Cortical Gray Matter Thickness and Volume Changes and Their Association with Memory Functions in Hyperthyroid Patients.

INTRODUCTION: Hyperthyroidism, characterized by excessive thyroid hormone production, is a common endocrine disorder that affects various physiological processes, including brain function. Recent advancements in neuroimaging techniques have enabled researchers to investigate structural alterations in the brain associated with hyperthyroidism. This study aimed to examine regional cortical thickness and cortical volume differences across the brain between hyperthyroid patients and control subjects. METHODS: We examined localized cortical thicknesses and volumes in 34 hyperthyroid patients and 35 control subjects with high-resolution T1-weighted images using FreeSurfer software and assessed group differences with analysis of covariance (covariates: age, sex, education, and total intracranial volume). Spearman and partial correlations were performed between clinical variables and cortical thicknesses/volumes and between neuropsychological scores and cortical thicknesses/volumes, respectively. RESULTS: Hyperthyroid patients exhibited significantly increased cortical thickness in bilateral superior temporal and superior frontal gyri, along with higher cortical volumes in various regions, including the right superior temporal gyrus, right superior parietal gyrus, right rostral and caudal middle frontal gyrus, and left superior frontal gyrus. Notably, thyroid hormones (fT3, fT4) correlated positively with cortical thicknesses and volumes in the superior temporal gyrus and superior frontal gyrus. Additionally, recognition memory scores negatively correlated with the right superior temporal gyrus and right superior frontal gyrus cortical thickness. CONCLUSION: The observed cortical thickening and increased cortical volume in specific brain areas provide new insights into the pathophysiological mechanism associated with brain impairment in hyperthyroidism.

Studies on metabolic alterations due to hypobaric hypoxia in serum using NMR spectroscopy.

INTRODUCTION: The main physiological challenge in high altitude environment is hypoxia which affects the aerobic metabolism reducing the energy supply. These changes may further progress towards extreme environment related diseases. Rarely has the high-altitude biology been studied using system sciences and omics high-throughput technologies. OBJECTIVE: In the present study, 1H-NMR-based metabolomics, along with multivariate analysis, were employed in a preclinical rat model to characterise the serum metabolic changes under chronic hypobaric hypoxia (HH) stress. MATERIAL AND METHODS: Rats were exposed to simulated hypobaric hypoxia equivalent of 6700 m above the sea level. The serum samples were collected from control and HH-exposure (7, 14, and 21 days) of hypobaric hypoxia. RESULTS AND DISCUSSION: The 1H-NMR metabolomics of the serum showed alterations in the metabolism of membranes, amino-acids altered cellular bioenergetics and osmoregulation. Multivariate statistical analysis revealed alterations in acetoacetate, choline, glutamine, acetate, betaine, ketone bodies and branched amino acid metabolites. CONCLUSION: Present findings establishes the fingerprint biomarkers for chronic environmental hypoxia which will help in understanding extreme environment related health problems, early detection and developing strategies to clinically address high altitude hypoxia.

Neuroprotective response and efficacy of intravenous administration of mesenchymal stem cells in traumatic brain injury mice.

Cellular transplantation of stem cells can be a beneficial treatment approach for neurodegenerative diseases such as traumatic brain injury (TBI). In this study, we investigated the proliferation and differentiation potential of infused mesenchymal stem cells (MSCs) after localisation at the injury site. We evaluated the appropriate homing of infused MSCs through immunohistochemistry, followed by Y-chromosome-specific polymerase chain reaction and fluorescent in situ hybridisation analyses. The proliferation and differentiation of infused MSCs were analysed using exogenous cell tracer 5'-bromo-2'-deoxyuridine (BrdU) labelling and neuronal specific markers, respectively. Structural and functional recovery in TBI mice were examined by performing magnetic resonance imaging and different behavioural assessments, respectively. Results demonstrated a significantly high number of BrdU-positive cells in the lesion region in the MSC-infused group compared with control and TBI groups. Infused MSCs were well differentiated into neural-like cells and expressed significantly more neural markers (neuronal nuclear antigen [NeuN], microtubule-associated protein 2 [MAP2] and glial fibrillary acid protein [GFAP]). Improved tissue abnormalities as well as functional behaviours were observed in MSC-infused TBI mice, implying the substantial proliferation and differentiation of infused MSCs. Our findings support the neuroprotective response and efficacy of MSCs after transplantation in TBI mice, and MSCs may serve as potential therapeutic candidates in regenerative medicine.

