence; and (iii) a two-step Markov chain to combine the probabilistic scalp-brain mapping with a traditional brain atlas, bringing atlas labels to the scalp surface. We assessed the reproducibility (consistency of TBAs generated from different groups) and predictiveness (prediction accuracy of labels for individuals without brain images) of the TBAs built via our framework. Moreover, we present an application of TBAs to a functional near-infrared spectroscopy finger-tapping experiment, illustrating the utility and benefits of TBAs in transcranial studies. Our results demonstrate that TBAs can support ongoing efforts to map the human brain using transcranial techniques, just as traditional brain atlases have supported magnetic resonance imaging and positron emission tomography studies.
The insula, a cortical region that integrates heterogeneous signals about internal states and con... more The insula, a cortical region that integrates heterogeneous signals about internal states and contributes to executive functions, has been implicated as an important role in the maintenance of nicotine dependence. Previous studies have indicated that insula damage may contribute to quitting smoking successfully, but few studies have examined whether quitting successfully is related to cortical structural integrity of insular subregions before smoking cessation treatment. Moreover, although prior researches have shown group differences in insular cortex structure in chronic cigarette smokers compared to nonsmokers, less is known about how cortical structural integrity of insular subregions relate to smoking behaviors in smokers. This study, therefore, aimed to (1) further explore the association between the cortical structural integrity of insular subregions prior to the target quit date and the treatment outcomes of smoking cessation therapy; and (2) further evaluate how the cortical structural integrity of insular subregions are related to smoking behaviors. In the present study, a total of 83 smokers and 41 nonsmokers were enrolled and high-resolution structural magnetic resonance images were acquired from all participants. After a 12-week smoking cessation treatment, 28 smokers succeeded in quitting smoking, 46 failed, and 9 were unable to be contacted. Our analysis showed that gray-matter volume of bilateral anterior insula were negatively correlated with nicotine dependence scores. However, the smoking cessation outcomes showed no correlations with the gray-matter volume and seed-based structural covariance network of insular subregions prior to smoking cessation. The present study further clarified the more precise roles of the insular cortex in smoking behaviors, which might improve the understanding of the mechanism in the nicotine dependence.
Alzheimer's disease (AD) is characterized by progressive cognitive impairment and by exte... more Alzheimer's disease (AD) is characterized by progressive cognitive impairment and by extensive neuronal loss associated with extracellular amyloid β-peptide (Aβ) plaques and intraneuronal tau pathology in temporal and parietal lobes. AD patients are at increased risk for epileptic seizures, and data from experimental models of AD suggest that aberrant neuronal network activity occurs early in the disease process before cognitive deficits and neuronal degeneration. The contributions of Aβ and/or tau pathologies to dysregulation of neuronal network activity are unclear. Using a transgenic mouse model of AD (3×TgAD mice) in which there occurs differential age-dependent development of tau and Aβ plaque pathologies, we applied analysis of resting state functional magnetic resonance imaging regional homogeneity, a measure of local synchronous activity, to discriminate the effects of Aβ and tau on neuronal network activity throughout the brain. Compared to age-matched wild-type mice, 6- to 8-month-old 3×TgAD mice exhibited increased regional homogeneity in the hippocampus and parietal and temporal cortices, regions with tau pathology but not Aβ pathology at this age. By 18-24 months of age, 3×TgAD mice exhibited extensive tau and Aβ pathologies involving the hippocampus and multiple functionally related brain regions, with a spatial expansion of increased local synchronous activity to include those regions. Our findings demonstrate that age-related brain regional hypersynchronous activity is associated with early tau pathology in a mouse model, consistent with a role for early tau pathology in the neuronal circuit hyperexcitability that is believed to precede and contribute to neuronal degeneration in AD.
Hypnosis has been shown to have treatment effects on nicotine addiction. However, the neural basi... more Hypnosis has been shown to have treatment effects on nicotine addiction. However, the neural basis of these effects is poorly understood. This preliminary study investigated the neural mechanisms of hypnosis-based treatment on cigarette smoking, specifically, whether the hypnosis involves a top-down or bottom-up mechanism. Two groups of 45 smokers underwent a smoking aversion suggestion and viewed smoking-related pictures and neutral pictures. One group underwent functional magnetic resonance imaging scanning twice (control and hypnotic states), whereas the other group underwent two electroencephalograph sessions. Our study found that self-reported smoking craving decreased in both groups following hypnosis. Smoking cue-elicited activations in the right dorsal lateral prefrontal cortex (rDLPFC) and left insula (lI) and the functional connectivity between the rDLPFC and lI were increased in the hypnotic state compared with the control state. The delta band source waveforms indicated ...
