Browsing by Author "Long, Zaiyang"

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    COMPARISON OF BRAIN METABOLITE CHANGES IN MANGANESE-EXPOSED WELDERS AND SMELTERS
    (Office of the Vice Chancellor for Research, 2012-04-13) Long, Zaiyang; Jiang, Yueming; Li, Xiangrong; Xu, Jun; Long, Liling; Zheng, Wei; Murdoch, James; Dydak, Ulrike
    Excessive manganese (Mn) exposure is known to cause cognitive, psychiatric and motor deficits. Mn overexposure occurs in different occupational settings, where the type and level of exposure may vary. Magnetic resonance imaging (MRI) and spectroscopy (MRS) can be used to evaluate brain Mn accumulation and to measure Mn-induced metabolite changes non-invasively. The aim of this study was to compare metabolite changes among different brain regions of welders and smelters following occupational Mn exposure. Nine Mn-exposed smelters, 14 Mn-exposed welders and 23 male matched controls were recruited from a cohort of workers from two factories in China (mean airborne Mn level: 0.227 and 0.025 mg/m3 for smelters and welders, respectively). Short-echo-time 1H MRS spectra were acquired in each subject from four volumes of interest: the frontal cortex, posterior cingulate cortex, hippocampus, and thalamus. We found that 1) in the frontal cortex, significantly decreased creatine (Cr), glutamate (Glu) and glutathione (GSH) were found in welders, whereas decreased Glu was found in smelters as compared to controls. 2) In the thalamus, reduced myo-inositol was found in both smelters and welders, while Glu and GSH were decreased in welders. These results suggest that Mn-induced brain metabolite changes may be regional in nature and more extensive in welders than in smelters. The frontal cortex seems to show a more profound change than the other brain areas tested among Mn exposed subjects. Further studies are needed to investigate the effects of exposure type and length on the mechanism of Mn neurotoxicity. (Supported by NIH/NIEHS R21 ES-017498, National Science Foundation of China Grant #81072320 and 30760210).
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    Decreased GABA levels in anterior cingulate cortex/medial prefrontal cortex in panic disorder
    (Elsevier, 2013) Long, Zaiyang; Medlock, Carla; Dzemidzic, Mario; Shin, Yong-Wook; Goddard, Andrew W.; Dydak, Ulrike; Radiology and Imaging Sciences, School of Medicine
    Changes of various brain metabolites including γ-aminobutyric acid (GABA), measured by 1H-magnetic resonance spectroscopy (MRS), have been reported in panic disorder (PD). Deficits in GABA have been implicated in the pathophysiology of PD. Furthermore, it has been suggested that cortical metabolite changes in PD are familial. Eleven PD patients, including five with and six without a PD family history, and eight age- and gender-matched healthy controls without a family history of psychopathology were recruited. Each subject underwent MRS exams and behavioral assessments (resting visual analog anxiety level and the Panic Disorder Severity Scale). GABA was detected with a MEGA-PRESS J-editing sequence and fitted to minimize macromolecule contaminations. A significant decrease in GABA, expressed as the ratio of GABA over total creatine (GABA/tCr), was detected in the anterior cingulate cortex (ACC)/medial prefrontal cortex (mPFC) in PD patients (p<0.05), which tends to be pronounced in patients with a PD family history. No other patient/control differences in metabolites were noted in the ACC/mPFC or occipital cortex (OCC). Overall, our results indicate that deficits in GABA levels in PD patients vary by brain regions and possibly by family history status.
