Magnetic Resonance Imaging and Spectroscopy Section – Publications

@article{Hu:2019aa,
title = {Compulsive drug use is associated with imbalance of orbitofrontal- and prelimbic-striatal circuits in punishment-resistant individuals.},
author = {Yuzheng Hu and Betty Jo Salmeron and Irina N Krasnova and Hong Gu and Hanbing Lu and Antonello Bonci and Jean L Cadet and Elliot A Stein and Yihong Yang},
url = {https://www.ncbi.nlm.nih.gov/pubmed/30988198},
doi = {10.1073/pnas.1819978116},
issn = {1091-6490 (Electronic); 0027-8424 (Linking)},
year = {2019},
date = {2019-04-30},
journal = {Proc Natl Acad Sci U S A},
volume = {116},
number = {18},
pages = {9066--9071},
address = {Neuroimaging Research Branch, National Institute on Drug Abuse, Intramural Research Programs, National Institutes of Health, Baltimore, MD 21224; yihongyang@intra.nida.nih.gov huyuzheng@zju.edu.cn.},
abstract = {Substance use disorders (SUDs) impose severe negative impacts upon individuals, their families, and society. Clinical studies demonstrate that some chronic stimulant users are able to curtail their drug use when faced with adverse consequences while others continue to compulsively use drugs. The mechanisms underlying this dichotomy are poorly understood, which hampers the development of effective individualized treatments of a disorder that currently has no Food and Drug Administration-approved pharmacological treatments. In the present study, using a rat model of methamphetamine self-administration (SA) in the presence of concomitant foot shocks, thought to parallel compulsive drug taking by humans, we found that SA behavior correlated with alterations in the balance between an increased orbitofrontal cortex-dorsomedial striatal "go" circuit and a decreased prelimbic cortex-ventrolateral striatal "stop" circuit. Critically, this correlation was seen only in rats who continued to self-administer at a relatively high rate despite receiving foot shocks of increasing intensity. While the stop circuit functional connectivity became negative after repeated SA in all rats, "shock-resistant" rats showed strengthening of this negative connectivity after shock exposure. In contrast, "shock-sensitive" rats showed a return toward their baseline levels after shock exposure. These results may help guide novel noninvasive brain stimulation therapies aimed at restoring the physiological balance between stop and go circuits in SUDs.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}

@article{Gu:2019aa,
title = {Regional excitation-inhibition balance predicts default-mode network deactivation via functional connectivity.},
author = {Hong Gu and Yuzheng Hu and Xi Chen and Yong He and Yihong Yang},
url = {https://www.ncbi.nlm.nih.gov/pubmed/30359729},
doi = {10.1016/j.neuroimage.2018.10.055},
issn = {1095-9572 (Electronic); 1053-8119 (Linking)},
year = {2019},
date = {2019-01-15},
journal = {Neuroimage},
volume = {185},
pages = {388--397},
address = {Neuroimaging Research Branch, National Institute on Drug Abuse, Intramural Research Programs, National Institutes of Health, Baltimore, MD, 21224, USA.},
abstract = {Deactivation of the default mode network (DMN) is one of the most reliable observations from neuroimaging and has significant implications in development, aging, and various neuropsychiatric disorders. However, the neural mechanism underlying DMN deactivation remains elusive. As the coordination of regional neurochemical substrates and interregional neural interactions are both essential in support of brain functions, a quantitative description of how they impact DMN deactivation may provide new insights into the mechanism. Using an n-back working memory task fMRI and magnetic resonance spectroscopy, we probed the pairwise relationship between task-induced deactivation, interregional functional connectivity and regional excitation-inhibition balance (evaluated by glutamate/GABA ratio) in the posterior cingulate cortex/precuneus (PCC/PCu). Task-induced PCC/PCu deactivation correlated with its excitation-inhibition balance and interregional functional connectivity, where participants with lower glutamate/GABA ratio, stronger intra-DMN connections and stronger antagonistic DMN-SN (salience network)/ECN (executive control network) inter-network connections had greater PCC/PCu deactivation. Mediation analyses revealed that the DMN-SN functional interactions partially mediated the relationship between task-induced deactivation and the excitation-inhibition balance at the PCC/PCu. The triple-relationship discovered in the present study has the potential to bridge DMN-deactivation related findings from various neuroimaging modalities and may provide new insights into the neural mechanism of DMN deactivation. Moreover, this finding may have significant implications for neuropsychiatric disorders related to the DMN dysfunction and suggests an integrated application of pharmacological and neuromodulation-based strategies for rescuing DMN deactivation deficits.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}

