Single-voxel Proton Magnetic Resonance Spectroscopy Research Articles

Precision of metabolite-selective MRS measurements of glutamate, GABA and glutathione: A review of human brain studies.

Single-voxel proton magnetic resonance spectroscopy (SV 1 H-MRS) is an in vivo noninvasive imaging technique used to detect neurotransmitters and metabolites. It enables repeated measurements in living participants to build explanatory neurochemical models of psychiatric symptoms and testing of therapeutic approaches. Given the tight link among glutamate, gamma-amino butyric acid (GABA), glutathione and glutamine within the cellular machinery, MRS investigations of neurocognitive and psychiatric disorders must quantify a network of metabolites simultaneously to capture the pathophysiological states of interest. Metabolite-selective sequences typically provide improved metabolite isolation and spectral modelling simplification for a single metabolite at a time. Non-metabolite-selective sequences provide information on all detectable human brain metabolites, but feature many signal overlaps and require complicated spectral modelling. Although there are short-echo time (TE) MRS sequences that do not use spectral editing and are optimised to target either glutamate, GABA or glutathione, these approaches usually imply a precision tradeoff for the remaining two metabolites. Given the interest in assessing psychiatric and neurocognitive diseases that involve excitation-inhibition imbalances along with oxidative stress, there is a need to survey the literature on the quantification precision of current metabolite-selective MRS techniques. In this review, we locate and describe 17 studies that report on the quality of simultaneously acquired MRS metabolite data in the human brain. We note several factors that influence the data quality for single-shot acquisition of multiple metabolites of interest using metabolite-selective MRS: (1) internal in vivo references; (2) brain regions of interests; (3) field strength of scanner; and/or (4) optimised acquisition parameters. We also highlight the strengths and weaknesses of various SV spectroscopy techniques that were able to quantify in vivo glutamate, GABA and glutathione simultaneously. The insights from this review will assist in the development of new MRS pulse sequences for simultaneous, selective measurements of these metabolites and simplified spectral modelling.

Molecular hydrogen modulates brain glutamate/GABA-glutamine cycle in overweight humans.

We evaluated whether 12-week intake of molecular hydrogen (H2) in 5 overweight adults (3 women; age: 50.2 ±11.9 years, body mass index: 29.4 ±2.1 kg/m2) affects brain levels of the glutamate-glutamine-GABA cycle, critical amino acid neurotransmitters in the mechanism of neuronal activation during appetite regulation. A 1.5-T single-voxel proton magnetic resonance spectroscopy was used to assess the tissue concentrations of relevant metabolites. The mean glutamate and glutamate-plus-glutamine levels at the posterior cingulate gyrus decreased significantly during the study; this was accompanied by a significant drop in GABA levels at left prefrontal white matter, and glutathione levels at anterior cingulate gyrus. No changes in the brain metabolites were found in the comparable group of overweight individuals (n = 4, 2 women; age: 41.0 ±13.9, BMI 26.8 ±1.3 kg/m2) followed-up in the past without this treatment. We showed a possible hydrogen-driven upregulation of neurotransmitters involved in appetite stimulation leading to hunger suppression and weight loss. Further studies analyzing appetite-controlling metabolic pathways affected by H2 would require monitoring of additional biomarkers of satiation and satiety during different feeding regimens.

Quantification of the neurochemical profile of the human putamen using STEAM MRS in a cohort of elderly subjects at 3 T and 7 T: Ruminations on the correction strategy for the tissue voxel composition.