The monoamine oxidase A (MAOA) enzyme metabolizes monoamine neurotransmitters such as dopamine, s... more The monoamine oxidase A (MAOA) enzyme metabolizes monoamine neurotransmitters such as dopamine, serotonin and norepinephrine, and its genetic polymorphism (rs1137070) influences its activity level and is associated with smoking behaviors. However, the underlying neural mechanisms of the gene × environment interactions remain largely unknown. In this study, we aimed to explore the interactive effects of the rs1137070 and cigarette smoking on gray matter volume (GMV) and functional connectivity strength (FCS). A total of 81 smokers and 42 nonsmokers were enrolled in the present study. Voxel-based morphometry analysis showed a significant rs1137070 genotype × smoking effect on the GMV of the left orbitofrontal cortex (OFC), such that individuals with risk allele had greater GMV among nonsmokers but not smokers. Meanwhile, rs1137070 variant and nicotine dependence interactively altered the FCS of the right hippocampus, the left inferior parietal lobule (IPL), the left dorsolateral prefrontal cortex and bilateral OFC. In addition, the FCS in the left IPL was correlated with smoking initiation and smoking years in smokers with the risk allele. These findings suggest that MAOA rs1137070 contributes to the susceptibility to nicotine dependence through its influence on brain circuits involved in reward and attention, and interacts with smoking in the progression.
Functional connectivity MRI, based on Blood-Oxygenation-Level-Dependent (BOLD) signals, is typica... more Functional connectivity MRI, based on Blood-Oxygenation-Level-Dependent (BOLD) signals, is typically performed while the subject is at rest. On the other hand, BOLD is also widely used in physiological imaging such as cerebrovascular reactivity (CVR) mapping using hypercapnia (HC) as a modulator. We therefore hypothesize that hypercapnia BOLD data can be used to extract FC metrics after factoring out the effects of the physiological modulation, which will allow simultaneous assessment of neural and vascular function and may be particularly important in populations such as aging and cerebrovascular diseases. The present work aims to systematically examine the feasibility of hypercapnia BOLD-based FC mapping using three commonly applied analysis methods, specifically dual-regression Independent Component Analysis (ICA), region-based FC matrix analysis, and graph-theory based network analysis, in a large cohort of 170 healthy subjects ranging from 20 to 88 years old. To validate the hypercapnia BOLD results, we also compared these FC metrics with those obtained from conventional resting-state data. ICA analysis of the hypercapnia BOLD data revealed FC maps that strongly resembled those reported in the literature. FC matrix using region-based analysis showed a correlation of 0.97 on the group-level and 0.54 ± 0.10 on the individual-level, when comparing between hypercapnia and resting-state results. Although the correspondence on the individual-level was moderate, this was primarily attributed to variations intrinsic to FC mapping, because a corresponding resting-vs-resting comparison in a sub-cohort (N = 39) revealed a similar correlation of 0.57 ± 0.09. Graph-theory computations were also feasible in hypercapnia BOLD data and indices of global efficiency, clustering coefficient, modularity, and segregation were successfully derived. Hypercapnia FC results revealed age-dependent differences in which within-network connections generally exhibited an age-dependent decrease while between-network connections showed an age-dependent increase.
Cerebral cortex (New York, N.Y. : 1991), Jan 28, 2018
Coordinated activity within and differential activity between large-scale neuronal networks such ... more Coordinated activity within and differential activity between large-scale neuronal networks such as the default mode network (DMN) and the control network (CN) is a critical feature of brain organization. The CN usually exhibits activations in response to cognitive tasks while the DMN shows deactivations; in addition, activity between the two networks is anti-correlated at rest. To address this issue, we used functional MRI to measure whole-brain BOLD signal during resting-state and task-evoked conditions, and MR spectroscopy (MRS) to quantify GABA and glutamate concentrations, in nodes within the DMN and CN (MPFC and DLPFC, respectively) in 19 healthy individuals at 3 Tesla. We found that GABA concentrations in the MPFC were significantly associated with DMN deactivation during a working memory task and with anti-correlation between DMN and CN at rest and during task performance, while GABA concentrations in the DLPFC weakly modulated DMN-CN anti-correlation in the opposite directi...