Evidence for regional hippocampal damage in patients with schizophrenia.

PURPOSE: Schizophrenia patients show cognitive and mood impairments, including memory loss and depression, suggesting damage in the brain regions. The hippocampus is a brain structure that is significantly involved in memory and mood function and shows impairment in schizophrenia. In the present study, we examined the regional hippocampal changes in schizophrenia patients using voxel-based morphometry (VBM), Freesurfer, and proton magnetic resonance spectroscopy (1H MRS) procedures. METHODS: 1H MRS and high-resolution T1-weighted magnetic resonance imaging were collected in both healthy control subjects (N = 28) and schizophrenia patients (N = 28) using 3-Tesla whole body MRI system. Regional hippocampal volume was analyzed using VBM and Freesufer procedures. The relative ratios of the neurometabolites were calculated using linear combination model (LCModel). RESULTS: Compared to controls, schizophrenia patients showed significantly decreased gray matter volume in the hippocampus. Schizophrenia patients also showed significantly reduced glutamate (Glu) and myo-inositol (mI) ratios in the hippocampus. Additionally, significant positive correlation between gray matter volume and Glu/tCr was also observed in the hippocampus in schizophrenia. CONCLUSION: Our findings provide an evidence for a possible association between structural deficits and metabolic alterations in schizophrenia patients.

Biological effects of iron oxide-protamine sulfate complex on mesenchymal stem cells and its relaxometry based labeling optimization for cellular MRI.

Mesenchymal stem cells (MSCs) are frequently used as a therapeutic, but reliable imaging technique to longitudinally evaluate the engraftment of transplanted cells is inadequate. For magnetic resonance imaging (MRI), it is essential to understand the technical competence of in vitro stem cells labeling with iron oxide with regard to its relaxation behavior and significance of its biological expressions. The purpose of the study was to optimize the effective labeling of MSCs with high transverse relaxivity iron oxide contrast agent with protamine sulfate and also evaluate the biological effects (phenotype and function) of labeled MSCs. Our results demonstrated that 50:3µg/ml of Fe-Pro complex containing 10% serum at an incubation time of 6h were ideal for effective in vitro labeling. Relaxometry study demonstrated that almost an 8-fold increase in relaxation rate (R2) was observed in labeled MSCs by comparing with unlabeled. Marginal alteration in Oct4 and CD146 genes, and phenotypic CD45 expressions were detected after labeling. T2-weighted images and histological analysis confirmed the homing of transplanted cells to the site of injury. The relaxometry based optimized labeling method of MSCs could be extrapolated for cellular MRI and may be useful in stem cell tracking in various pre-clinical and clinical studies.

Early monitoring and quantitative evaluation of macrophage infiltration after experimental traumatic brain injury: A magnetic resonance imaging and flow cytometric analysis.

The inflammatory response following traumatic brain injury (TBI) is regulated by phagocytic cells. These cells comprising resident microglia and infiltrating macrophages play a pivotal role in the interface between early detrimental and delayed beneficial effects of inflammation. The aim of the present study was to monitor the early effect of monocyte/phagocytic accumulation and further to explore its kinetics in TBI mice. Localized macrophage population was monitored using ultrasmall superparamagnetic iron oxide (USPIO) nanoparticle enhanced in vivo serial magnetic resonance imaging (MRI). Flow cytometry based gating study was performed to discriminate between resident microglia (Ly6G-CD11b+CD45low) and infiltrating macrophages (Ly6G-CD11b+CD45high) at the injury site. The T2* relaxation analysis revealed that maximum macrophage infiltration occurs between 66 and 72h post injury (42-48h post administration of USPIO) at the site of inflammation. This imaging data was well supported by iron oxide specific Prussian blue staining and macrophage specific F4/80 immunohistochemistry (IHC) analysis. Quantitative real-time PCR analysis found significant expression of monocyte chemoattractant protein-1 (MCP-1) at 72h post injury. Also, we found that flow cytometric analysis demonstrated a 7-fold increase in infiltrating macrophages around 72h post injuries as compared to control. The MR imaging in combination with flow cytometric analysis enabled the dynamic measurement of macrophage infiltration at the injury site. This study may help in setting an optimal time window to intervene and prevent damage due to inflammation and to increase the therapeutic efficacy.

Early detection of whole body radiation induced microstructural and neuroinflammatory changes in hippocampus: A diffusion tensor imaging and gene expression study.