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    Increased resting-state functional connectivity between the anterior cingulate cortex and the precuneus in panic disorder: resting-state connectivity in panic disorder
    (Elsevier, 2013) Shin, Yong-Wook; Dzemidzic, Mario; Jo, Hang Joon; Long, Zaiyang; Medlock, Carla; Dydak, Ulrike; Goddard, Andrew W.; Radiology and Imaging Sciences, School of Medicine
    Background: The structural and functional abnormalities of the anterior cingulate cortex (ACC) have been reported in panic disorder (PD). Patients with PD have shown decreased gamma-aminobutyric acid (GABA) concentration in the ACC. The GABA concentration in the ACC was found to be associated with default mode network (DMN) activity in normal human subjects. Therefore, it was hypothesized that the DMN would show abnormal activity in PD. Methods: We identified and compared the functional connectivity maps with seed region of interest (ROI) located in the perigenual area of ACC between the 11 patients with panic disorder and age- and sex-matched normal control subjects. Combining magnetic resonance spectroscopy (MRS) and resting fMRI, we investigated the correlation between the GABA concentration in the seed ROI and the index of functional connectivity between ACC and the area showing group differences. Results: The patients with PD showed increased functional connectivity between ACC and precuneus compared to control subjects. The functional connectivity between the ACC and the precuneus negatively correlated with the GABA concentration of the ACC. Limitations: The relatively small sample size and seed based analysis with the selection of a single ROI limits the generalizability of the result. Conclusions: Increased functional connectivity in the two medial nodes of the resting-state default mode network, the ACC and the precuneus, might play an important role in the pathophysiology of panic disorder. The treatment aimed to normalize the functional connectivity between ACC and precuneus might have clinical benefits in PD.
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    Neuroimaging Studies of Essential Tremor: How Well Do These Studies Support/Refute the Neurodegenerative Hypothesis?
    (Ubiquity Press, 2014-05-28) Louis, Elan D.; Huang, Chaorui C.; Dyke, Jonathan P.; Long, Zaiyang; Dydak, Ulrike; Radiology and Imaging Sciences, School of Medicine
    Background: Tissue-based research has recently led to a new patho-mechanistic model of essential tremor (ET)-the cerebellar degenerative model. We are not aware of a study that has reviewed the current neuroimaging evidence, focusing on whether the studies support or refute the neurodegenerative hypothesis of ET. This was our aim. Methods: References for this review were identified by searches of PubMed (1966 to February 2014). Results: Several neuroimaging methods have been used to study ET, most of them based on magnetic resonance imaging (MRI). The methods most specific to address the question of neurodegeneration are MRI-based volumetry, magnetic resonance spectroscopy, and diffusion-weighted imaging. Studies using each of these methods provide support for the presence of cerebellar degeneration in ET, finding reduced cerebellar brain volumes, consistent decreases in cerebellar N-acetylaspartate, and increased mean diffusivity. Other neuroimaging techniques, such as functional MRI and positron emission tomography (PET) are less specific, but still sensitive to potential neurodegeneration. These techniques are used for measuring a variety of brain functions and their impairment. Studies using these modalities also largely support cerebellar neuronal impairment. In particular, changes in (11)C-flumazenil binding in PET studies and changes in iron deposition in an MRI study provide evidence along these lines. The composite data point to neuronal impairment and likely neuronal degeneration in ET. Discussion: Recent years have seen a marked increase in the number of imaging studies of ET. As a whole, the combined data provide support for the presence of cerebellar neuronal degeneration in this disease.
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    Reproducibility and effect of tissue composition on cerebellar GABA MRS in an elderly population.
    (Wiley, 2015-10) Long, Zaiyang; Dyke, Jonathan P.; Ma, Ruoyun; Huang, Chaorui C.; Louis, Elan D.; Dydak, Ulrike; Department of Radiology and Imaging Sciences, IU School of Medicine