The aim of this work is to quantify the metabolic profile of the human putamen in vivo in a cohort of elderly subjects using single-voxel proton magnetic resonance spectroscopy. To obtain metabolite concentrations specific to the putamen, we investigated a correction method previously proposed to account for the tissue composition of the volume of interest. We compared the method with the conventional approach, which a priori assumes equal metabolite concentrations in GM and WM. Finally, we compared the concentrations acquired at 3 Tesla (T) and 7 T MRI scanners. Spectra were acquired from 15 subjects (age: 67.7 ± 8.3 years) at 3 T and 7 T, using an ultra-short echo time, stimulated echo acquisition mode sequence. To robustly estimate the WM-to-GM metabolite concentration ratio, five additional subjects were measured for whom the MRS voxel was deliberately shifted from the putamen in order to increase the covered amount of surrounding WM. The concentration and WM-to-GM concentration ratio for 16 metabolites were reliably estimated. These ratios ranged from ~0.3 for γ-aminobutyric acid to ~4 for N-acetylaspartylglutamate. The investigated correction method led to significant changes in concentrations compared to the conventional method, provided that the ratio significantly differed from unity. Finally, we demonstrated that differences in tissue voxel composition cannot fully account for the observed concentration difference between field strengths. We provide not only a fully comprehensive quantification of the neurochemical profile of the putamen in elderly subjects, but also a quantification of the WM-to-GM concentration ratio. This knowledge may serve as a basis for future studies with varying tissue voxel composition, either due to tissue atrophy, inconsistent voxel positioning or simply when pooling data from different voxel locations.

Glutamate levels of the right and left anterior cingulate cortex in autistics adults

BackgroundThe neurobiology of Autism Spectrum Disorder (ASD) is still unknown. Alteration in glutamate metabolism might translate into an imbalance of the excitation/inhibition equilibrium of cortical networks that in turn are related to autistic symptoms, but previous studies using voxel located in bilateral anterior cingulate cortex (ACC) failed to show abnormalities in total glutamate level. Due to the functional differences in the right and left ACC, we sought to determine whether a difference between right and left ACC glutamate levels could be found when comparing ASD patients and control subjects. MethodsUsing single-voxel proton magnetic resonance spectroscopy (1H-MRS), we analyzed the glutamate + glutamine (Glx) concentrations in the left and right ACC of 19 ASD patients with normal IQs and 25 matched control subjects. ResultsNo overall group differences in Glx were shown, in the left ACC (p = 0.24) or in the right ACC (p = 0.11). ConclusionsNo significant alterations in Glx levels were detected in the left and right ACC in high-functioning autistic adults. In the excitatory/inhibitory imbalance framework, our data reinforce the critical need to analyze the GABAergic pathway, for better understanding of basic neuropathology in autism.

Bone density and bone marrow composition in transgender girls prior to pubertal blockade: A case series.

To determine bone mineral density (BMD) of transgender girls before pubertal blockade, and correlate with lifestyle and clinical variables. Six transfemale peri-pubertal girls had knee magnetic resonance imaging (MRI) with T1-weighted images and single-voxel proton magnetic resonance spectroscopy (MRS). BMD measurements were obtained via dual-energy X-ray absorptiometry. Questionnaires about physical activity, diet, and the Eating Attitudes Test (EAT-26) were completed. The T2 relaxation rate of water (R2=1/T2 in s -1) was correlated with scores on surveys. Three participants (50%) had a low bone mineral density for age based on total body less head Z-score less than -2; two participants (33%) had a low BMD for age at lumbar spine. All had EAT-26 scores below threshold for clinical concern. All participants self-reported regular exercise. Bone marrow MR variables (T1, fat fraction, unsaturation index and R2 of water) were not correlated with DXA measures. Participants had low BMD on beginning pubertal blockade. Clinicians should consider monitoring BMD among youth AMAB, a group at potential risk for poor bone health.

Evaluation of Proton MR Spectroscopy for the Study of the Tongue Tissue in Healthy Subjects and Patients With Tongue Squamous Cell Carcinoma: Preliminary Findings.