Ionizing radiation is known to a cause systemic inflammatory response within hours of exposure that may affect the central nervous system (CNS). The present study was carried out to look upon the influence of radiation induced systemic inflammatory response in hippocampus within 24 hr of whole body radiation exposure. A Diffusion Tensor Imaging (DTI) study was conducted in mice exposed to a 5-Gy radiation dose through a 60 Co source operating at 2.496 Gy/min at 3 hr and 24 hr post irradiation and in sham-irradiated controls using 7 T animal MRI system. The results showed a significant decrease in Mean Diffusivity (MD), Radial Diffusivity (RD), and Axial Diffusivity (AD) in hippocampus at 24 hr compared with controls. Additionally, marked change in RD was observed at 3 hr. Increased serum C-Reactive Protein (CRP) level depicted an increased systemic/peripheral inflammation. The neuroinflammatory response in hippocampus was characterized by increased mRNA expression of IL-1ß, IL-6, and Cox-2 at the 24 hr time point. Additionally, in the irradiated group, reactive astrogliosis was illustrated, with noticeable changes in GFAP expression at 24 hr. Altered diffusivity and enhanced neuroinflammatory expression in the hippocampal region showed peripheral inflammation induced changes in brain. Moreover, a negative correlation between gene expression and DTI parameters depicted a neuroinflammation induced altered microenvironment that might affect water diffusivity. The study showed that there was an influence of whole body radiation exposure on hippocampus even during the early acute phase that could be reflected in terms of neuroinflammatory response as well as microstructural changes. © 2016 Wiley Periodicals, Inc.

Altered metabolites of the rat hippocampus after mild and moderate traumatic brain injury - a combined in vivo and in vitro 1 H-MRS study.

Traumatic brain injury (TBI) has been shown to affect hippocampus-associated learning, memory and higher cognitive functions, which may be a consequence of metabolic alterations. Hippocampus-associated disorders may vary depending on the severity of injury [mild TBI (miTBI) and moderate TBI (moTBI)] and time since injury. The underlying hippocampal metabolic irregularities may provide an insight into the pathological process following TBI. In this study, in vivo and in vitro proton magnetic resonance spectroscopy (1 H-MRS) data were acquired from the hippocampus region of controls and TBI groups (miTBI and moTBI) at D0 (pre-injury), 4 h, Day 1 and Day 5 post-injury (PI). In vitro MRS results indicated trauma-induced changes in both miTBI and moTBI; however, in vivo MRS showed metabolic alterations in moTBI only. miTBI and moTBI showed elevated levels of osmolytes indicating injury-induced edema. Altered levels of citric acid cycle intermediates, glutamine/glutamate and amino acid metabolism indicated injury-induced aberrant bioenergetics, excitotoxicity and oxidative stress. An overall similar pattern of pathological process was observed in both miTBI and moTBI, with the distinction of depleted N-acetylaspartate levels (indicating neuronal loss) at 4 h and Day 1 and enhanced lactate production (indicating heightened energy depletion leading to the commencement of the anaerobic pathway) at Day 5 in moTBI. To the best of our knowledge, this is the first study to investigate the hippocampus metabolic profile in miTBI and moTBI simultaneously using in vivo and in vitro MRS.

Study of neurometabolic and behavioral alterations in rodent model of mild traumatic brain injury: a pilot study.

Mild traumatic brain injury (mTBI) is the most common form of TBI (70-90%) with consequences of anxiety-like behavioral alterations in approximately 23% of mTBI cases. This study aimed to assess whether mTBI-induced anxiety-like behavior is a consequence of neurometabolic alterations. mTBI was induced using a weight drop model to simulate mild human brain injury in rodents. Based on injury induction and dosage of anesthesia, four animal groups were included in this study: (i) injury with anesthesia (IA); (ii) sham1 (injury only, IO); (iii) sham2 (only anesthesia, OA); and (iv) control rats. After mTBI, proton magnetic resonance spectroscopy (1 H-MRS) and neurobehavioral analysis were performed in these groups. At day 5, reduced taurine (Tau)/total creatine (tCr, creatine and phosphocreatine) levels in cortex were observed in the IA and IO groups relative to the control. These groups showed mTBI-induced anxiety-like behavior with normal cognition at day 5 post-injury. An anxiogenic effect of repeated dosage of anesthesia in OA rats was observed with normal Tau/tCr levels in rat cortex, which requires further examination. In conclusion, this mTBI model closely mimics human concussion injury with anxiety-like behavior and normal cognition. Reduced cortical Tau levels may provide a putative neurometabolic basis of anxiety-like behavior following mTBI.