    Magnetic resonance spectroscopy (MRS) provides a valuable tool to non-invasively detect brain gamma-amino butyric acid (GABA) in vivo. GABAergic dysfunction has been observed in the aging cerebellum. Studying cerebellar GABA changes is of considerable interest in understanding certain age-related motor disorders. However, little is known about the reproducibility of GABA MRS in an aged population. Therefore, this study aimed to explore the feasibility and reproducibility of GABA MRS in the aged cerebellum at 3.0 Tesla and to examine the effect of differing tissue composition on GABA measurements. MRI and 1H MRS exams were performed on 10 healthy elderly volunteers (mean age 75.2 years ± 6.5 years) using a 3.0 Tesla Siemens Tim Trio scanner. Among them, 5 subjects were scanned twice to assess short-term reproducibility. The MEGA-PRESS J-editing sequence was used for GABA detection in two volumes of interest (VOIs) in left and right cerebellar dentate. MRS data processing and quantification were performed with LCModel 6.3-0L using two separate basis sets, generated from density matrix simulations using published values for chemical shifts and
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    Thalamic GABA levels and Occupational Manganese Neurotoxicity: Association with Exposure Levels and Brain MRI
    (Elsevier, 2017) Ma, Ruoyun E.; Ward, Eric J.; Yeh, Chien-Lin; Snyder, Sandy; Long, Zaiyang; Yavuz, Fulya Gokalp; Zauber, S. Elizabeth; Dydak, Ulrike; Department of Neurology, School of Medicine
    Excessive occupational exposure to Manganese (Mn) has been associated with clinical symptoms resembling idiopathic Parkinson’s disease (IPD), impairing cognitive and motor functions. Several studies point towards an involvement of the brain neurotransmitter system in Mn intoxication, which is hypothesized to be disturbed prior to onset of symptoms. Edited Magnetic Resonance Spectroscopy (MRS) offers the unique possibility to measure γ-amminobutyric acid (GABA) and other neurometabolites in vivo non-invasively in workers exposed to Mn. In addition, the property of Mn as Magnetic Resonance Imaging (MRI) contrast agent may be used to study Mn deposition in the human brain. In this study, using MRI, MRS, personal air sampling at the working place, work history questionnaires, and neurological assessment (UPDRS-III), the effects of chronic Mn exposure on the thalamic GABAergic system was studied in a group of welders (N = 39) with exposure to Mn fumes in a typical occupational setting. Two subgroups of welders with different exposure levels (Low: N = 26; mean air Mn = 0.13 ± 0.1 mg/m3; High: N = 13; mean air Mn = 0.23 ± 0.18 mg/m3), as well as unexposed control workers (N = 22, mean air Mn = 0.002 ± 0.001 mg/m3) were recruited. The group of welders with higher exposure showed a significant increase of thalamic GABA levels by 45% (p < 0.01, F(1,33) = 9.55), as well as significantly worse performance in general motor function (p < 0.01, F(1,33) = 11.35). However, welders with lower exposure did not differ from the controls in GABA levels or motor performance. Further, in welders the thalamic GABA levels were best predicted by past-12-months exposure levels and were influenced by the Mn deposition in the substantia nigra and globus pallidus. Importantly, both thalamic GABA levels and motor function displayed a non-linear pattern of response to Mn exposure, suggesting a threshold effect.
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    Thalamic GABA Predicts Fine Motor Performance in Manganese-Exposed Smelter Workers
    (Public Library of Science, 2014-02-04) Long, Zaiyang; Li, Xiang-Rong; Xu, Jun; Edden, Richard A. E.; Qin, Wei-Ping; Long, Li-Ling; Murdoch, James B.; Zheng, Wei; Jiang, Yue-Ming; Dydak, Ulrike; Radiology and Imaging Sciences, School of Medicine
    Overexposure to manganese (Mn) may lead to parkinsonian symptoms including motor deficits. The main inhibitory neurotransmitter gamma-aminobutyric acid (GABA) is known to play a pivotal role in the regulation and performance of movement. Therefore this study was aimed at testing the hypothesis that an alteration of GABA following Mn exposure may be associated with fine motor performance in occupationally exposed workers and may underlie the mechanism of Mn-induced motor deficits. A cohort of nine Mn-exposed male smelter workers from an Mn-iron alloy factory and 23 gender- and age-matched controls were recruited and underwent neurological exams, magnetic resonance spectroscopy (MRS) measurements, and Purdue pegboard motor testing. Short-echo-time MRS was used to measure N-Acetyl-aspartate (NAA) and myo-inositol (mI). GABA was detected with a MEGA-PRESS J-editing MRS sequence. The mean thalamic GABA level was significantly increased in smelter workers compared to controls (p = 0.009). Multiple linear regression analysis reveals (1) a significant association between the increase in GABA level and the duration of exposure (R(2) = 0.660, p = 0.039), and (2) significant inverse associations between GABA levels and all Purdue pegboard test scores (for summation of all scores R(2) = 0.902, p = 0.001) in the smelter workers. In addition, levels of mI were reduced significantly in the thalamus and PCC of smelter workers compared to controls (p = 0.030 and p = 0.009, respectively). In conclusion, our results show clear associations between thalamic GABA levels and fine motor performance. Thus in Mn-exposed subjects, increased thalamic GABA levels may serve as a biomarker for subtle deficits in motor control and may become valuable for early diagnosis of Mn poisoning.