fMRI blood oxygenation level-dependent (BOLD) signal has been widely used as a surrogate for neur... more fMRI blood oxygenation level-dependent (BOLD) signal has been widely used as a surrogate for neural activity. However, interpreting differences in BOLD fMRI based on underlying neuronal activity remains a challenge. Concurrent rsMRI data collection and electrophysiological recording in combination with microiontophoretically injected modulatory chemicals allows for improved understanding of the relationship between resting state BOLD and neuronal activity. Simultaneous fMRI, multi-channel intracortical electrophysiology and focal pharmacological manipulation data to be acquired longitudinally in rats for up to 2 months. Our artifact replacing technique is optimized for combined LFP and rsMRI data collection. Intracortical implantation of a multichannel microelectrode array resulted in minimal distortion and signal loss in fMRI images inside a 9.4T MRI scanner. rsMRI-induced electrophysiology artifacts were replaced using an in-house developed algorithm. Microinjection of AMPA (α-ami...
To date, fractionation of the nicotine addiction phenotype has been limited to that based primari... more To date, fractionation of the nicotine addiction phenotype has been limited to that based primarily on characteristics of cigarette use, although it is widely appreciated that a variety of individual factors are associated with tobacco use disorder. Identifying subtypes of tobacco use disorder based on such factors may lead to better understanding of potential treatment targets, individualize treatments and improve outcomes. In this preliminary study, to identify potential subgroups, we applied hierarchical clustering to a broad range of assessments measuring personality, IQ and psychiatric symptoms, as well as various environmental and experiential characteristics from 102 otherwise healthy cigarette smokers. The identified subgroups were further compared on various resting-state fMRI measures from a subset (N = 65) of individuals who also underwent resting-state fMRI scanning. The clustering dendrogram indicated that smokers can be divided into three subgroups. Each subgroup had u...
Huntington's disease (HD) is an autosomal dominant inherited neurodegenerative disorder, and ... more Huntington's disease (HD) is an autosomal dominant inherited neurodegenerative disorder, and no cure is available currently. Treatment of HD is likely to be most beneficial in the early, possibly pre-manifestation stage. The challenge is to determine the best time for intervention and evaluate putative efficacy in the absence of clinical symptoms. Resting-state functional MRI may represent a promising tool to develop biomarker reflecting early neuronal dysfunction in HD brain, because it can examine multiple brain networks without confounding effects of cognitive ability, which makes the resting-state fMRI promising as a translational bridge between preclinical study in animal models and clinical findings in HD patients. In this study, we examined brain regional connectivity and its correlation to brain atrophy, as well as motor function in the 18-week-old N171-82Q HD mice. HD mice exhibited significantly altered functional connectivity in multiple networks. Particularly, the we...
Tobacco use disorder is frequently comorbid with emotional disorders, each exerting reciprocal in... more Tobacco use disorder is frequently comorbid with emotional disorders, each exerting reciprocal influence on the other. As an important hub for emotional processing, amygdala may also play a critical role in tobacco addiction. Therefore, we aimed to investigate the volume and spontaneous activity of the amygdala in nicotine-dependent individuals and their relationships with cigarette use. A total of 84 smokers (aged 22-54 years) and 41 nonsmokers (aged 26-56 years) were enrolled in the present study. 3D-T1 weighted images and resting-state fMRI images were acquired from all participants. We used ROI-wise volume, fractional amplitude of low frequency fluctuation (fALFF) and resting-state functional connectivity (FC) to assess structural and functional changes of the amygdala in the smokers. There was no significant difference between smokers and nonsmokers on amygdala volume (p > 0.05). When compared to nonsmokers, increased fALFF in the right amygdala was observed in smokers (p = ...
Similarities on the cellular and neurochemical composition of the amygdaloid subnuclei suggests t... more Similarities on the cellular and neurochemical composition of the amygdaloid subnuclei suggests their clustering into subunits that exhibit unique functional organization. The topological principle of community structure has been used to identify functional subnetworks in neuroimaging data that reflect the brain effective organization. Here we used modularity to investigate the organization of the amygdala using resting state functional magnetic resonance imaging (rsfMRI) data. Our goal was to determine whether such topological organization would reliably reflect the known neurobiology of individual amygdaloid nuclei, allowing for human imaging studies to accurately reflect the underlying neurobiology. Modularity analysis identified amygdaloid elements consistent with the main anatomical subdivisions of the amygdala that embody distinct functional and structural properties. Additionally, functional connectivity pathways of these subunits and their correlation with task-induced amygd...