Potential stem cell labeling ability of poly-L-lysine complexed to ultrasmall iron oxide contrast agent: An optimization and relaxometry study.

For non-invasive stem cells tracking through MRI, it is important to understand the efficiency of in vitro labeling of stem cells with iron oxide with regard to its relaxation behavior. In this study, we have carried out a pilot study of labeling mice mesenchymal stem cells (mMSCs) with ultrasmall superparamagnetic iron oxide (USPIO) entrapped with poly-L-lysine (PLL) in different ratios and incubated with different times. Our results demonstrated that 50:1.5 µg/ml of iron oxide and PLL at an incubation time of 6h with 10% serum concentration are sufficient enough for effective labeling. Optimized labeling showed that >98% of viability and <3% toxicity were observed at a total iron content of 11.8 pg/cell. In vitro relaxometry study showed that almost a 6.6 fold reduction in transverse relaxation time (T2) was observed after labeling as compared to unlabeled. IO-PLL complex was more effective than iron oxide alone in labeling and a detectable lower limit found to be hundred with optimized concentration. Significant increase in Oct-4 expression on day-3 after labeling was observed, whereas CD146 expression remains unchanged in real time RT-PCR. This optimized labeling method of MSCs may be very useful for cellular MRI and stem cells tracking studies.

Neurometabolic and structural alterations in rat brain due to acute hypobaric hypoxia: in vivo 1H MRS at 7 T.

In response to hypobaric hypoxia (HH), which occurs at high altitude, the brain undergoes deleterious changes at the structural and metabolite level. In vivo T2 weighted imaging (T2WI) and (1)H-MRS was performed to understand the structural and metabolic changes in the hippocampus region of rat brain. Data were acquired pre-exposure (baseline controls), immediately after exposure and subsequently at the first, fourth, seventh and 14th days post exposure at normoxia. T2 weighted images of rat brain showed hyperintensity in the CA2/CA3 region of the hippocampus 7 d after acute HH, which persisted till 14 d, probably indicating structural changes in the hippocampus. (1)H-MRS results showed no change in metabolite level immediately after acute HH exposure, but on the first day of normoxia the myo-inositol level was significantly decreased, possibly due to altered astrocyte metabolism. Metabolic alterations showing an increase in choline and decrease in glutamate on the fourth day of normoxia may be seen as a process of demyelination and loss of glutamate pool respectively. On the seventh and 14th days of normoxia, decreases in N-acetylaspartate, creatine and glutamine + glutamate were observed, which might be due to decreased viability of glutamatergic neurons. In vivo (1)H-MRS demonstrated early neurometabolic changes prior to probable structural changes post acute HH exposure. The extension of these studies will help in early risk assessment, developing intervention and strategies for combating HH related changes.

Assessment of abstract reasoning abilities in alcohol-dependent subjects: an fMRI study.

INTRODUCTION: Chronic alcohol abuse has been traditionally associated with impaired cognitive abilities. The deficits are most evident in higher order cognitive functions, such as abstract reasoning, problem solving and visuospatial processing. The present study sought to increase current understanding of the neuropsychological basis of poor abstract reasoning abilities in alcohol-dependent subjects using functional magnetic resonance imaging (fMRI). METHODS: An abstract reasoning task-based fMRI study was carried out on alcohol-dependent subjects (n = 18) and healthy controls (n = 18) to examine neural activation pattern. The study was carried out using a 3-T whole-body magnetic resonance scanner. Preprocessing and post processing was performed using SPM 8 software. RESULTS: Behavioral data indicated that alcohol-dependent subjects took more time than controls for performing the task but there was no significant difference in their response accuracy. Analysis of the fMRI data indicated that for solving abstract reasoning-based problems, alcohol-dependent subjects showed enhanced right frontoparietal neural activation involving inferior frontal gyrus, post central gyrus, superior parietal lobule, and occipito-temporal gyrus. CONCLUSIONS: The extensive activation observed in alcohol dependents as compared to controls suggests that alcohol dependents recruit additional brain areas to meet the behavioral demands for equivalent task performance. The results are consistent with previous fMRI studies suggesting decreased neural efficiency of relevant brain networks or compensatory mechanisms for the execution of task for showing an equivalent performance.