@article{Meng:2018aa,
title = {A novel transcranial magnetic stimulator for focal stimulation of rodent brain.},
author = {Qinglei Meng and Li Jing and Jean Paul Badjo and Xiaoming Du and Elliot Hong and Yihong Yang and Hanbing Lu and Fow-Sen Choa},
url = {https://www.ncbi.nlm.nih.gov/pubmed/29534946},
doi = {10.1016/j.brs.2018.02.018},
issn = {1876-4754 (Electronic); 1876-4754 (Linking)},
year = {2018},
date = {2018-06-01},
journal = {Brain Stimul},
volume = {11},
number = {3},
pages = {663--665},
address = {Department of Computer Science and Electrical Engineering, University of Maryland, Baltimore County, MD, United States; Intramural Research Program, National Institute on Drug Abuse (NIDA), National Institutes of Health (NIH), Baltimore, MD, United States.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}

@article{Liang:2018aab,
title = {The Rich-Club Organization in Rat Functional Brain Network to Balance Between Communication Cost and Efficiency.},
author = {Xia Liang and Li-Ming Hsu and Hanbing Lu and Akira Sumiyoshi and Yong He and Yihong Yang},
url = {https://www.ncbi.nlm.nih.gov/pubmed/28108494},
doi = {10.1093/cercor/bhw416},
issn = {1460-2199 (Electronic); 1047-3211 (Linking)},
year = {2018},
date = {2018-03-01},
journal = {Cereb Cortex},
volume = {28},
number = {3},
pages = {924--935},
address = {Neuroimaging Research Branch, National Institute on Drug Abuse, Baltimore, MD 21224, USA.},
abstract = {Network analyses of structural connectivity in the brain have highlighted a set of highly connected hubs that are densely interconnected, forming a "rich-club" substrate in diverse species. Here, we demonstrate the existence of rich-club organization in functional brain networks of rats. Densely interconnected rich-club regions are found to be distributed in multiple brain modules, with the majority located within the putative default mode network. Rich-club members exhibit high wiring cost (as measured by connection distance) and high metabolic running cost (as surrogated by cerebral blood flow), which may have evolved to achieve high network communications to support efficient brain functions. Furthermore, by adopting a forepaw electrical stimulation paradigm, we find that the rich-club organization of the rat functional network remains almost the same as in the resting state, whereas path motif analysis reveals significant differences, suggesting the rat brain reorganizes its topological routes by increasing locally oriented shortcuts but reducing rich-club member-involved paths to conserve metabolic running cost during unimodal stimulation. Together, our results suggest that the neuronal system is organized and dynamically operated in an economic way to balance between cost minimization and topological/functional efficiency.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}