Cerebral cortex (New York, N.Y. : 1991), Jan 17, 2017
Spontaneous ongoing neuronal activity is a prominent feature of the mammalian brain. Temporal and... more Spontaneous ongoing neuronal activity is a prominent feature of the mammalian brain. Temporal and spatial patterns of such ongoing activity have been exploited to examine large-scale brain network organization and function. However, the neurophysiological basis of this spontaneous brain activity as detected by resting-state functional Magnetic Resonance Imaging (fMRI) remains poorly understood. To this end, multi-site local field potentials (LFP) and blood oxygenation level-dependent (BOLD) fMRI were simultaneously recorded in the rat striatum along with local pharmacological manipulation of striatal activity. Results demonstrate that delta (δ) band LFP power negatively, while beta (β) and gamma (γ) band LFPs positively correlated with BOLD fluctuation. Furthermore, there was strong cross-frequency phase-amplitude coupling (PAC), with the phase of δ LFPs significantly modulating the amplitude of the high frequency signal. Enhancing dopaminergic neuronal activity significantly reduce...
In this paper we evaluate the three main methods for correcting the susceptibility-induced artefa... more In this paper we evaluate the three main methods for correcting the susceptibility-induced artefact in diffusion-weighted magnetic-resonance (DW-MR) data, and assess how correction is affected by the susceptibility field's interaction with motion. The susceptibility artefact adversely impacts analysis performed on the data and is typically corrected in post-processing. Correction strategies involve either registration to a structural image, the application of an acquired field-map or the use of additional images acquired with different phase-encoding. Unfortunately, the choice of which method to use is made difficult by the absence of any systematic comparisons of them. In this work we quantitatively evaluate these methods, by extending and employing a recently proposed framework that allows for the simulation of realistic DW-MR datasets with artefacts. Our analysis separately evaluates the ability for methods to correct for geometric distortions and to recover lost information ...
Nicotine dependence (ND) is a chronic, relapsing mental disorder characterized by compulsive ciga... more Nicotine dependence (ND) is a chronic, relapsing mental disorder characterized by compulsive cigarette seeking and smoking. Although the cerebellum plays an increasingly implicated role in ND, the exact cerebellar alterations in ND remain unclear. Identifying the localization of these cerebellar abnormalities in ND may help to further understand the role of the cerebellum in ND. Thus, we investigated the structural and functional alterations in the cerebellum in a large sample of smokers using the spatially unbiased infratentorial template (SUIT). High-resolution structural MRI data were acquired from 85 smokers and 41 non-smokers. We applied voxel-based morphometry (VBM) and the SUIT cerebellar atlas to compare the cerebellar gray matter (GM) volume between smokers and non-smokers. Using resting-state fMRI data, we also performed seed-based functional connectivity (FC) analysis to examine the functional correlates of the GM volume changes. Both VBM and lobular analyses revealed smaller GM volume in the bilateral Crus I in smokers. The GM volume of the left Crus I was inversely correlated with the severity of nicotine dependence as assessed by Fagerström Test for Nicotine Dependence (FTND) (r=-0.268, p=0.013). We also found reduced FC between the bilateral Crus I and brain regions involved in the default mode network (DMN) and motor system, as well as the frontal and temporal cortex in smokers. Our results indicate that decreased cerebellar GM volume and cortico-cerebellar FC are associated with ND, and these may underlie the core ND phenotypes, including automatized smoking behavior, cognitive and emotional deficits. As smoking remains a worldwide public health problem, identifying the related neural alterations may help to understand the pathophysiology of ND. Based on previous findings in the cerebellum, we investigated the localization of the GM differences and related FC changes in ND subjects. Our findings highlight altered cortico-cerebellar circuits in ND, suggesting an association between the cerebellum and the phenotypes of ND.
Transcranial magnetic stimulation (TMS) is one of the most widely used noninvasive brain stimulat... more Transcranial magnetic stimulation (TMS) is one of the most widely used noninvasive brain stimulation method. It has been utilized for both treatment and diagnosis of many neural diseases, such as neuropathic pain and loss of function caused by stroke. Existing TMS tools cannot deliver focused electric field to targeted penetration depth even though many important neurological disorders are originated from there. A breakthrough is needed to achieve noninvasive, focused brain stimulation. We demonstrated using magnetic shield to achieve magnetic focusing without sacrificing significant amount of throughput. The shield is composed of multiple layers of copper ring arrays, which utilize induced current to generate counter magnetic fields. We experimentally set up a two-pole stimulator system to verify device simulation. A transient magnetic field probe was used for field measurements. The focusing effect highly depends on the geometric design of shield. A tight focal spot with a diamete...