Motor function deficits in schizophrenia: an fMRI and VBM study.

INTRODUCTION: To investigate whether the motor functional alterations in schizophrenia (SZ) are also associated with structural changes in the related brain areas using functional magnetic resonance imaging (fMRI) and voxel-based morphometry (VBM). METHODS: A sample of 14 right-handed SZ patients and 14 right-handed healthy control subjects matched for age, sex, and education were examined with structural high-resolution T1-weighted MRI; fMRI images were obtained during right index finger-tapping task in the same session. RESULTS: fMRI results showed reduced functional activation in the motor areas (contralateral precentral and postcentral gyrus) and ipsilateral cerebellum in SZ subjects as compared to healthy controls (n = 14). VBM analysis also revealed reduced grey matter in motor areas and white matter reduction in cerebellum of SZ subjects as compared to controls. CONCLUSION: The present study provides an evidence for a possible association between structural alterations in the motor cortex and disturbed functional activation in the motor areas in persons affected with SZ during a simple finger-tapping task.

Effect of vitamin D supplementation on muscle energy phospho-metabolites: a ³¹P magnetic resonance spectroscopy-based pilot study.

There are several published reports on the prevalence of low vitamin D levels in otherwise healthy Indian population. Vitamin D deficiency has shown variable effect on muscle performance and strength but there is paucity of data on the effect of vitamin D deficiency on muscle energy metabolism. The present study was proposed to investigate the influence of severe vitamin D deficiency on high-energy metabolite levels in resting skeletal muscle and thereafter, monitor the response after vitamin D supplementation using ³¹P magnetic resonance spectroscopy (MRS). Study was conducted on 19 otherwise healthy subjects but with low serum 25(OH)D levels (<5 ng/ml). Subjects were supplemented with cholecalciferol at a dose of 60,000 IU/week for 12 weeks. MRS measurements of inorganic phosphate (Pi), phosphocreatine (PCr), phosphodiester (PDE) and ATP of the calf muscle were taken pre- and post-vitamin D supplementation. The study revealed significantly increased PCr/Pi ratio and decreased [Pi] and PDE/ATP ratio with raised serum 25(OH)D levels after 12 weeks of supplementation. The study indicates that serum 25(OH)D level plays an important role in improving the skeletal muscle energy metabolism and vitamin D deficiency might be one of the primary reasons for prevalence of low PCr/Pi ratio and high PDE values in normal Indian population as reported earlier. The findings of this preliminary study are highly encouraging and warrant further in-depth research, involving larger number of subjects of different age groups, regions and socio-economic sections of the society to further strengthen a correlation between vitamin D levels and muscle energy metabolism.

Comparative evaluation of brain neurometabolites and DTI indices following whole body and cranial irradiation: a magnetic resonance imaging and spectroscopy study.

Understanding early differential response of brain during whole body radiation or cranial radiation exposure is of significant importance for better injury management during accidental or intentional exposure to ionizing radiation. We investigated the early microstructural and metabolic profiles using in vivo diffusion tensor imaging (DTI) and proton magnetic resonance spectroscopy ((1)H MRS) following whole body and cranial radiation exposure of 8 Gy in mice using a 7.0 T animal MRI system and compared profiles with sham controls at days 1, 3, 5 and 10 post irradiation. A significant decrease in fractional anisotropy (FA) values was found in hippocampus, thalamic and hypothalamic regions (p < 0.05) in both whole body and cranial irradiated groups compared with controls, suggesting radiation induced reactive astrogliosis or neuroinflammatory response. In animals exposed to whole body radiation, FA was significantly decreased in some additional brain regions such as sensory motor cortex and corpus callosum in comparison with cranial irradiation groups and controls. Changes in FA were observed till day 10 post irradiation in both the groups. However, MRS study from hippocampus revealed changes only in the whole body radiation dose group. Significant reduction in the ratios of the metabolites myoinositol (mI, p = 0.02) and taurine (tau, p = 0.03) to total creatine were observed, and these metabolic alterations persisted till day 10 post irradiation. To the best of our knowledge this study has for the first time documented a comparative account of microstructural and metabolic aspects of whole body and cranial radiation induced early brain injury using in vivo MRI. Overall our findings suggest differential response at microstructure and metabolite levels following cranial or whole body radiation exposure.

Differential biochemical response of rat kidney towards low and high doses of NiCl2 as revealed by NMR spectroscopy.