PurposeTo noninvasively assess spectroscopic and metabolic profiles of healthy tongue tissue and in an exploratory objective in nontreated and treated patients with tongue squamous cell carcinoma (SCC).MethodsFourteen healthy subjects (HSs), one patient with nontreated tongue SCC (NT-SCC), and two patients with treated tongue SCC (T-SCC) underwent MRI and single-voxel proton magnetic resonance spectroscopy (1H-MRS) evaluations (3 and 1.5T). Multi-echo-times 1H-MRS was performed at the medial superior part (MSP) and the anterior inferior part (AIP) of the tongue in HS, while 1H-MRS voxel was placed at the most aggressive part of the tumor for patients with tongue SCC. 1H-MRS data analysis yielded spectroscopic metabolite ratios quantified to total creatine.ResultsIn HS, compared to MSP and AIP, 1H-MRS spectra revealed higher levels of creatine, a more prominent and well-identified trimethylamine-choline (TMA-Cho) peak. However, larger prominent lipid peaks were better differentiated in the tongue MSP. Compared to HS, patients with NT-SCC exhibited very high levels of lipids and relatively higher values of TMA-Cho peak. Interestingly, patients with T-SCC showed almost nonproliferation activity. However, high lipids levels were measured, although they were relatively lower than lipids levels measured in patients with NT-SCC.ConclusionThe present study demonstrated the potential use of in-vivo 1H-MRS to noninvasively assess spectroscopic and metabolic profiles of the healthy tongue tissue in a spatial location-dependent manner. Preliminary results revealed differences between HS and patients with tongue NT-SCC as well as tongue T-SCC, which should be confirmed with more patients. 1H-MRS could be included, in the future, in the arsenal of tools for treatment response evaluation and noninvasive monitoring of patients with tongue SCC.

Single-Voxel Proton Magnetic Resonance Spectroscopy of the Thalamus in Idiopathic Epileptic Dogs and in Healthy Control Dogs.

The role of magnetic resonance spectroscopy (MRS) in the investigation of brain metabolites in epileptic syndromes in dogs has not been explored systematically to date. The aim of this study was to investigate metabolites in the thalamus in dogs affected by idiopathic epilepsy (IE) with and without antiepileptic drug treatment (AEDT) and to compare them to unaffected controls. Our hypothesis is that similar to humans with generalized epilepsy and loss of consciousness, N-acetyl aspartate (NAA) would be reduced, and glutamate–glutamine (Glx) would be increased in treated and untreated IE in comparison with the control group. In this prospective case–control study, Border Collie (BC) and Greater Swiss Mountain dog (GSMD) were divided into three groups: (1) healthy controls, IE with generalized tonic–clonic seizures with (2) and without (3) AEDT. A total of 41 BC and GSMD were included using 3 Tesla single-voxel proton MRS of the thalamus (PRESS localization, shortest TE, TR = 2000 ms, NSA = 240). After exclusion of 11 dogs, 30 dogs (18 IE and 12 healthy controls) remained available for analysis. Metabolite concentrations were estimated with LCModel using creatine as reference and compared using Kruskal–Wallis and Wilcoxon rank-sum tests. The Kruskal–Wallis test revealed significant differences in the NAA-to-creatine (p = 0.04) and Glx-to-creatine (p = 0.03) ratios between the three groups. The Wilcoxon rank-sum test further showed significant reduction in the NAA/creatine ratio in idiopathic epileptic dogs under AEDT compared to epileptic dogs without AEDT (p = 0.03) and compared to healthy controls (p = 0.03). In opposite to humans, Glx/creatine ratio was significantly reduced in dogs with IE under AEDT compared to epileptic dogs without AEDT (p = 0.03) and controls (p = 0.02). IE without AEDT and healthy controls did not show significant difference, neither in NAA/creatine (p = 0.60), nor in Glx-to-creatine (p = 0.55) ratio. In conclusion, MRS showed changes in dogs with IE and generalized seizures under AEDT, but not in those without AEDT. Based upon these results, MRS can be considered a useful advanced imaging technique for the evaluation of dogs with IE in the clinical and research settings.

Proton magnetic resonance spectroscopy assessment of neonatal brain metabolism during cardiopulmonary bypass surgery.