We introduce here the concept of a transcranial brain atlas (TBA), a new kind of brain atlas spec... more We introduce here the concept of a transcranial brain atlas (TBA), a new kind of brain atlas specialized for transcranial techniques. A TBA is a probabilistic mapping from scalp space to atlas label space, relating scalp locations to anatomical, functional, network, genetic, or other labels. TBAs offer a new way to integrate and present structural and functional organization of the brain and allow previously subsurface and invisible atlas labels visible on the scalp surface to accurately guide the placement of transcranial devices directly on the scalp surface in a straightforward, visual manner. We present here a framework for building TBAs that includes (i) a new, continuous proportional coordinate system devised for the scalp surface to allow standardized specification of scalp positions; (ii) a high-resolution, large sample-based (114-participant) mapping from scalp space to brain space to accurately and reliably describe human cranio-cortical correspondence; and (iii) a two-step Markov chain to combine the probabilistic scalp-brain mapping with a traditional brain atlas, bringing atlas labels to the scalp surface. We assessed the reproducibility (consistency of TBAs generated from different groups) and predictiveness (prediction accuracy of labels for individuals without brain images) of the TBAs built via our framework. Moreover, we present an application of TBAs to a functional near-infrared spectroscopy finger-tapping experiment, illustrating the utility and benefits of TBAs in transcranial studies. Our results demonstrate that TBAs can support ongoing efforts to map the human brain using transcranial techniques, just as traditional brain atlases have supported magnetic resonance imaging and positron emission tomography studies.
The insula, a cortical region that integrates heterogeneous signals about internal states and con... more The insula, a cortical region that integrates heterogeneous signals about internal states and contributes to executive functions, has been implicated as an important role in the maintenance of nicotine dependence. Previous studies have indicated that insula damage may contribute to quitting smoking successfully, but few studies have examined whether quitting successfully is related to cortical structural integrity of insular subregions before smoking cessation treatment. Moreover, although prior researches have shown group differences in insular cortex structure in chronic cigarette smokers compared to nonsmokers, less is known about how cortical structural integrity of insular subregions relate to smoking behaviors in smokers. This study, therefore, aimed to (1) further explore the association between the cortical structural integrity of insular subregions prior to the target quit date and the treatment outcomes of smoking cessation therapy; and (2) further evaluate how the cortical structural integrity of insular subregions are related to smoking behaviors. In the present study, a total of 83 smokers and 41 nonsmokers were enrolled and high-resolution structural magnetic resonance images were acquired from all participants. After a 12-week smoking cessation treatment, 28 smokers succeeded in quitting smoking, 46 failed, and 9 were unable to be contacted. Our analysis showed that gray-matter volume of bilateral anterior insula were negatively correlated with nicotine dependence scores. However, the smoking cessation outcomes showed no correlations with the gray-matter volume and seed-based structural covariance network of insular subregions prior to smoking cessation. The present study further clarified the more precise roles of the insular cortex in smoking behaviors, which might improve the understanding of the mechanism in the nicotine dependence.
Alzheimer's disease (AD) is characterized by progressive cognitive impairment and by exte... more Alzheimer's disease (AD) is characterized by progressive cognitive impairment and by extensive neuronal loss associated with extracellular amyloid β-peptide (Aβ) plaques and intraneuronal tau pathology in temporal and parietal lobes. AD patients are at increased risk for epileptic seizures, and data from experimental models of AD suggest that aberrant neuronal network activity occurs early in the disease process before cognitive deficits and neuronal degeneration. The contributions of Aβ and/or tau pathologies to dysregulation of neuronal network activity are unclear. Using a transgenic mouse model of AD (3×TgAD mice) in which there occurs differential age-dependent development of tau and Aβ plaque pathologies, we applied analysis of resting state functional magnetic resonance imaging regional homogeneity, a measure of local synchronous activity, to discriminate the effects of Aβ and tau on neuronal network activity throughout the brain. Compared to age-matched wild-type mice, 6- to 8-month-old 3×TgAD mice exhibited increased regional homogeneity in the hippocampus and parietal and temporal cortices, regions with tau pathology but not Aβ pathology at this age. By 18-24 months of age, 3×TgAD mice exhibited extensive tau and Aβ pathologies involving the hippocampus and multiple functionally related brain regions, with a spatial expansion of increased local synchronous activity to include those regions. Our findings demonstrate that age-related brain regional hypersynchronous activity is associated with early tau pathology in a mouse model, consistent with a role for early tau pathology in the neuronal circuit hyperexcitability that is believed to precede and contribute to neuronal degeneration in AD.
