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Abstract Lithium is an effective augmenting agent for depressed patients with inadequate response to standard antidepressant therapy, but numerous adverse effects limit its use. We previously reported that a lithium-mimetic agent, ebselen, promoted a positive emotional bias—an indicator of potential antidepressant activity in healthy participants. We therefore aimed to investigate the effects of short-term ebselen treatment on emotional processing and brain neurochemistry in depressed patients with inadequate response to standard antidepressants. We conducted a double-blind, placebo-controlled 7-day experimental medicine study in 51 patients with major depressive disorder who were currently taking antidepressants but had an inadequate response to treatment. Participants received either ebselen 600 mg twice daily for seven days or identical matching placebo. An emotional testing battery, magnetic resonance spectroscopy and depression and anxiety rating scales were conducted at baseline and after seven days of treatment. Ebselen did not increase the recognition of positive facial expressions in the depressed patient group. However, ebselen increased the response bias towards fear emotion in the signal detection measurement. In the anterior cingulate cortex, ebselen significantly reduced the concentrations of inositol and Glx (glutamate+glutamine). We found no significant differences in depression and anxiety rating scales between visits. Our study did not find any positive shift in emotional bias in depressed patients with an inadequate response to antidepressant medication. We confirmed the ability of ebselen to lower inositol and Glx in the anterior cingulate cortex. These latter effects are probably mediated through inhibition of inositol monophosphatase and glutaminase respectively.

Quantifying an imaging modality’s ability to reproduce results is important for establishing its utility. In magnetic resonance spectroscopic imaging (MRSI), new acquisition protocols are regularly introduced which improve upon their precursors with respect to signal-to-noise ratio (SNR), total acquisition duration, and nominal voxel resolution. This study has quantified the within-subject and between-subject reproducibility of one such new protocol (reduced-field-of-view density-weighted concentric ring trajectory (rFOV-DW-CRT) MRSI) by calculating the coefficient of variance of data acquired from a test–retest experiment. The posterior cingulate cortex (PCC) and the right superior corona radiata (SCR) were selected as the regions of interest (ROIs) for grey matter (GM) and white matter (WM), respectively. CVs for between-subject and within-subject were consistently around or below 15% for Glx, tCho, and Myo-Ins, and below 5% for tNAA and tCr.

Background: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a chronic medical condition with no specific pharmacological treatment. Creatine, a nutrient essential for maintaining energy homeostasis in the cells, is a candidate for interventions in ME/CFS. Methods: Fourteen participants with ME/CFS received supplementation with 16 g creatine monohydrate for 6 weeks. Before starting creatine and on the last day of treatment, participants underwent brain magnetic resonance spectroscopy (MRS) scanning of the pregenual anterior cingulate cortex (pgACC) and dorsolateral prefrontal cortex (DLPFC), followed by symptom, cognition, and hand-grip strength assessments. Results: Eleven participants completed the study. Creatine treatment increased creatine concentration in both the pgACC and DLPFC (p = 0.004 and 0.012, respectively), decreased fatigue and reaction time (RT) on congruent and incongruent trials of the Stroop test (p = 0.036 and 0.014, respectively), and increased hand-grip strength (p = 0.0004). There was a positive correlation between increases in pgACC creatine and changes in RT on Stroop congruent and incongruent trials (p = 0.048 and p = 0.022, respectively). Creatine was well tolerated, and none of the participants stopped treatment. Conclusion: Creatine supplementation over six weeks in ME/CFS patients increased brain creatine and improved fatigue and some aspects of cognition. Despite its methodological limitations, this study encourages placebo-controlled investigations of creatine treatment in ME/CFS.

Summary: Proton-Magnetic Resonance Spectroscopy (MRS) is a non-invasive brain imaging technique used to measure the concentration of different neurochemicals. “Single-voxel” MRS data is typically acquired across several minutes, before individual transients are averaged through time to give a measurement of neurochemical concentrations. However, this approach is not sensitive to more rapid temporal dynamics of neurochemicals, including those that reflect functional changes in neural computation relevant to perception, cognition, motor control and ultimately behaviour. In this review we discuss recent advances in functional MRS (fMRS) that now allow us to obtain event-related measures of neurochemicals. Event-related fMRS involves presenting different experimental conditions as a series of trials that are intermixed. Critically, this approach allows spectra to be acquired at a time resolution in the order of seconds. Here we provide a comprehensive user guide for event-related task designs, choice of MRS sequence, analysis pipelines, and appropriate interpretation of event-related fMRS data. We raise various technical considerations by examining protocols used to quantify dynamic changes in GABA, the primary inhibitory neurotransmitter in the brain. Overall, we propose that although more data is needed, event-related fMRS can be used to measure dynamic changes in neurochemicals at a temporal resolution relevant to computations that support human cognition and behaviour.

Abstract Binocular vision is created by fusing the separate inputs arriving from the left and right eyes. ‘Eye dominance’ provides a measure of the perceptual dominance of one eye over the other. Theoretical models suggest that eye dominance is related to reciprocal inhibition between monocular units in the primary visual cortex, the first location where the binocular input is combined. As the specific inhibitory interactions in the binocular visual system critically depend on the presence of visual input, we sought to test the role of inhibition by measuring the inhibitory neurotransmitter GABA during monocular visual stimulation of the dominant and the non-dominant eye. GABA levels were measured in a single volume of interest in the early visual cortex, including V1 from both hemispheres, using a combined functional magnetic resonance imaging and magnetic resonance spectroscopy (combined fMRI-MRS) sequence on a 7-Tesla MRI scanner. Individuals with stronger eye dominance had a greater difference in GABAergic inhibition between the eyes. This relationship was present only when the visual system was actively processing sensory input and was not present at rest. We provide the first evidence that imbalances in GABA levels during ongoing sensory processing are related to eye dominance in the human visual cortex. Our finding supports the view that intracortical inhibition underlies normal eye dominance.