Here, we report on the development and performance of a robust 3-T single-voxel proton magnetic resonance spectroscopy (1 H MRS) experimental protocol and data analysis pipeline for quantifying brain metabolism during cardiopulmonary bypass (CPB) surgery in a neonatal porcine model, with the overall goal of elucidating primary mechanisms of brain injury associated with these procedures. The specific aims were to assess which metabolic processes can be reliably interrogated by 1 H MRS on a 3-T clinical scanner and to provide an initial assessment of brain metabolism during deep hypothermia cardiac arrest (DHCA) surgery and recovery. Fourteen neonatal pigs underwent CPB surgery while placed in a 3-T MRI scanner for 18, 28, and 37°C DHCA studies under hyperglycemic, euglycemic, and hypoglycemic conditions. Total imaging times, including baseline measurements, circulatory arrest (CA), and recovery averaged 3h/animal, during which 30-40 single-voxel 1 H MRS spectra (sLASER pulse sequence, TR/TE = 2000/30 ms, 64 or 128 averages) were acquired from a 2.2-cc right midbrain voxel. 1 H MRS at 3T was able to reliably quantify (1) anaerobic metabolism via depletion of brain glucose and the associated build-up of lactate during CA, (2) phosphocreatine (PCr) to creatine (Cr) conversion during CA and subsequent recovery upon reperfusion, (3) a robust increase in the glutamine-to-glutamate (Gln/Glu) ratio during the post-CA recovery period, and (4) a broadening of the water peak during CA. In vivo 1 H MRS at 3T can reliably quantify subtle metabolic brain changes previously deemed challenging to interrogate, including brain glucose concentrations even under hypoglycemic conditions, ATP usage via the conversion of PCr to Cr, and differential changes in Glu and Gln. Observed metabolic changes during CPB surgery of a neonatal porcine model provide new insights into possible mechanisms for prevention of neuronal injury.

Characterizing cerebral metabolite profiles in anorexia and bulimia nervosa and their associations with habitual behavior

Anorexia nervosa (AN) and bulimia nervosa (BN) are associated with altered brain structure and function, as well as increased habitual behavior. This neurobehavioral profile may implicate neurochemical changes in the pathogenesis of these illnesses. Altered glutamate, myo-inositol and N-acetyl aspartate (NAA) concentrations are reported in restrictive AN, yet whether these extend to binge-eating disorders, or relate to habitual traits in affected individuals, remains unknown. We therefore used single-voxel proton magnetic resonance spectroscopy to measure glutamate, myo-inositol, and NAA in the right inferior lateral prefrontal cortex and the right occipital cortex of 85 women [n = 22 AN (binge-eating/purging subtype; AN-BP), n = 33 BN, n = 30 controls]. To index habitual behavior, participants performed an instrumental learning task and completed the Creature of Habit Scale. Women with AN-BP, but not BN, had reduced myo-inositol and NAA concentrations relative to controls in both regions. Although patient groups had intact instrumental learning task performance, both groups reported increased routine behaviors compared to controls, and automaticity was related to reduced prefrontal glutamate and NAA participants with AN-BP. Our findings extend previous reports of reduced myo-inositol and NAA levels in restrictive AN to AN-BP, which may reflect disrupted axonal-glial signaling. Although we found inconsistent support for increased habitual behavior in AN-BP and BN, we identified preliminary associations between prefrontal metabolites and automaticity in AN-BP. These results provide further evidence of unique neurobiological profiles across binge-eating disorders.

Decreased Brain GABA Levels in Patients with Migraine Without Aura: An Exploratory Proton Magnetic Resonance Spectroscopy Study

Increasing neurophysiological studies had revealed that regional excitation-inhibition imbalance in the brain played a key role in the pathogenesis of migraine. This study aimed to explore the alterations in gamma-aminobutyric acid (GABA) and glutamate/glutamine complex (Glx) levels in the anterior cingulate gyrus (ACC) and medial prefrontal lobe (mPFC) of patients with migraine without aura (MWoA) and investigate the correlation between neurotransmitter levels and clinical indicators. A total of 28 patients with MWoA and 28 sex-, age-, and education level–matched healthy controls (HCs) underwent single-voxel proton magnetic resonance spectroscopy scanning at 3.0 Tesla. MEscher-Garwood Point RESolved Spectroscopy (MEGA-PRESS) sequence was performed to acquire the spectral data of GABA and Glx in the ACC and mPFC. The clinical indicators and anxiety-depression states of all participants were assessed. The acquired GABA signal contained the overlapping signals of macromolecules and homocarnosine, hence expressed as GABA+. The creatine (Cr) signal was applied as an endogenous reference. We observed that GABA+/Cr levels were significantly lower in ACC and mPFC of patients with MWoA than of HCs, with no significant difference in Glx levels. Negative correlations between GABA+/Cr levels and attack frequency were found in the ACC and mPFC regions of patients. These results suggested that there might be a close relationship between ACC and mPFC GABAergic neurons abnormalities and the pathophysiological mechanisms of MWoA. It might be beneficial to targeted treatment for patients with MWoA.