Hypnosis has been shown to have treatment effects on nicotine addiction. However, the neural basi... more Hypnosis has been shown to have treatment effects on nicotine addiction. However, the neural basis of these effects is poorly understood. This preliminary study investigated the neural mechanisms of hypnosis-based treatment on cigarette smoking, specifically, whether the hypnosis involves a top-down or bottom-up mechanism. Two groups of 45 smokers underwent a smoking aversion suggestion and viewed smoking-related pictures and neutral pictures. One group underwent functional magnetic resonance imaging scanning twice (control and hypnotic states), whereas the other group underwent two electroencephalograph sessions. Our study found that self-reported smoking craving decreased in both groups following hypnosis. Smoking cue-elicited activations in the right dorsal lateral prefrontal cortex (rDLPFC) and left insula (lI) and the functional connectivity between the rDLPFC and lI were increased in the hypnotic state compared with the control state. The delta band source waveforms indicated ...
The monoamine oxidase A (MAOA) enzyme metabolizes monoamine neurotransmitters such as dopamine, s... more The monoamine oxidase A (MAOA) enzyme metabolizes monoamine neurotransmitters such as dopamine, serotonin and norepinephrine, and its genetic polymorphism (rs1137070) influences its activity level and is associated with smoking behaviors. However, the underlying neural mechanisms of the gene × environment interactions remain largely unknown. In this study, we aimed to explore the interactive effects of the rs1137070 and cigarette smoking on gray matter volume (GMV) and functional connectivity strength (FCS). A total of 81 smokers and 42 nonsmokers were enrolled in the present study. Voxel-based morphometry analysis showed a significant rs1137070 genotype × smoking effect on the GMV of the left orbitofrontal cortex (OFC), such that individuals with risk allele had greater GMV among nonsmokers but not smokers. Meanwhile, rs1137070 variant and nicotine dependence interactively altered the FCS of the right hippocampus, the left inferior parietal lobule (IPL), the left dorsolateral prefrontal cortex and bilateral OFC. In addition, the FCS in the left IPL was correlated with smoking initiation and smoking years in smokers with the risk allele. These findings suggest that MAOA rs1137070 contributes to the susceptibility to nicotine dependence through its influence on brain circuits involved in reward and attention, and interacts with smoking in the progression.
Functional connectivity MRI, based on Blood-Oxygenation-Level-Dependent (BOLD) signals, is typica... more Functional connectivity MRI, based on Blood-Oxygenation-Level-Dependent (BOLD) signals, is typically performed while the subject is at rest. On the other hand, BOLD is also widely used in physiological imaging such as cerebrovascular reactivity (CVR) mapping using hypercapnia (HC) as a modulator. We therefore hypothesize that hypercapnia BOLD data can be used to extract FC metrics after factoring out the effects of the physiological modulation, which will allow simultaneous assessment of neural and vascular function and may be particularly important in populations such as aging and cerebrovascular diseases. The present work aims to systematically examine the feasibility of hypercapnia BOLD-based FC mapping using three commonly applied analysis methods, specifically dual-regression Independent Component Analysis (ICA), region-based FC matrix analysis, and graph-theory based network analysis, in a large cohort of 170 healthy subjects ranging from 20 to 88 years old. To validate the hypercapnia BOLD results, we also compared these FC metrics with those obtained from conventional resting-state data. ICA analysis of the hypercapnia BOLD data revealed FC maps that strongly resembled those reported in the literature. FC matrix using region-based analysis showed a correlation of 0.97 on the group-level and 0.54 ± 0.10 on the individual-level, when comparing between hypercapnia and resting-state results. Although the correspondence on the individual-level was moderate, this was primarily attributed to variations intrinsic to FC mapping, because a corresponding resting-vs-resting comparison in a sub-cohort (N = 39) revealed a similar correlation of 0.57 ± 0.09. Graph-theory computations were also feasible in hypercapnia BOLD data and indices of global efficiency, clustering coefficient, modularity, and segregation were successfully derived. Hypercapnia FC results revealed age-dependent differences in which within-network connections generally exhibited an age-dependent decrease while between-network connections showed an age-dependent increase.