Ageing disrupts the finely tuned excitation/inhibition balance (E:I) across cortex via a natural decline in inhibitory tone (γ-amino butyric acid, GABA), causing functional decrements. However, in young adults, experimentally lowering GABA in sensorimotor cortex enhances a specific domain of sensorimotor function: adaptation memory. Here, we tested the hypothesis that as sensorimotor cortical GABA declines naturally with age, adaptation memory would increase, and the former would explain the latter. Results confirmed this prediction. To probe causality, we used brain stimulation to further lower sensorimotor cortical GABA during adaptation. Across individuals, how stimulation changed memory depended on sensorimotor cortical E:I. In those with low E:I, stimulation increased memory; in those with high E:I stimulation reduced memory. Thus, we identified a form of motor memory that is naturally strengthened by age, depends causally on sensorimotor cortex neurochemistry, and may be a potent target for motor skill preservation strategies in healthy ageing and neurorehabilitation.

The brain has a remarkable capacity to acquire and store memories that can later be selectively recalled. These processes are supported by the hippocampus which is thought to index memory recall by reinstating information stored across distributed neocortical circuits. However, the mechanism that supports this interaction remains unclear. Here, in humans, we show that recall of a visual cue from a paired associate is accompanied by a transient increase in the ratio between glutamate and GABA in visual cortex. Moreover, these excitatory-inhibitory fluctuations are predicted by activity in the hippocampus. These data suggest the hippocampus gates memory recall by indexing information stored across neocortical circuits using a disinhibitory mechanism.

Learning improves perceptual decisions by enhancing the brain's ability to filter noise and irrelevant information. Here, the authors show that GABAergic inhibition in decision-making circuits supports our ability to optimize perceptual judgments through learning and experience.

A reliable and practical renal-lipid quantification and imaging method is needed. Here, the feasibility of an accelerated MRSI method to map renal fat fractions (FF) at 3T and its repeatability were investigated. A 2D density-weighted concentric-ring-trajectory MRSI was used for accelerating the acquisition of 48 × 48 voxels (each of 0.25 mL spatial resolution) without respiratory navigation implementations. The data were collected over 512 complex-FID timepoints with a 1250 Hz spectral bandwidth. The MRSI sequence was designed with a metabolite-cycling technique for lipid–water separation. The in vivo repeatability performance of the sequence was assessed by conducting a test–reposition–retest study within healthy subjects. The coefficient of variation (CV) in the estimated FF from the test–retest measurements showed a high degree of repeatability of MRSI-FF (CV = 4.3 ± 2.5%). Additionally, the matching level of the spectral signature within the same anatomical region was also investigated, and their intrasubject repeatability was also high, with a small standard deviation (8.1 ± 6.4%). The MRSI acquisition duration was ~3 min only. The proposed MRSI technique can be a reliable technique to quantify and map renal metabolites within a clinically acceptable scan time at 3T that supports the future application of this technique for the non-invasive characterization of heterogeneous renal diseases and tumors.

The advantages of ultra-high-field (UHF ≥ 7T) MR have been demonstrated in a variety of MR acquisition modalities. Magnetic resonance spectroscopy (MRS) can particularly benefit from substantial gains in signal-to-noise ratio (SNR) and spectral resolution at UHF, enabling the quantification of numerous metabolites, including glutamate, glutamine, glutathione, and γ-aminobutyric acid that are relevant to psychiatric disorders. The aim of this review is to give an overview about the advantages and advances of UHF MRS and its application to psychiatric disorders. In order to provide a practical guide for potential applications of MRS at UHF, a literature review is given, surveying advantages and disadvantages of MRS at UHF. Key concepts, emerging technologies, practical considerations, and applications of UHF MRS are provided. Second, the strength of UHF MRS is demonstrated using some examples of its application in psychiatric disorders.

The oncogenes that are expressed in gliomas reprogram particular pathways of glucose, amino acids, and fatty acid metabolism. Mutations in isocitrate dehydrogenase genes (IDH1/2) in diffuse gliomas are associated with abnormally high levels of 2-hydroxyglutarate (2-HG) levels. The aim of this study was to determine whether metabolic reprogramming associated with IDH mutant gliomas leads to additional 1H MRS-detectable differences between IDH1 and IDH2 mutations, and to identify metabolites correlated with 2-HG. A total of 21 glioma patients (age= 37 ± 11, 13 males) were recruited for magnetic resonance spectroscopy (MRS) using semi-localization by adiabatic selective refocusing pulse sequence at an ultra-high-field (7T). For 20 patients, the tumor mutation subtype was confirmed by immunohistochemistry and DNA sequencing. LCModel analysis was applied for metabolite quantification. A two-sample t-test was used for metabolite comparisons between IDH1 (n = 15) and IDH2 (n = 5) mutant gliomas. The Pearson correlation coefficients between 2-HG and associated metabolites were calculated. A Bonferroni correction was applied for multiple comparison. IDH2 mutant gliomas have a higher level of 2-HG/tCho (total choline=phosphocholine+glycerylphosphorylcholine) (2.48 ± 1.01vs.0.72 ± 0.38, Pc < 0.001) and myo-Inositol/tCho (2.70 ± 0.90 vs. 1.46 ± 0.51, Pc = 0.011) compared to IDH1 mutation gliomas. Associated metabolites, myo-Inositol and glucose+taurine were correlated with 2-HG levels. These results show the improved characterization of the metabolic pathways in IDH1 and IDH2 gliomas for precision medicine.