1H-MRS neurometabolites and associations with neurite microstructures and cognitive functions in amnestic mild cognitive impairment

Alzheimer’s disease (AD) pathogenesis is associated with alterations in neurometabolites and cortical microstructure. However, our understanding of alterations in neurochemicals in the prefrontal cortex and their relationship with changes in cortical microstructure in AD remains unclear. Here, we studied the levels of neurometabolites in the left dorsolateral prefrontal cortex (DLPFC) in healthy older adults and patients with amnestic Mild Cognitive Impairments (aMCI) using single-voxel proton-magnetic resonance spectroscopy (1H-MRS). N-acetyl aspartate (NAA), glutamate+glutamate (Glx), Myo-inositol (mI), and γ-aminobutyric acid (GABA) brain metabolite levels were quantified relative to total creatine (tCr = Cr + PCr). aMCI had significantly decreased NAA/tCr, Glx/tCr, NAA/mI, and increased mI/tCr levels compared with healthy controls. Further, we leveraged advanced diffusion MRI to extract neurite properties in the left DLPFC and found a significant positive correlation between NAA/tCr, related to neuronal intracellular compartment, and neurite density (ICVF, intracellular volume fraction), and a negative correlation between mI/tCr and neurite orientation (ODI) only in healthy older adults. These data suggest a potential decoupling in the relationship between neurite microstructures and NAA and mI concentrations in DLPFC in the early stage of AD. Together, our results confirm altered DLPFC neurometabolites in prodromal phase of AD and provide unique evidence regarding the imbalance in the association between neurometabolites and neurite microstructure in early stage of AD.

Weight gain as a risk factor for progressive neurochemical abnormalities in first episode mania patients: a longitudinal magnetic resonance spectroscopy study.

We previously reported that bipolar disorder (BD) patients with clinically significant weight gain (CSWG; ⩾7% of baseline weight) in the 12 months after their first manic episode experienced greater limbic brain volume loss than patients without CSWG. It is unknown whether CSWG is also a risk factor for progressive neurochemical abnormalities. We investigated whether 12-month CSWG predicted greater 12-month decreases in hippocampal N-acetylaspartate (NAA) and greater increases in glutamate + glutamine (Glx) following a first manic episode. In BD patients (n = 58) and healthy comparator subjects (HS; n = 34), we measured baseline and 12-month hippocampal NAA and Glx using bilateral 3-Tesla single-voxel proton magnetic resonance spectroscopy. We used general linear models for repeated measures to investigate whether CSWG predicted neurochemical changes. Thirty-three percent of patients and 18% of HS experienced CSWG. After correcting for multiple comparisons, CSWG in patients predicted a greater decrease in left hippocampal NAA (effect size = -0.52, p = 0.005). CSWG also predicted a greater decrease in left hippocampal NAA in HS with a similar effect size (-0.53). A model including patients and HS found an effect of CSWG on Δleft NAA (p = 0.007), but no diagnosis effect and no diagnosis × CSWG interaction, confirming that CSWG had similar effects in patients and HS. CSWG is a risk factor for decreasing hippocampal NAA in BD patients and HS. These results suggest that the well-known finding of reduced NAA in BD may result from higher body mass index in patients rather than BD diagnosis.

Magnetic resonance spectroscopy brain metabolites at term and 3-year neurodevelopmental outcomes in very preterm infants.