@article{Geng2017,
title = {Salience and default mode network dysregulation in chronic cocaine users predict treatment outcome.},
author = {Xiujuan Geng and Yuzheng Hu and Hong Gu and Betty Jo Salmeron and Bryon Adinoff and Elliot A Stein and Yihong Yang},
url = {https://www.ncbi.nlm.nih.gov/pubmed/28334915},
doi = {10.1093/brain/awx036},
issn = {1460-2156 (Electronic); 0006-8950 (Linking)},
year = {2017},
date = {2017-05-01},
journal = {Brain},
volume = {140},
number = {5},
pages = {1513--1524},
address = {Neuroimaging Research Branch, National Institute on Drug Abuse, Intramural Research Program, National Institutes of Health, Baltimore, MD, USA.},
abstract = {While chronic cocaine use is associated with abnormalities in both brain structure and function within and interactions between regions, previous studies have been limited to interrogating structure and function independently, and the detected neural differences have not been applied to independent samples to assess the clinical relevance of results. We investigated consequences of structural differences on resting-state functional connectivity in cocaine addiction and tested whether resting-state functional connectivity of the identified circuits predict relapse in an independent cohort. Subjects included 64 non-treatment-seeking cocaine users (NTSCUs) and 67 healthy control subjects and an independent treatment-completed cohort (n = 45) of cocaine-dependent individuals scanned at the end of a 30-day residential treatment programme. Differences in cortical thickness and related resting-state functional connectivity between NTSCUs and healthy control subjects were identified. Survival analysis, applying cortical thickness of the identified regions, resting-state functional connectivity of the identified circuits and clinical characteristics to the treatment cohort, was used to predict relapse. Lower cortical thickness in bilateral insula and higher thickness in bilateral temporal pole were found in NTSCUs versus healthy control subjects. Whole brain resting-state functional connectivity analyses with these four different anatomical regions as seeds revealed eight weaker circuits including within the salience network (insula seeds) and between temporal pole and elements of the default mode network in NTSCUs. Applying these circuits and clinical characteristics to the independent cocaine-dependent treatment cohort, functional connectivity between right temporal pole and medial prefrontal cortex, combined with years of education, predicted relapse status at 150 days with 88% accuracy. Deficits in the salience network suggest an impaired ability to process physiologically salient events, while abnormalities in a temporal pole-medial prefrontal cortex circuit might speak to the social-emotional functional alterations in cocaine addiction. The involvement of the temporal pole-medial prefrontal cortex circuit in a model highly predictive of relapse highlights the importance of social-emotional functions in cocaine dependence, and provides a potential underlying neural target for therapeutic interventions, and for identifying those at high risk of relapse.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}

@article{Hsu2016,
title = {Constituents and functional implications of the rat default mode network.},
author = {Li-Ming Hsu and Xia Liang and Hong Gu and Julia K Brynildsen and Jennifer A Stark and Jessica A Ash and Ching-Po Lin and Hanbing Lu and Peter R Rapp and Elliot A Stein and Yihong Yang},
url = {http://www.ncbi.nlm.nih.gov/pubmed/27439860},
doi = {10.1073/pnas.1601485113},
issn = {1091-6490 (Electronic); 0027-8424 (Linking)},
year = {2016},
date = {2016-08-02},
journal = {Proc Natl Acad Sci U S A},
volume = {113},
number = {31},
pages = {E4541-7},
address = {Neuroimaging Research Branch, National Institute on Drug Abuse, Baltimore, MD 21224; Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, Taipei 112, Taiwan;},
abstract = {The default mode network (DMN) has been suggested to support a variety of self-referential functions in humans and has been fractionated into subsystems based on distinct responses to cognitive tasks and functional connectivity architecture. Such subsystems are thought to reflect functional hierarchy and segregation within the network. Because preclinical models can inform translational studies of neuropsychiatric disorders, partitioning of the DMN in nonhuman species, which has previously not been reported, may inform both physiology and pathophysiology of the human DMN. In this study, we sought to identify constituents of the rat DMN using resting-state functional MRI (rs-fMRI) and diffusion tensor imaging. After identifying DMN using a group-level independent-component analysis on the rs-fMRI data, modularity analyses fractionated the DMN into an anterior and a posterior subsystem, which were further segregated into five modules. Diffusion tensor imaging tractography demonstrates a close relationship between fiber density and the functional connectivity between DMN regions, and provides anatomical evidence to support the detected DMN subsystems. Finally, distinct modulation was seen within and between these DMN subcomponents using a neurocognitive aging model. Taken together, these results suggest that, like the human DMN, the rat DMN can be partitioned into several subcomponents that may support distinct functions. These data encourage further investigation into the neurobiological mechanisms of DMN processing in preclinical models of both normal and disease states.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}