(1)H magnetic resonance spectroscopy (MRS) is unique among imaging modalities because signals from several metabolites are measured during a single examination period. Each metabolite reflects a distinct intracellular process. Furthermore transverse (T2 ) relaxation times probe the viability of the cell microenvironment, e.g., the viscosity of the cellular fluids, the microscopic susceptibility distribution within the cells, and the iron content. In this study, T2s of brain metabolites were measured in the occipital lobe of eighteen young and fourteen elderly subjects at a field strength of 4 tesla. The T2s of N-acetylaspartate, total creatine, and total choline were 23%, 16% and 10% shorter in elderly than in young subjects. The findings of this study suggest that noninvasive detection of T2 provides useful biological information on changes in the cellular microenvironment that take place during aging.

Parkinson disease (PD) is characterized by the degeneration of nigrostriatal dopaminergic neurons. However, postmortem evidence indicates that the pathology of lower brainstem regions, such as the pons and medulla, precedes nigral involvement. Consistently, pontomedullary damage was implicated by structural and PET imaging in early PD. Neurochemical correlates of this early pathological involvement in PD are unknown.To map biochemical alterations in the brains of individuals with mild-moderate PD we quantified neurochemical profiles of the pons, putamen and substantia nigra by 7 tesla (T) proton magnetic resonance spectroscopy. Thirteen individuals with idiopathic PD (Hoehn & Yahr stage 2) and 12 age- and gender-matched healthy volunteers participated in the study. γ-Aminobutyric acid (GABA) concentrations in the pons and putamen were significantly higher in patients (N = 11, off medications) than controls (N = 11, p

Background: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a chronic medical condition with no specific pharmacological treatment. Creatine, a nutrient essential for maintaining energy homeostasis in the cells, is a candidate for interventions in ME/CFS. Methods: Fourteen participants with ME/CFS received supplementation with 16 g creatine monohydrate for 6 weeks. Before starting creatine and on the last day of treatment, participants underwent brain magnetic resonance spectroscopy (MRS) scanning of the pregenual anterior cingulate cortex (pgACC) and dorsolateral prefrontal cortex (DLPFC), followed by symptom, cognition, and hand-grip strength assessments. Results: Eleven participants completed the study. Creatine treatment increased creatine concentration in both the pgACC and DLPFC (p = 0.004 and 0.012, respectively), decreased fatigue and reaction time (RT) on congruent and incongruent trials of the Stroop test (p = 0.036 and 0.014, respectively), and increased hand-grip strength (p = 0.0004). There was a positive correlation between increases in pgACC creatine and changes in RT on Stroop congruent and incongruent trials (p = 0.048 and p = 0.022, respectively). Creatine was well tolerated, and none of the participants stopped treatment. Conclusion: Creatine supplementation over six weeks in ME/CFS patients increased brain creatine and improved fatigue and some aspects of cognition. Despite its methodological limitations, this study encourages placebo-controlled investigations of creatine treatment in ME/CFS. [ABSTRACT FROM AUTHOR]

Quantifying an imaging modality's ability to reproduce results is important for establishing its utility. In magnetic resonance spectroscopic imaging (MRSI), new acquisition protocols are regularly introduced which improve upon their precursors with respect to signal-to-noise ratio (SNR), total acquisition duration, and nominal voxel resolution. This study has quantified the within-subject and between-subject reproducibility of one such new protocol (reduced-field-of-view density-weighted concentric ring trajectory (rFOV-DW-CRT) MRSI) by calculating the coefficient of variance of data acquired from a test–retest experiment. The posterior cingulate cortex (PCC) and the right superior corona radiata (SCR) were selected as the regions of interest (ROIs) for grey matter (GM) and white matter (WM), respectively. CVs for between-subject and within-subject were consistently around or below 15% for Glx, tCho, and Myo-Ins, and below 5% for tNAA and tCr. [ABSTRACT FROM AUTHOR]

Purpose: To maximize acquisition bandwidth in zero echo time (ZTE) sequences, readout gradients are already switched on during the RF pulse, creating unwanted slice selectivity. The resulting image distortions are amplified especially when the anatomy of interest is not located at the isocenter. We aim to characterize off-center ZTE MRI of extremities such as the shoulder, knee, and hip, adjusting the carrier frequency of the RF pulse excitation for each TR. Methods: In ZTE MRI, radial encoding schemes are used, where the distorted slice profile due to the finite RF pulse length rotates with the k-space trajectory. To overcome these modulations for objects far away from the magnet isocenter, the frequency of the RF pulse is shifted for each gradient setting so that artifacts do not occur at a given off-center target position. The sharpness of the edges in the images were calculated and the ZTE acquisition with off-center excitation was compared to an acquisition with isocenter excitation both in phantom and in vivo off-center MRI of the shoulder, knee, and hip at 1.5 and 3T MRI systems. Results: Distortion and blurriness artifacts on the off-center MRI images of the phantom, in vivo shoulder, knee, and hip images were mitigated with off-center excitation without time or noise penalty, at no additional computational cost. Conclusion: The off-center excitation allows ZTE MRI of the shoulder, knee, and hip for high-bandwidth image acquisitions for clinical settings, where positioning at the isocenter is not possible.