Noninvasive advanced neuroimaging and neurochemical assessment can identify subtle abnormalities and predict neurodevelopmental impairments. Our objective was to quantify white matter metabolite levels and evaluate their relationship with neurodevelopmental outcomes at age 3 years. Our study evaluated a longitudinal prospective cohort of very premature infants (<32 weeks gestational age) with single-voxel proton magnetic resonance spectroscopy from the centrum semiovale performed at term-equivalent age and standardized cognitive, verbal, and motor assessments at 3 years corrected age. We separately examined metabolite ratios in the left and right centrum semiovale. We also conducted an exploratory interaction analysis for high/low socioeconomic status (SES) to evaluate the relationship between metabolites and neurodevelopmental outcomes, after adjusting for confounders. We found significant relationships between choline/creatine levels in the left and right centrum semiovale and motor development scores. Exploratory interaction analyses revealed that, for infants with low SES, there was a negative association between choline/creatine in the left centrum semiovale and motor assessment scores at age 3 years. Brain metabolites from the centrum semiovale at term-equivalent age were associated with motor outcomes for very preterm infants at 3 years corrected age. This effect may be most pronounced for infants with low SES. Motor development at 3 years corrected age for very preterm infants is inversely associated with choline neurochemistry within the centrum semiovale on magnetic resonance spectroscopy at term-equivalent age, especially in infants with low socioeconomic status. No prior studies have studied metabolites in the centrum semiovale to predict neurodevelopmental outcomes at 3 years corrected age based on high/low socioeconomic status. For very preterm infants with lower socioeconomic status, higher choline-to-creatine ratio in central white matter is associated with worse neurodevelopmental outcomes.

Brain Metastases of Non-Small Cell Lung Cancer: Magnetic Resonance Spectroscopy for Clinical Outcome Assessment in Patients with Stereotactic Radiotherapy.

BackgroundBrain metastases (BM) are severe incidents among patients with non-small cell lung cancer (NSCLC) and have been associated with significant morbidity and decreased survival; thus, new methods are required to improve clinical management. Magnetic resonance spectroscopy (MRS) allows noninvasive measurements of biochemical information from tumor tissue, providing clinically useful imaging biomarkers. The primary aim of this study was to explore the application of MRS in the assessment of tumor prognosis after stereotactic radiotherapy in NSCLC patients with BM.Patients and MethodsMRS was performed on NSCLC patients attending Qingdao Center Hospital with suspected BM, and 68 patients were included in the survival analysis. The qualitative and quantitative parameters of MRS metabolites, such as choline (Cho), creatine (Cr), and N-acetyl-aspartate (NAA), were recorded. To select a cutoff for MRS metabolite parameters in the tumor and to distinguish patients who had recurrence, we performed an ROC curve analysis. Univariate and multivariate Cox regression analyses were used to assess the association between MRS metabolite parameters and clinical cancer prognosis.ResultsThe average age was 56 years. A total of 68 NSCLC patients underwent metabolic evaluation with single voxel proton MRS and were selected for retrospective analysis. According to the area under the curve (AUC) to predict recurrence, the MRS metabolite parameters were determined as Cho (AUC=0.550), Cr (AUC=0.415), NAA (AUC=0.524), NAA/Cr (AUC=0.600), Cho/Cr (AUC=0.723), and Cho/NAA (AUC=0.543). Cho and Cr predicted poor survival while Cho/Cr and NAA/Cr predicted improved survival (P<0.05). In the multivariate model with adjustment to establish the potential role of MRS metabolite parameters, Cho/Cr showed a significant association with OS (P=0.009) and PFS (P=0.006) after stereotactic radiotherapy.ConclusionThe positive results of this study indicate the predictive value of metabolic characteristics of BM detected with MRS for the outcome after stereotactic radiotherapy.

Interictal Single-Voxel Proton Magnetic Resonance Spectroscopy of the Temporal Lobe in Dogs With Idiopathic Epilepsy.