@article{Hu2015,
title = {Impaired functional connectivity within and between frontostriatal circuits and its association with compulsive drug use and trait impulsivity in cocaine addiction.},
author = {Yuzheng Hu and Betty Jo Salmeron and Hong Gu and Elliot A Stein and Yihong Yang},
url = {https://www.ncbi.nlm.nih.gov/pubmed/25853901},
doi = {10.1001/jamapsychiatry.2015.1},
issn = {2168-6238 (Electronic); 2168-622X (Linking)},
year = {2015},
date = {2015-06-01},
journal = {JAMA Psychiatry},
volume = {72},
number = {6},
pages = {584--592},
address = {Neuroimaging Research Branch, Intramural Research Program National Institute on Drug Abuse, Baltimore, Maryland.},
abstract = {IMPORTANCE: Converging evidence has long identified both impulsivity and compulsivity as key psychological constructs in drug addiction. Although dysregulated striatal-cortical network interactions have been identified in cocaine addiction, the association between these brain networks and addiction is poorly understood. OBJECTIVES: To test the hypothesis that cocaine addiction is associated with disturbances in striatal-cortical communication as captured by resting-state functional connectivity (rsFC), measured from coherent spontaneous fluctuations in the blood oxygenation level-dependent functional magnetic resonance imaging signal, and to explore the relationships between striatal rsFC, trait impulsivity, and uncontrolled drug use in cocaine addiction. DESIGN, SETTING, AND PARTICIPANTS: A case-control, cross-sectional study was conducted at the National Institute on Drug Abuse Intramural Research Program outpatient magnetic resonance imaging facility. Data used in the present study were collected between December 8, 2005, and September 30, 2011. Participants included 56 non-treatment-seeking cocaine users (CUs) (52 with cocaine dependence and 3 with cocaine abuse) and 56 healthy individuals serving as controls (HCs) matched on age, sex, years of education, race, estimated intelligence, and smoking status. MAIN OUTCOMES AND MEASURES: Voxelwise statistical parametric analysis testing the rsFC strength differences between CUs and HCs in brain regions functionally connected to 6 striatal subregions defined a priori. RESULTS: Increased rsFC strength was observed predominantly in striatal-frontal circuits; decreased rsFC was found between the striatum and cingulate, striatal, temporal, hippocampal/amygdalar, and insular regions in the CU group compared with the HCs. Increased striatal-dorsal lateral prefrontal cortex connectivity strength was positively correlated with the amount of recent cocaine use (uncorrected P < .046) and elevated trait impulsivity in the CUs (uncorrected P < .012), and an index reflecting the balance between striatal-dorsal anterior cingulate cortex and striatal-anterior prefrontal/orbitofrontal cortex circuits was significantly associated with loss of control over cocaine use (corrected P < .012). CONCLUSIONS AND RELEVANCE: Cocaine addiction is associated with disturbed rsFC in several specific striatal-cortical circuits. Specifically, compulsive cocaine use, a defining characteristic of dependence, was associated with a balance of increased striatal-anterior prefrontal/orbitofrontal and decreased striatal-dorsal anterior cingulate connectivity; trait impulsivity, both a risk factor for and a consequence of cocaine use, was associated with increased dorsal striatal-dorsal lateral prefrontal cortex connectivity uniquely in CUs. These findings provide new insights toward the neurobiological mechanisms of addiction and suggest potential novel therapeutic targets for treatment.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}

@article{Liang:2015aa,
title = {Interactions between the salience and default-mode networks are disrupted in cocaine addiction.},
author = {Xia Liang and Yong He and Betty Jo Salmeron and Hong Gu and Elliot A Stein and Yihong Yang},
url = {https://www.ncbi.nlm.nih.gov/pubmed/26019326},
doi = {10.1523/JNEUROSCI.3188-14.2015},
issn = {1529-2401 (Electronic); 0270-6474 (Linking)},
year = {2015},
date = {2015-05-27},
journal = {J Neurosci},
volume = {35},
number = {21},
pages = {8081--8090},
address = {Neuroimaging Research Branch, National Institute on Drug Abuse, National Institutes of Health, Baltimore, Maryland 21224, and State Key Laboratory of Cognitive Neuroscience and Learning & IDG/McGovern Institute for Brain Research, Beijing Normal University, Beijing, China 100875.},
abstract = {Cocaine dependence is a complex neuropsychiatric disorder manifested as dysregulation of multiple behavioral, emotional, and cognitive constructs. Neuroimaging studies have begun to identify specific neurobiological circuit impairments in cocaine-dependent (CD) individuals that may underlie these symptoms. However, whether, where, and how the interactions within and between these circuits are disrupted remain largely unknown. We used resting-state fMRI and modularity network analysis to identify brain modules of a priori interest (default-mode network [DMN], salience network [SN], executive control network [ECN], medial temporal lobe [MTL], and striatum) in 47 CD and 47 matched healthy control (HC) participants and explored alterations within and between these brain modules as a function of addiction. At the module level, intermodule connectivity decreased between DMN and SN in CD. At the nodal level, several regions showed decreased connections with multiple modules in CD: the rostral anterior cingulate connection strength was reduced with SN and MTL; the posterior cingulate had reduced connections with ECN; and the bilateral insula demonstrated decreased connections with DMN. Furthermore, alexithymia, a personality trait previously associated with addiction, correlated negatively with intramodule connectivity within SN only in cocaine users. Our results indicate that cocaine addiction is associated with disrupted interactions among DMN, MTL, and SN, which have been implicated, respectively, in self-referential functions, emotion and memory, and coordinating between internal and external stimuli, providing novel and important insights into the neurobiological mechanisms of cocaine addiction.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}