Heavy metals are known for their associated nephrotoxicity and nickel is no exception. An integrated metabonomic approach, based on high-resolution (1) H NMR spectroscopy, was applied to determine the acute biochemical effects of NiCl(2) on the renal tissues of rats. Kidney homogenates from rats treated with NiCl(2) at two dose levels (4 and 20 mg kg(-1) b.w., i.p.) and those from controls were analysed using (1) H NMR spectroscopy and also assessed for antioxidant parameters at days 1, 3 and 5 post-dose. The major metabolite changes corresponding to nickel exposure were related to amino acids, osmolytes and energy metabolites. Differential responses were observed in (1) H NMR spectra with exposure to low and high doses of NiCl(2). For high doses, (1) H NMR spectral analysis revealed alterations in renal tissues, along with damage to the cortical and papillary region and depletion of renal osmolytes such as betaine, trimethyl amine oxide, myo-inositol and taurine, which persisted until day 5 post-dose. The metabolite profile of (1) H NMR spectra obtained from animals treated with lower dose of NiCl(2) initially increased as an immediate stress response and then showed signs of recovery with the passage of time. NMR spectral analysis was well corroborated with histopathological and oxidative stress results. Nickel-induced oxidative stress was observed in both groups of animals with increased levels of antioxidant parameters at initial time points, but continued to increase in the high-dose group. The present study shows a huge potential of metabonomics for mapping organ-based metabolic response during heavy metal toxicity.

Radiation-induced early changes in the brain and behavior: serial diffusion tensor imaging and behavioral evaluation after graded doses of radiation.

The nuclear arsenal and the use of nuclear technologies have enhanced the likelihood of whole-body/partial-body radiation exposure. The central nervous system is highly susceptible to even low doses of radiation. With the aim of detecting and monitoring the pathologic changes of radiation-induced damage in brain parenchyma, we used serial diffusion tensor magnetic resonance imaging (DTI) with a 7T magnetic resonance unit and neurobehavioral assessments mice irradiated with 3-, 5-, and 8-Gy doses of radiation. Fractional anisotropy (FA) and mean diffusivity (MD) values at each time point (baseline, day 1, day 5, and day 10) were quantified from hippocampus, thalamus, hypothalamus, cudate-putamen, frontal cortex, sensorimotor cortex, corpus callosum, cingulum, and cerebral peduncle. Behavioral tests were performed at baseline, day 5, and day 10. A decrease in FA values with time was observed in all three groups. At day 10, dose-dependent decreases in FA and MD values were observed in all of the regions compared with baseline. Behavioral data obtained in this study correlate with FA values. Radiation-induced affective disorders were not radiation dose dependent, insofar as the anxiety-like symptoms at the lower dose (3 Gy) mimics to the symptoms with the higher dose (8 Gy) level but not with the moderate dose. However, there was a dose-dependent decline in cognitive function as well as FA values. Behavioral data support the DTI indices, so it is suggested that DTI may be a useful tool for noninvasive monitoring of radiation-induced brain injury.

Brain functional connectivity in patients with hyperthyroidism after anti-thyroid treatment.

Thyroid disease is known to affect brain metabolism and cognitive function, although the recovery of thyroid-induced brain functional changes after treatment remains unclear. We aimed to investigate the alteration in brain functional connectivity and its correlation with neuropsychological variables in hyperthyroid patients before and after anti-thyroid treatment using a resting-state functional magnetic resonance imaging (rsfMRI) technique. This is a follow-up rsfMRI study of previous work that showed impaired brain functional connectivity in hyperthyroid patients compared to healthy controls. We included rsfMRI and neuropsychological data from 21 hyperthyroid patients out of an original cohort of 28 patients, before and after anti-thyroid treatment for 30 weeks. Functional connectivity analysis and neuropsychological scores were compared using paired t tests in patients at baseline and at follow-up. Patients showed an improvement in some of the memory (p < .05) and executive, visuospatial and motor (p < .001) functions after treatment, and also showed increased functional connectivity in the regions of the right fronto-parietal network, left fronto-parietal network, and default mode network (DMN) (p < .05). At follow-up, the functional connectivity of the right fronto-parietal network showed a significantly positive correlation with the recognition of objects memory score. The overall findings suggest that anti-thyroid treatment with carbimazole improves the functional connectivity within some of the resting state networks in the hyperthyroid patients, whereas the remaining networks still show impairment.