Proton magnetic resonance spectroscopy (H1-MRS) could provide insight into the metabolic pathophysiology of the temporal lobe of canine brain after seizure. Currently, there is no evidence-based data available on MRS of temporal lobe in dogs with idiopathic epilepsy (IE). The aim of this prospective, cross-sectional study was to evaluate the interictal metabolic activity of the temporal lobe in IE dogs compared to a control group with the use of H1-MRS. Ten healthy dogs and 27 client-owned dogs with IE underwent 1.5-Tesla magnetic resonance imaging (MRI) and single-voxel H1-MRS. The MRS studies were acquired as spin echoes with a repetition time (TR) of 2,000 ms and an echo time (TE) of 144 ms. A cubic voxel (10 ×10 ×10 mm) was positioned bilaterally into the region of the left and right temporal lobe, including a middle part of the hippocampus and the amygdala. The N-acetylaspartate (NAA)-to-creatine (NAA/Cr), NAA-to-choline (NAA/Cho), choline-to-creatine (Cho/Cr), and choline-to-NAA (Cho/NAA) ratios were determined in both hemispheres and compared to controls. No significant differences in all metabolite ratios between epileptic dogs and the control group could be found. A time-dependent decrease in the NAA/Cho ratio as well as an increase in the Cho/NAA ratio was found with proximity in time to the last seizure. We found no correlation between metabolite ratios and age or sex in this animal group. Time span from the last seizure to the acquisition of MRS significantly correlated with NAA/Cho and Cho/NAA ratio. We conclude that without a time relation, metabolite ratios in dogs with IE do not differ from those of the control group.

The Changes in 1H-MRS Metabolites in Cuprizone-Induced Model of Multiple Sclerosis: Effects of Prior Psychological Stress

Stress is considered as an important risk factor in the progression and the onset of many disorders such as multiple sclerosis. However, metabolite changes as a result of demyelination under the detrimental effects of stress are not well understood. Thus, 36 female Wistar rats (i.e., groups (1) no-cuprizone (Cont), (2) no-stress + cuprizone-treated (Cup), (3) physical stress + cuprizone-treated (P-Cup), (4) psychological stress + cuprizone-treated (Psy-Cup), (5) physical stress + no-cuprizone-treated (P), (6) psychological stress + no-cuprizone-treated (Psy)) were used in this study. Following induction of repetitive stress, cuprizone treatment was carried out for 6 weeks to instigate demyelination in all groups except the control animal. Relative metabolite concentrations of the brain were investigated by single-voxel proton magnetic resonance spectroscopy (reporting N-acetyl-aspartate (NAA), glycerophosphocholine with phosphocholine (tCho) relative to total creatine (tCr)). According to 1H-MRS, rats in the Cup group indicated a reduction in NAA/ tCr (p < 0.001) as well as tCho/ tCr (p < 0.05) compared with that in the Cont group. In contrast, in both stress + cuprizone-treated groups, NAA/tCr and tCho/tCr ratios remarkably increased versus the Cup group (p < 0.001) and the Cont group (p < 0.001 for the Psy-Cup group and p < 0.05 for the P-Cup group). Both P and Psy groups revealed normal metabolite concentrations similar to the Cont group 6 weeks post stress. Seemingly, in the case of cuprizone alone, decreased level of metabolites is mainly relevant to neuronal cell impairments. Meanwhile, as a result of oxidative stress enhancement due to stress exposure, oligodendrocyte becomes the main victim indicating the increased level of metabolite ratios.

Disrupted Coupling Between NAA and Functional Connectivity in Ventromedial Prefrontal Cortex of Drug-Naïve First-Episode Psychosis.

Ventromedial prefrontal cortex (vmPFC) is an important brain region involved in many psychological functions. Previous neuroimaging studies have shown disrupted function and altered metabolic level within vmPFC of schizophrenia (SCZ) patients. However, the linkage between the functional connectivity and its underlying neurobiological mechanism in SCZ remains unclear. In this study, we aimed to investigate the altered relationship between the functional connectivity strength (FCS) and metabolic concentrations within vmPFC in drug-naïve first-episode psychosis (FEP) patients using a combined functional magnetic resonance imaging (fMRI) and single-voxel proton magnetic resonance spectroscopy (1H- MRS) technique. There were 26 drug-naïve FEP patients and 27 matched healthy controls participated this study. We have found altered correlation between FCS and N-acetylaspartate (NAA) in drug-naïve FEP patients. In addition, the glutamate and glutamine compounds (Glx) and NAA concentrations were positively correlated with Positive and Negative Symptoms Scale (PANSS) total scores. Our findings revealed the disrupted functional-metabolic coupling within vmPFC in drug-naïve FEP patients and provided useful insights in understanding the etiology of SCZ.