@article{Liang2015,
title = {Topologically Reorganized Connectivity Architecture of Default-Mode, Executive-Control, and Salience Networks across Working Memory Task Loads.},
author = {Xia Liang and Qihong Zou and Yong He and Yihong Yang},
url = {https://www.ncbi.nlm.nih.gov/pubmed/25596593},
doi = {10.1093/cercor/bhu316},
issn = {1460-2199 (Electronic); 1047-3211 (Linking)},
year = {2015},
date = {2015-01-16},
journal = {Cereb Cortex},
volume = {26},
number = {4},
pages = {1501--1511},
address = {Neuroimaging Research Branch, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD 21224, USA.},
abstract = {The human brain is topologically organized into a set of spatially distributed, functionally specific networks. Of these networks, the default-mode network (DMN), executive-control network (ECN), and salience network (SN) have received the most attention recently for their vital roles in cognitive functions. However, very little is known about whether and how the interactions within and between these 3 networks would be modulated by cognitive demands. Here, we employed graph-based modularity analysis to identify the DMN, ECN, and SN during an N-back working memory (WM) task and further investigated the modulation of intra- and inter-network interactions at different cognitive loads. As the task load elevated, functional connectivity decreased within the DMN while increased within the ECN, and the SN connected more with both the DMN and ECN. Within-network connectivity of the ventral and dorsal posterior cingulate cortex was differentially modulated by cognitive load. Further, the superior parietal regions in the ECN showed increased internetwork connections at higher WM loads, and these increases correlated positively with WM task performance. Together, these findings advance our understanding of dynamic integrations of specialized brain systems in response to cognitive demands and may serve as a baseline for assessing potential disruptions of these interactions in pathological conditions.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}

@article{Lu2014,
title = {Low- but Not High-Frequency LFP Correlates with Spontaneous BOLD Fluctuations in Rat Whisker Barrel Cortex.},
author = {Hanbing Lu and Leiming Wang and William W Rea and Julia K Brynildsen and Saul Jaime and Yantao Zuo and Elliot A Stein and Yihong Yang},
url = {https://www.ncbi.nlm.nih.gov/pubmed/25331598},
doi = {10.1093/cercor/bhu248},
issn = {1460-2199 (Electronic); 1047-3211 (Linking)},
year = {2014},
date = {2014-10-20},
journal = {Cereb Cortex},
volume = {26},
number = {2},
pages = {683--694},
address = {Neuroimaging Research Branch and.},
abstract = {Resting-state magnetic resonance imaging (rsMRI) is thought to reflect ongoing spontaneous brain activity. However, the precise neurophysiological basis of rsMRI signal remains elusive. Converging evidence supports the notion that local field potential (LFP) signal in the high-frequency range correlates with fMRI response evoked by a task (e.g., visual stimulation). It remains uncertain whether this relationship extends to rsMRI. In this study, we systematically modulated LFP signal in the whisker barrel cortex (WBC) by unilateral deflection of rat whiskers. Results show that functional connectivity between bilateral WBC was significantly modulated at the 2 Hz, but not at the 4 or 6 Hz, stimulus condition. Electrophysiologically, only in the low-frequency range (<5 Hz) was the LFP power synchrony in bilateral WBC significantly modulated at 2 Hz, but not at 4- or 6-Hz whisker stimulation, thus distinguishing these 2 experimental conditions, and paralleling the findings in rsMRI. LFP power synchrony in other frequency ranges was modulated in a way that was neither unique to the specific stimulus conditions nor parallel to the fMRI results. Our results support the hypothesis that emphasizes the role of low-frequency LFP signal underlying rsMRI.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}