Study of acute biochemical effects of thallium toxicity in mouse urine by NMR spectroscopy.

Thallium (Tl) is a toxic heavy metal and its exposure to the human body causes physiological and biochemical changes due to its interference with potassium-dependent biological reactions. A high-resolution (1)H NMR spectroscopy based metabonomic approach has been applied for investigating acute biochemical effects caused by thallium sulfate (Tl(2)SO(4)). Male strain A mice were divided in three groups and received three doses of Tl(2)SO(4) (5, 10 and 20 mg kg(-1) b.w., i.p.). Urine samples collected at 3, 24, 72 and 96 h post-dose time points were analyzed by (1)H NMR spectroscopy. NMR spectral data were processed and analyzed using principal components analysis to represent biochemical variations induced by Tl(2)SO(4). Results showed Tl-exposed mice urine to have distinct metabonomic phenotypes and revealed dose- and time-dependent clustering of treated groups. The metabolic signature of urine analysis from Tl(2)SO(4)-treated animals exhibited an increase in the levels of creatinine, taurine, hippurate and ß-hydroxybutyrate along with a decrease in energy metabolites trimethylamine and choline. These findings revealed Tl-induced disturbed gut flora, membrane metabolite, energy and protein metabolism, representing physiological dysfunction of vital organs. The present study indicates the great potential of NMR-based metabonomics in mapping metabolic response for toxicology, which could ultimately lead to identification of potential markers for Tl toxicity.

Neurometabolite Changes in Hyperthyroid Patients Before and After Antithyroid Treatment: An in vivo 1H MRS Study.

Purpose: Patients with hyperthyroidism have frequent neuropsychiatric symptoms such as lack of attention, concentration, poor memory, impaired executive functions, depression, and anxiety. These neurocognitive impairments such as memory, attention, and executive functions appear to be associated with dysfunction in brain regions. This study was conducted to investigate the metabolic changes in the brain subcortical regions, i.e., posterior parietal cortex and dorsolateral prefrontal cortex (DLPFC), in patients with hyperthyroidism before and after antithyroid treatment using proton magnetic resonance spectroscopy (1H MRS). Materials and Methods: We collected neuropsychological and 1H MRS data from posterior parietal cortex and DLPFC, in both control (N = 30) and hyperthyroid (N = 30) patients. In addition, follow-up data were available for 19 patients treated with carbimazole for 30 weeks. The relative ratios of the neurometabolites were calculated using the Linear Combination Model (LCModel). Analysis of co-variance using Bonferroni correction was performed between healthy controls and hyperthyroid patients, and a paired t-test was applied in patients at baseline and follow-up. Spearman's rank-order correlation was used to analyze bivariate associations between thyroid hormone levels and metabolite ratios, and the partial correlation analysis was performed between neuropsychological scores and metabolite ratios, with age and sex as covariates, in the patients before and after treatment. Results: Our results revealed a significant decrease in choline/creatine [glycerophosphocholine (GPC) + phosphocholine (PCh)/creatine (tCr)] in both the posterior parietal cortex and DLPFC in hyperthyroid patients, and these changes were reversible after antithyroid treatment. The posterior parietal cortex also showed significantly reduced glutamate/creatine (Glu/tCr), (glutamate + glutamine)/creatine (Glx/tCr), and increased glutathione/creatine (GSH/tCr) ratios in the hyperthyroid patients over control subjects. In DLPFC, only (N-acetyl aspartate + N-acetyl aspartyl-glutamate)/creatine (NAA + NAAG)/tCr was increased in the hyperthyroid patients. After antithyroid treatment, (GPC + PCh)/tCr increased, and Glx/tCr decreased in both brain regions in the patients at follow-up. Gln/tCr in the posterior parietal cortex was decreased in patients at follow-up. Interestingly, (GPC + PCh)/tCr in DLPFC showed a significantly inverse correlation with free tri-iodothyronine (fT3) in hyperthyroid patients at baseline, whereas NAA/tCr showed positive correlations with fT3 and free thyroxine (fT4) in hyperthyroid patients before and after antithyroid treatment, in the posterior parietal cortex. In DLPFC, only (NAA + NAAG)/tCr showed positive correlations with fT3 and fT4 in the patients before treatment. Conclusion: The overall findings suggest that all the brain metabolite changes were not completely reversed in the hyperthyroid patients after antithyroid treatment, even after achieving euthyroidism.