1H MRS Measurement of Cortical GABA and Glutamate in Primary Insomnia and Major Depressive Disorder: Relationship to Sleep Quality and Depression Severity

BackgroundBoth Major Depressive Disorder (MDD) and Primary Insomnia (PI) have been linked to deficiencies in cortical γ-aminobutyric acid (GABA) and glutamate (Glu) thus suggesting a shared neurobiological link between these two conditions. The extent to which comorbid insomnia contributes to GABAergic or glutamatergic deficiencies in MDD remains unclear. MethodsWe used single-voxel proton magnetic resonance spectroscopy (1H MRS) at 4 Tesla to examine GABA+ and Glu relative to creatine (Cr) in the dorsal anterior cingulate cortex (dACC) and in the parieto-occipital cortex (POC) of 51 non-medicated adults with MDD, 24 adults with Primary Insomnia (PI), and 25 age- and sex-matched good sleeper controls (HC). Measures of depression severity and subjective and objective sleep quality were compared with 1H MRS metabolite measures. ResultsMDD subjects exhibited a 15% decrease in Glu/Cr in the dACC compared to HC. Within the MDD group, there was a trend inverse correlation between dACC Glu/Cr and anhedonia ratings. We observed no significant association between measures of sleep quality with dACC Glu/Cr in those with MDD. LimitationsThe protocol and data interpretation would have been enhanced by the recruitment of MDD subjects with a broader range of affect severity and a more comprehensive assessment of clinical features. ConclusionsThese findings support the role of cortical glutamatergic mechanisms in the pathophysiology of MDD. Insomnia severity did not further contribute to the relative deficiency of glutamatergic measures in MDD.

An exploratory proton MRS examination of gamma-aminobutyric acid, glutamate, and glutamine and their relationship to affective aspects of chronic pain

Veterans experience chronic pain more frequently than civilians. Identification of neurobiological mechanisms underlying the pathophysiology of chronic pain in a veteran population may aid in the development of novel treatment targets. In this pilot proof-of-concept study, veterans with chronic pain (N = 61) and no chronic pain (N = 19) completed clinical interviews, self-report questionnaires inquiring about pain history, interference of pain with daily life, and pain catastrophizing, as well as measures of depressive and anxious symptoms. Veterans also underwent single-voxel proton (1H) magnetic resonance spectroscopy (MRS) at 3 T in the anterior cingulate cortex (ACC) using a two-dimensional (2D) J-resolved point spectroscopy sequence. We found no group difference in neurometabolites between veterans with and without chronic pain; however, pain intensity, negative thinking about pain, and description of pain in affective terms were associated with lower GABA/Cre in the ACC. In addition, the Glu/GABA ratio in the ACC was positively associated with anxiety and depressive symptoms in veterans with chronic pain. Reductions in GABA in the ACC may contribute to increased pain intensity and greater pain catastrophizing in veterans with chronic pain. Furthermore, a disturbance in the excitatory-inhibitory balance may contribute to the anxious and depressive symptoms related to chronic pain. Given the pilot nature of the study, these findings must be considered preliminary.

The Assertive Brain: Anterior Cingulate Phosphocreatine plus Creatine Levels Correlate With Self-Directedness in Healthy Adolescents.

Despite various advances in the study of the neurobiological underpinnings of personality traits, the specific neural correlates associated with character and temperament traits are not yet fully understood. Therefore, this study aims to fill this gap by exploring the biochemical basis of personality, which is explored with the temperament and character inventory (TCI), during brain development in a sample of adolescents. Twenty-six healthy adolescents (aged between 13 and 21 years; 17 males and 9 females) with behavioral and emotional problems underwent a TCI evaluation and a 3T single-voxel proton magnetic resonance spectroscopy (1H MRS) acquisition of the anterior cingulate cortex (ACC). Absolute metabolite levels were estimated using LCModel: significant correlations between metabolite levels and selective TCI scales were identified. Specifically, phosphocreatine plus creatine (PCr+Cre) significantly correlated with self-directedness, positively, and with a self-transcendence (ST), negatively, while glycerophosphocholine plus phosphocholine (GPC+PC) and myo-inositol negatively correlated with ST. To the best of our knowledge, this is the first study reporting associations of brain metabolites with personality traits in adolescents. Therefore, our results represent a step forward for personality neuroscience within the study of biochemical systems and brain structures.