Purpose: Multiple data formats in the MRS community currently hinder data sharing and integration. NIfTI‐MRS is proposed as a standard spectroscopy data format, implemented as an extension to the Neuroimaging informatics technology initiative (NIfTI) format. This standardized format can facilitate data sharing and algorithm development as well as ease integration of MRS analysis alongside other imaging modalities. Methods: A file format using the NIfTI header extension framework incorporates essential spectroscopic metadata and additional encoding dimensions. A detailed description of the specification is provided. An open‐source command‐line conversion program is implemented to convert single‐voxel and spectroscopic imaging data to NIfTI‐MRS. Visualization of data in NIfTI‐MRS is provided by development of a dedicated plugin for FSLeyes, the FMRIB Software Library (FSL) image viewer. Results: Online documentation and 10 example datasets in the proposed format are provided. Code examples of NIfTI‐MRS readers are implemented in common programming languages. Conversion software, spec2nii, currently converts 14 formats where data is stored in image‐space to NIfTI‐MRS, including Digital Imaging and Communications in Medicine (DICOM) and vendor proprietary formats. Conclusion: NIfTI‐MRS aims to solve issues arising from multiple data formats being used in the MRS community. Through a single conversion point, processing and analysis of MRS data are simplified, thereby lowering the barrier to use of MRS. Furthermore, it can serve as the basis for open data sharing, collaboration, and interoperability of analysis programs. Greater standardization and harmonization become possible. By aligning with the dominant format in neuroimaging, NIfTI‐MRS enables the use of mature tools present in the imaging community, demonstrated in this work by using a dedicated imaging tool, FSLeyes, for visualization. [ABSTRACT FROM AUTHOR]

A reliable and practical renal-lipid quantification and imaging method is needed. Here, the feasibility of an accelerated MRSI method to map renal fat fractions (FF) at 3T and its repeatability were investigated. A 2D density-weighted concentric-ring-trajectory MRSI was used for accelerating the acquisition of 48 × 48 voxels (each of 0.25 mL spatial resolution) without respiratory navigation implementations. The data were collected over 512 complex-FID timepoints with a 1250 Hz spectral bandwidth. The MRSI sequence was designed with a metabolite-cycling technique for lipid–water separation. The in vivo repeatability performance of the sequence was assessed by conducting a test–reposition–retest study within healthy subjects. The coefficient of variation (CV) in the estimated FF from the test–retest measurements showed a high degree of repeatability of MRSI-FF (CV = 4.3 ± 2.5%). Additionally, the matching level of the spectral signature within the same anatomical region was also investigated, and their intrasubject repeatability was also high, with a small standard deviation (8.1 ± 6.4%). The MRSI acquisition duration was ~3 min only. The proposed MRSI technique can be a reliable technique to quantify and map renal metabolites within a clinically acceptable scan time at 3T that supports the future application of this technique for the non-invasive characterization of heterogeneous renal diseases and tumors. [ABSTRACT FROM AUTHOR]

Abstract In humans, motor learning is underpinned by changes in sensorimotor network functional connectivity (FC). Unilateral contractions increase FC in the ipsilateral primary motor cortex (M1) and supplementary motor area (SMA); areas involved in motor planning and execution of the contralateral hand. Therefore, unilateral contractions are a promising approach to augment motor performance in the contralateral hand. In a within-participant, randomized, cross-over design, 15 right-handed adults had two magnetic resonance imaging (MRI) sessions, where functional-MRI and MR-Spectroscopic Imaging were acquired before and after repeated right-hand contractions at either 5% or 50% maximum voluntary contraction (MVC). Before and after scanning, response times (RTs) were determined in both hands. Nine minutes of 50% MVC contractions resulted in decreased handgrip force in the contracting hand, and decreased RTs and increased handgrip force in the contralateral hand. This improved motor performance in the contralateral hand was supported by significant neural changes: increased FC between SMA-SMA and increased FC between right M1 and right Orbitofrontal Cortex. At a neurochemical level, the degree of GABA decline in left M1, left and right SMA correlated with subsequent behavioural improvements in the left-hand. These results support the use of repeated handgrip contractions as a potential modality for improving motor performance in the contralateral hand.

Aim:Although monosodium glutamate is widely used in the food industry, it has effects in terms of teratogenicity, especially during pregnancy and embryogenesis. Although monosodium glutamate is widely used in the food industry, it has effects in terms of teratogenicity, especially during pregnancy and embryogenesis. Our study analyses the effect on the development of the notochord by giving monosodium glutamate to chicken egg embryos.Methods:The incubation and embryonic development follow-up of our study were held in the experimental animals laboratory of University of Health Sciences Turkey, Istanbul Bakirkoy Prof. Dr. Mazhar Osman Mental Health and Neurological Diseases Training and Research Hospital, and the preparation and microscopy of the samples were carried out in the Pathology Department of the Cerrahpasa Faculty of Medicine. 120 fertile, pathogen-free eggs were incubated at 75% humidity and 37.4±0.2 °C until embryos reached Hamburger and Hamilton stages 9-10 (30th hour). Eggs were divided into four groups. Group 1 consisted of uninjected eggs, group 2 consisted of eggs injected with saline (10 nL 0.9 NaCl), group 3 consisted of eggs injected with 15 mg/kg monosodium glutamate (MSG); and group 4 consisted of eggs injected at regular intervals.Results:The correlation values between height, dilatation, autolysis, chest, and lumbar diameters of embryos in all groups were examined. The mean embryo length was 1.0017±0.36 cm. The mean chest diameter was 20.70±14.45 cm. The mean lumbar diameter was 10.31±14.34 cm. When the groups were compared in terms of embryo length, it was observed that the groups given MSG were significantly shorter than the control and SF groups (p=0.00).Conclusion:The amount of MSG taken with food is important because it can affect the organs. Depending on the amount consumed, MSG may adversely affect notochord development.