Cerebral cortex (New York, N.Y. : 1991), Jan 28, 2018
Coordinated activity within and differential activity between large-scale neuronal networks such ... more Coordinated activity within and differential activity between large-scale neuronal networks such as the default mode network (DMN) and the control network (CN) is a critical feature of brain organization. The CN usually exhibits activations in response to cognitive tasks while the DMN shows deactivations; in addition, activity between the two networks is anti-correlated at rest. To address this issue, we used functional MRI to measure whole-brain BOLD signal during resting-state and task-evoked conditions, and MR spectroscopy (MRS) to quantify GABA and glutamate concentrations, in nodes within the DMN and CN (MPFC and DLPFC, respectively) in 19 healthy individuals at 3 Tesla. We found that GABA concentrations in the MPFC were significantly associated with DMN deactivation during a working memory task and with anti-correlation between DMN and CN at rest and during task performance, while GABA concentrations in the DLPFC weakly modulated DMN-CN anti-correlation in the opposite directi...
fMRI blood oxygenation level-dependent (BOLD) signal has been widely used as a surrogate for neur... more fMRI blood oxygenation level-dependent (BOLD) signal has been widely used as a surrogate for neural activity. However, interpreting differences in BOLD fMRI based on underlying neuronal activity remains a challenge. Concurrent rsMRI data collection and electrophysiological recording in combination with microiontophoretically injected modulatory chemicals allows for improved understanding of the relationship between resting state BOLD and neuronal activity. Simultaneous fMRI, multi-channel intracortical electrophysiology and focal pharmacological manipulation data to be acquired longitudinally in rats for up to 2 months. Our artifact replacing technique is optimized for combined LFP and rsMRI data collection. Intracortical implantation of a multichannel microelectrode array resulted in minimal distortion and signal loss in fMRI images inside a 9.4T MRI scanner. rsMRI-induced electrophysiology artifacts were replaced using an in-house developed algorithm. Microinjection of AMPA (α-ami...
To date, fractionation of the nicotine addiction phenotype has been limited to that based primari... more To date, fractionation of the nicotine addiction phenotype has been limited to that based primarily on characteristics of cigarette use, although it is widely appreciated that a variety of individual factors are associated with tobacco use disorder. Identifying subtypes of tobacco use disorder based on such factors may lead to better understanding of potential treatment targets, individualize treatments and improve outcomes. In this preliminary study, to identify potential subgroups, we applied hierarchical clustering to a broad range of assessments measuring personality, IQ and psychiatric symptoms, as well as various environmental and experiential characteristics from 102 otherwise healthy cigarette smokers. The identified subgroups were further compared on various resting-state fMRI measures from a subset (N = 65) of individuals who also underwent resting-state fMRI scanning. The clustering dendrogram indicated that smokers can be divided into three subgroups. Each subgroup had u...
Huntington's disease (HD) is an autosomal dominant inherited neurodegenerative disorder, and ... more Huntington's disease (HD) is an autosomal dominant inherited neurodegenerative disorder, and no cure is available currently. Treatment of HD is likely to be most beneficial in the early, possibly pre-manifestation stage. The challenge is to determine the best time for intervention and evaluate putative efficacy in the absence of clinical symptoms. Resting-state functional MRI may represent a promising tool to develop biomarker reflecting early neuronal dysfunction in HD brain, because it can examine multiple brain networks without confounding effects of cognitive ability, which makes the resting-state fMRI promising as a translational bridge between preclinical study in animal models and clinical findings in HD patients. In this study, we examined brain regional connectivity and its correlation to brain atrophy, as well as motor function in the 18-week-old N171-82Q HD mice. HD mice exhibited significantly altered functional connectivity in multiple networks. Particularly, the we...
Tobacco use disorder is frequently comorbid with emotional disorders, each exerting reciprocal in... more Tobacco use disorder is frequently comorbid with emotional disorders, each exerting reciprocal influence on the other. As an important hub for emotional processing, amygdala may also play a critical role in tobacco addiction. Therefore, we aimed to investigate the volume and spontaneous activity of the amygdala in nicotine-dependent individuals and their relationships with cigarette use. A total of 84 smokers (aged 22-54 years) and 41 nonsmokers (aged 26-56 years) were enrolled in the present study. 3D-T1 weighted images and resting-state fMRI images were acquired from all participants. We used ROI-wise volume, fractional amplitude of low frequency fluctuation (fALFF) and resting-state functional connectivity (FC) to assess structural and functional changes of the amygdala in the smokers. There was no significant difference between smokers and nonsmokers on amygdala volume (p > 0.05). When compared to nonsmokers, increased fALFF in the right amygdala was observed in smokers (p = ...