Conventional proton MRS has been successfully utilized to noninvasively assess tissue biochemistry in conditions that result in large changes in metabolite levels. For more challenging applications, namely, in conditions which result in subtle metabolite changes, the limitations of vendor‐provided MRS protocols are increasingly recognized, especially when used at high fields (≥3 T) where chemical shift displacement errors, B0 and B1 inhomogeneities and limitations in the transmit B1 field become prominent. To overcome the limitations of conventional MRS protocols at 3 and 7 T, the use of advanced MRS methodology, including pulse sequences and adjustment procedures, is recommended. Specifically, the semiadiabatic LASER sequence is recommended when TE values of 25‐30 ms are acceptable, and the semiadiabatic SPECIAL sequence is suggested as an alternative when shorter TE values are critical. The magnetic field B0 homogeneity should be optimized and RF pulses should be calibrated for each voxel. Unsuppressed water signal should be acquired for eddy current correction and preferably also for metabolite quantification. Metabolite and water data should be saved in single shots to facilitate phase and frequency alignment and to exclude motion‐corrupted shots. Final averaged spectra should be evaluated for SNR, linewidth, water suppression efficiency and the presence of unwanted coherences. Spectra that do not fit predefined quality criteria should be excluded from further analysis. Commercially available tools to acquire all data in consistent anatomical locations are recommended for voxel prescriptions, in particular in longitudinal studies. To enable the larger MRS community to take advantage of these advanced methods, a list of resources for these advanced protocols on the major clinical platforms is provided. Finally, a set of recommendations are provided for vendors to enable development of advanced MRS on standard platforms, including implementation of advanced localization sequences, tools for quality assurance on the scanner, and tools for prospective volume tracking and dynamic linear shim corrections. [ABSTRACT FROM AUTHOR]

Purpose: The human cerebellum plays an important role in the functional activity of the cerebrum, ranging from motor to cognitive systems given its relaying role between the spinal cord and cerebrum. The cerebellum poses many challenges to Magnetic Resonance Spectroscopic Imaging (MRSI) due to its caudal location, susceptibility to physiological artifacts, and partial volume artifacts resulting from its complex anatomical structure. Thus, in the present study, we propose a high‐resolution MRSI acquisition scheme for the cerebellum. Methods: A zoom or reduced field of view (rFOV) metabolite‐cycled MRSI acquisition at 3 Tesla, with a grid of 48 × 48, was developed to achieve a nominal resolution of 62.5 μL. Single‐slice rFOV MRSI data were acquired from the cerebellum of 5 healthy subjects with a nominal resolution of 2.5 × 2.5 × 10 mm3 in 9.6 min. Spectra were quantified using the LCModel package. A spatially unbiased atlas template of the cerebellum was used to analyze metabolite distributions in the cerebellum. Results: The superior quality of the achieved spectra‐enabled generation of high‐resolution metabolic maps of total N‐acetylaspartate, total Creatine (tCr), total Choline (tCho), glutamate+glutamine, and myo‐inositol, with Cramér‐Rao lower bounds below 50%. A template‐based regions of interest (ROI) analysis resulted in spatially dependent metabolite distributions in 9 ROIs. The group‐averaged high‐resolution metabolite maps across subjects increased the contrast‐to‐noise ratio between cerebellum regions. Conclusion: These findings indicate that very high‐resolution metabolite probing of the cerebellum is feasible using rFOV or zoomed MRSI at 3 Tesla. [ABSTRACT FROM AUTHOR]

Purpose: To implement an accelerated MR‐acquisition method allowing to map T2∗ relaxation and absolute concentration of sodium within skeletal muscles at 3T. Methods: A fast‐UTE‐2D density‐weighted concentric‐ring‐trajectory 23Na‐MRSI technique was used to acquire 64 time points of FID with a spectral bandwidth of 312.5 Hz with an in‐plane resolution of 2.5 × 2.5 mm2 in ~15 min. The fast‐relaxing 23Na signal was localized with a single‐shot, inversion‐recovery‐based, non‐echo (SIRENE) outer volume suppression (OVS) method. The sequence was verified using simulation and phantom studies before implementing it in human calf muscles. To evaluate the 2D‐SIRENE‐MRSI (UTE = 0.55 ms) imaging performance, it was compared to a 3D‐MRI (UTE = 0.3 ms) sequence. Both data sets were acquired within 2 same‐day sessions to assess repeatability. The T2∗ values were fitted voxel‐by‐voxel using a biexponential model for the 2D‐MRSI data. Finally, intra‐subject coefficients of variation (CV) were estimated. Results: The MRSI‐FID data allowed us to map the fast and slow components of T2∗ in the calf muscles. The spatial distributions of 23Na concentration for both MRSI and 3D‐MRI acquisitions were significantly correlated (P <.001). The test–retest analysis rendered high repeatability for MRSI with a CV of 5%. The mean T2Fast∗ in muscles was 0.7 ± 0.1 ms (contribution fraction = 37%), whereas T2Slow∗ was 13.2 ± 0.2 ms (63%). The mean absolute muscle 23Na concentration calculated from the T2∗‐corrected data was 28.6 ± 3.3 mM. Conclusion: The proposed MRSI technique is a reliable technique to map sodium's absolute concentration and T2∗ within a clinically acceptable scan time at 3T. [ABSTRACT FROM AUTHOR]

Previous research has highlighted the role of glutamate and gamma-aminobutyric acid (GABA) in perceptual, cognitive, and motor tasks. However, the exact involvement of these neurochemical mechanisms in the chain of information processing, and across human development, is unclear. In a cross-sectional longitudinal design, we used a computational approach to dissociate cognitive, decision, and visuomotor processing in 293 individuals spanning early childhood to adulthood. We found that glutamate and GABA within the intraparietal sulcus (IPS) explained unique variance in visuomotor processing, with higher glutamate predicting poorer visuomotor processing in younger participants but better visuomotor processing in mature participants, while GABA showed the opposite pattern. These findings, which were neurochemically, neuroanatomically and functionally specific, were replicated ~21 mo later and were generalized in two further different behavioral tasks. Using resting functional MRI, we revealed that the relationship between IPS neurochemicals and visuomotor processing is mediated by functional connectivity in the visuomotor network. We then extended our findings to high-level cognitive behavior by predicting fluid intelligence performance. We present evidence that fluid intelligence performance is explained by IPS GABA and glutamate and is mediated by visuomotor processing. However, this evidence was obtained using an uncorrected alpha and needs to be replicated in future studies. These results provide an integrative biological and psychological mechanistic explanation that links cognitive processes and neurotransmitters across human development and establishes their potential involvement in intelligent behavior.

Purpose: To provide a rapid, noninvasive fat‐water separation technique that allows producing quantitative maps of particular lipid components. Methods: The calf muscles in 5 healthy adolescents (age 12‐16 years; body mass index = 20 ± 3 kg/m2) were scanned by two different fat fraction measurement methods. A density‐weighted concentric‐ring trajectory metabolite‐cycling MRSI technique was implemented to collect data with a nominal resolution of 0.25 mL within 3 minutes and 16 seconds. For comparative purposes, the standard Dixon technique was performed. The two techniques were compared using structural similarity analysis. Additionally, the difference in the distribution of each lipid over the adolescent calf muscles was assessed based on the MRSI data. Results: The proposed MRSI technique provided individual fat fraction maps for eight musculoskeletal lipid components identified by LCModel analysis (IMC/L [CH3], EMCL [CH3], IMC/L [CH2]n, EMC/L [CH2]n, IMC/L [CH2–CH], EMC/L [CH2–CH], IMC/L [–CH=CH–], and EMC/L [–CH=CH–]) with mean structural similarity indices of 0.19, 0.04, 0.03, 0.50, 0.45, 0.04, 0.07, and 0.12, respectively, compared with the maps generated by the used Dixon method. Further analysis of voxels with zero structural similarity demonstrated an increased sensitivity of fat fraction lipid maps from the data acquired using this MRSI technique over the standard Dixon technique. The lipid spatial distribution over calf muscles was consistent with previously published findings in adults. Conclusion: This MRSI technique can be a useful tool when individual lipid fat fraction maps are desired within a clinically acceptable time and with a nominal spatial resolution of 0.25 mL. [ABSTRACT FROM AUTHOR]

Experience and training are known to boost our skills and mold the brain's organization and function. Yet, structural plasticity and functional neurotransmission are typically studied at different scales (large-scale networks, local circuits), limiting our understanding of the adaptive interactions that support learning of complex cognitive skills in the adult brain. Here, we employ multimodal brain imaging to investigate the link between microstructural (myelination) and neurochemical (GABAergic) plasticity for decision-making. We test (in males, due to potential confounding menstrual cycle effects on GABA measurements in females) for changes in MRI-measured myelin, GABA, and functional connectivity before versus after training on a perceptual decision task that involves identifying targets in clutter. We demonstrate that training alters subcortical (pulvinar, hippocampus) myelination and its functional connectivity to visual cortex and relates to decreased visual cortex GABAergic inhibition. Modeling interactions between MRI measures of myelin, GABA, and functional connectivity indicates that pulvinar myelin plasticity interacts-through thalamocortical connectivity-with GABAergic inhibition in visual cortex to support learning. Our findings propose a dynamic interplay of adaptive microstructural and neurochemical plasticity in subcortico-cortical circuits that supports learning for optimized decision-making in the adult human brain.

We investigated the relationship between neurochemical and hemodynamic responses as a function of image contrast in the human primary visual cortex (VI). Simultaneously acquired BOLD-fMRI and single voxel proton MR spectroscopy signals were measured in VI of 24 healthy human participants of either sex at 7 tesla field strength, in response to presentations (64 s blocks) of different levels of image contrast (3%, 12.5%, 50%, 100%). Our results suggest that complementary measures of neurotransmission and energy metabolism are in partial agreement: BOLD and glutamate signals were linear with image contrast; however, a significant increase in glutamate concentration was evident only at the highest intensity level. In contrast, GABA signals were steady across all intensity levels. These results suggest that neurochemical concentrations are maintained at lower ranges of contrast levels, which match the statistics of natural vision, and that high stimulus intensity may be critical to increase sensitivity to visually modulated glutamate signals in the early visual cortex using MR spectroscopy. [ABSTRACT FROM AUTHOR]