Similarities on the cellular and neurochemical composition of the amygdaloid subnuclei suggests t... more Similarities on the cellular and neurochemical composition of the amygdaloid subnuclei suggests their clustering into subunits that exhibit unique functional organization. The topological principle of community structure has been used to identify functional subnetworks in neuroimaging data that reflect the brain effective organization. Here we used modularity to investigate the organization of the amygdala using resting state functional magnetic resonance imaging (rsfMRI) data. Our goal was to determine whether such topological organization would reliably reflect the known neurobiology of individual amygdaloid nuclei, allowing for human imaging studies to accurately reflect the underlying neurobiology. Modularity analysis identified amygdaloid elements consistent with the main anatomical subdivisions of the amygdala that embody distinct functional and structural properties. Additionally, functional connectivity pathways of these subunits and their correlation with task-induced amygd...
Cerebral cortex (New York, N.Y. : 1991), Jan 17, 2017
Spontaneous ongoing neuronal activity is a prominent feature of the mammalian brain. Temporal and... more Spontaneous ongoing neuronal activity is a prominent feature of the mammalian brain. Temporal and spatial patterns of such ongoing activity have been exploited to examine large-scale brain network organization and function. However, the neurophysiological basis of this spontaneous brain activity as detected by resting-state functional Magnetic Resonance Imaging (fMRI) remains poorly understood. To this end, multi-site local field potentials (LFP) and blood oxygenation level-dependent (BOLD) fMRI were simultaneously recorded in the rat striatum along with local pharmacological manipulation of striatal activity. Results demonstrate that delta (δ) band LFP power negatively, while beta (β) and gamma (γ) band LFPs positively correlated with BOLD fluctuation. Furthermore, there was strong cross-frequency phase-amplitude coupling (PAC), with the phase of δ LFPs significantly modulating the amplitude of the high frequency signal. Enhancing dopaminergic neuronal activity significantly reduce...
In this paper we evaluate the three main methods for correcting the susceptibility-induced artefa... more In this paper we evaluate the three main methods for correcting the susceptibility-induced artefact in diffusion-weighted magnetic-resonance (DW-MR) data, and assess how correction is affected by the susceptibility field's interaction with motion. The susceptibility artefact adversely impacts analysis performed on the data and is typically corrected in post-processing. Correction strategies involve either registration to a structural image, the application of an acquired field-map or the use of additional images acquired with different phase-encoding. Unfortunately, the choice of which method to use is made difficult by the absence of any systematic comparisons of them. In this work we quantitatively evaluate these methods, by extending and employing a recently proposed framework that allows for the simulation of realistic DW-MR datasets with artefacts. Our analysis separately evaluates the ability for methods to correct for geometric distortions and to recover lost information ...
Nicotine dependence (ND) is a chronic, relapsing mental disorder characterized by compulsive ciga... more Nicotine dependence (ND) is a chronic, relapsing mental disorder characterized by compulsive cigarette seeking and smoking. Although the cerebellum plays an increasingly implicated role in ND, the exact cerebellar alterations in ND remain unclear. Identifying the localization of these cerebellar abnormalities in ND may help to further understand the role of the cerebellum in ND. Thus, we investigated the structural and functional alterations in the cerebellum in a large sample of smokers using the spatially unbiased infratentorial template (SUIT). High-resolution structural MRI data were acquired from 85 smokers and 41 non-smokers. We applied voxel-based morphometry (VBM) and the SUIT cerebellar atlas to compare the cerebellar gray matter (GM) volume between smokers and non-smokers. Using resting-state fMRI data, we also performed seed-based functional connectivity (FC) analysis to examine the functional correlates of the GM volume changes. Both VBM and lobular analyses revealed smaller GM volume in the bilateral Crus I in smokers. The GM volume of the left Crus I was inversely correlated with the severity of nicotine dependence as assessed by Fagerström Test for Nicotine Dependence (FTND) (r=-0.268, p=0.013). We also found reduced FC between the bilateral Crus I and brain regions involved in the default mode network (DMN) and motor system, as well as the frontal and temporal cortex in smokers. Our results indicate that decreased cerebellar GM volume and cortico-cerebellar FC are associated with ND, and these may underlie the core ND phenotypes, including automatized smoking behavior, cognitive and emotional deficits. As smoking remains a worldwide public health problem, identifying the related neural alterations may help to understand the pathophysiology of ND. Based on previous findings in the cerebellum, we investigated the localization of the GM differences and related FC changes in ND subjects. Our findings highlight altered cortico-cerebellar circuits in ND, suggesting an association between the cerebellum and the phenotypes of ND.
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