Background: Spinocerebellar ataxia type 1 (SCA1) causes progressive degeneration of the cerebellum and brainstem. Volumetric magnetic resonance imaging (MRI) was shown to be more sensitive to disease progression than the most sensitive clinical measure, the Scale for the Assessment and Rating of Ataxia (SARA), in longitudinal studies, and magnetic resonance spectroscopy (MRS) was shown to detect neurochemical abnormalities with high sensitivity cross‐sectionally in SCA1. Objectives: The objectives of this study were to compare the sensitivities to change of volumetric MRI, MRS, and SARA in a 3‐year longitudinal study in SCA1. Methods: A total of 16 early‐to‐moderate stage patients with SCA1 (SARA 0‐14) and 21 matched healthy participants were scanned up to 3 times with 1.5‐year intervals. Ataxia severity was assessed with SARA. T1‐weighted images and magnetic resonance spectra from the cerebellar vermis, cerebellar white matter, and pons were acquired at 3T. Results: The pontine total N‐acetylaspartate‐to‐myo‐inositol ratio was the most sensitive MRS measure to change (−3.9 ± 4.6%/yr in SCA1 vs. −0.3 ± 3.5%/yr in controls; P < 0.02), and the pontine volume was the most sensitive MRI measure to change (−2.6 ± 1.2%/yr in SCA1 vs. −0.1 ± 1.2 in controls; P < 0.02). Effect size (mean percent change/standard deviation of percent change) of pontine volume was highest (−2.13) followed by pontine N‐acetylaspartate‐to‐myo‐inositol ratio (−0.84) and SARA (+0.60). The pontine N‐acetylaspartate‐to‐myo‐inositol ratio was abnormal for 1 premanifest patient at all visits and predicted study withdrawal as a result of disease progression in 3 patients. Conclusion: Both MRI and MRS were more sensitive to disease progression than SARA in SCA1. Pontine volume was most sensitive to change, whereas MRS may have more sensitivity at the premanifest stage and predictive value for disease progression. [ABSTRACT FROM AUTHOR]

Proton MRS (1H MRS) provides noninvasive, quantitative metabolite profiles of tissue and has been shown to aid the clinical management of several brain diseases. Although most modern clinical MR scanners support MRS capabilities, routine use is largely restricted to specialized centers with good access to MR research support. Widespread adoption has been slow for several reasons, and technical challenges toward obtaining reliable good‐quality results have been identified as a contributing factor. Considerable progress has been made by the research community to address many of these challenges, and in this paper a consensus is presented on deficiencies in widely available MRS methodology and validated improvements that are currently in routine use at several clinical research institutions. In particular, the localization error for the PRESS localization sequence was found to be unacceptably high at 3 T, and use of the semi‐adiabatic localization by adiabatic selective refocusing sequence is a recommended solution. Incorporation of simulated metabolite basis sets into analysis routines is recommended for reliably capturing the full spectral detail available from short TE acquisitions. In addition, the importance of achieving a highly homogenous static magnetic field (B0) in the acquisition region is emphasized, and the limitations of current methods and hardware are discussed. Most recommendations require only software improvements, greatly enhancing the capabilities of clinical MRS on existing hardware. Implementation of these recommendations should strengthen current clinical applications and advance progress toward developing and validating new MRS biomarkers for clinical use. [ABSTRACT FROM AUTHOR]

The posterior cingulate cortex (PCC) and corpus callosum (CC) are susceptible to trauma, but injury often evades detection. PCC Metabolic disruption may predict CC white matter tract injury and the secondary cascade responsible for progression. While the time frame for the secondary cascade remains unclear in humans, the first 24 h (hyper-acute phase) are crucial for life-saving interventions. Objectives: To test whether Magnetic Resonance Imaging (MRI) markers are detectable in the hyper-acute phase and progress after traumatic brain injury (TBI) and whether alterations in these parameters reflect injury severity. Methods: Spectroscopic and diffusion-weighted MRI data were collected in 18 patients with TBI (within 24 h and repeated 7–15 days following injury) and 18 healthy controls (scanned once). Results: Within 24 h of TBI N-acetylaspartate was reduced (F = 11.43, p = 0.002) and choline increased (F = 10.67, p = 0.003), the latter driven by moderate-severe injury (F = 5.54, p = 0.03). Alterations in fractional anisotropy (FA) and axial diffusivity (AD) progressed between the two time-points in the splenium of the CC (p = 0.029 and p = 0.013). Gradual reductions in FA correlated with progressive increases in choline (p = 0.029). Conclusions: Metabolic disruption and structural injury can be detected within hours of trauma. Metabolic and diffusion parameters allow identification of severity and provide evidence of injury progression. [ABSTRACT FROM AUTHOR]

Background: Lamotrigine is a useful treatment in bipolar depression but requires several weeks of dose titration before its clinical effects can be assessed. Animal experimental studies suggest that lamotrigine lowers glutamate release. The aim of the current study was to assess the effect of lamotrigine on brain glutamate in depressed bipolar patients and to determine whether baseline glutamate could be used to predict clinical response.Methods: We studied 21 bipolar patients who received lamotrigine treatment for a current episode of depression. Before starting lamotrigine and after 10-12 weeks treatment, patients underwent proton magnetic resonance spectroscopy (MRS) scanning at 3 Tesla where levels of glutamate (measured as Glx) were determined in anterior cingulate cortex (ACC).Results: Overall, lamotrigine treatment had no significant effect on Glx levels in ACC. However, in patients who responded clinically to lamotrigine treatment Glx concentrations were significantly increased. Baseline levels of Glx did not predict response to lamotrigine.Limitations: The main limitation of the study was the modest sample size. Most patients were medicated which may have modified the effect of lamotrigine on glutamate activity. MRS at 3T cannot give a reliable estimate of glutamate separate from its main metabolite, glutamine, and thus changes in Glx may not give a precise estimate of effects of lamotrigine on glutamate itself.Conclusion: Lamotrigine does not appear to have a direct effect on glutamate levels in ACC in bipolar patients. However, therapeutic improvement during lamotrigine was associated with increased Glx, suggesting that alterations in glutamatergic activity might be related to recovery from bipolar depression. [ABSTRACT FROM AUTHOR]

Key points: The ability to learn new motor skills is supported by plasticity in the structural and functional organisation of the primary motor cortex in the human brain.Changes inhibitory to signalling by GABA are thought to be crucial in inducing motor cortex plasticity.This study used magnetic resonance spectroscopy (MRS) to quantify the concentration of GABA in human motor cortex during a period of motor learning, as well as during a period of movement and a period at rest.We report evidence for a reduction in the MRS‐measured concentration of GABA specific to learning. Further, the GABA concentration early in the learning task was strongly correlated with the magnitude of subsequent learning: higher GABA concentrations were associated with poorer learning.The results provide initial insight into the neurochemical correlates of cortical plasticity associated with motor learning, specifically relevant in therapeutic efforts to induce cortical plasticity during recovery from stroke. The ability to learn novel motor skills is a central part of our daily lives and can provide a model for rehabilitation after a stroke. However, there are still fundamental gaps in our understanding of the physiological mechanisms that underpin human motor plasticity. The acquisition of new motor skills is dependent on changes in local circuitry within the primary motor cortex (M1). This reorganisation has been hypothesised to be facilitated by a decrease in local inhibition via modulation of the neurotransmitter GABA, but this link has not been conclusively demonstrated in humans. Here, we used 7 T magnetic resonance spectroscopy to investigate the dynamics of GABA concentrations in human M1 during the learning of an explicit, serial reaction time task. We observed a significant reduction in GABA concentration during motor learning that was not seen in an equivalent motor task lacking a learnable sequence, nor during a passive resting task of the same duration. No change in glutamate was observed in any group. Furthermore, M1 GABA measured early in task performance was strongly correlated with the degree of subsequent learning, such that greater inhibition was associated with poorer subsequent learning. This result suggests that higher levels of cortical inhibition may present a barrier that must be surmounted in order to achieve an increase in M1 excitability, and hence encoding of a new motor skill. These results provide strong support for the mechanistic role of GABAergic inhibition in motor plasticity, raising questions regarding the link between population variability in motor learning and GABA metabolism in the brain. Key points: The ability to learn new motor skills is supported by plasticity in the structural and functional organisation of the primary motor cortex in the human brain.Changes inhibitory to signalling by GABA are thought to be crucial in inducing motor cortex plasticity.This study used magnetic resonance spectroscopy (MRS) to quantify the concentration of GABA in human motor cortex during a period of motor learning, as well as during a period of movement and a period at rest.We report evidence for a reduction in the MRS‐measured concentration of GABA specific to learning. Further, the GABA concentration early in the learning task was strongly correlated with the magnitude of subsequent learning: higher GABA concentrations were associated with poorer learning.The results provide initial insight into the neurochemical correlates of cortical plasticity associated with motor learning, specifically relevant in therapeutic efforts to induce cortical plasticity during recovery from stroke. [ABSTRACT FROM AUTHOR]

Objective: Meningiomas are the most common primary intracranial tumors in adults that account for 36% of primary tumors. Treatment options other than surgery and radiotherapy are necessary for meningioma. Immune checkpoint molecules (ICM) are modulators that regulate the proper response of the immune system. Lymphocyte activation gene-3 (LAG-3), T-cell immunoglobulin and mucin domain containing-3 (TIM-3), and the cluster of differentiation 38 (CD38) are known ICMs. This study hypothesized the relationship between meningiomas of different histopathological grades and the levels of these three ICMs. Additionally, the therapeutic potential of these molecules was investigated. Material and Methods: This study re-evaluated 25 specimens diagnosed as meningioma. Tissues are classified according to LAG-3, TIM-3, and CD38 levels. Age, gender, surgery date, tumor type, and subtype, histopathologically malignant grade, radiological tumor size, and presence of edema were recorded in all patients. All data were statistically compared. Results: This study included the specimens of 25 patients, of whom 9 were males and 16 were females. LAG-3 and CD38 levels were significantly higher in tumors bigger than 6 cm. Conclusion: This study is the first to investigate LAG-3, TIM-3, and CD38 levels in meningiomas and found a significant correlation between LAG-3 levels and meningioma size. No significant correlation was found with other data. However, the number of patients in our study was insufficient. Therefore, larger patient groups may yield more significant results.

Aim:Intracranial pressure may increase due to reasons such as head trauma, intracranial hematoma, cerebral infarction, and cerebral edema. Decompressive craniectomy (DC) may be preferred in the treatment. Our study aims to examine the time of DC and the effect of pupil diameter and midline shift on mortality.Methods:Data from the hospital automation system and patient file records were retrospectively reviewed between 2017 and 2019, and 57 patients who underwent DC for raised intracranial pressure. Fifty-seven patients who underwent DC, whose neurological examination and pupil diameter were recorded after increased intracranial pressure, were evaluated.Results:The mean age of 57 patients was 50.38±19.91 years. The patients’ mean preoperative Glasgow coma score (GCS) was 8.85±3.6 and the mean GCS at discharge was 8.96±6.0. The mean cranial midline shifts of the patients were 7.88±5.35. 49.1% of the patients who underwent DC survived.Conclusion:Mortality rate is lower in patients who underwent DC compared to patients with isochoric pupil, anisocoric, and mid dilated patients. The timing of DC is important in terms of its effect on mortality.

Abstract Several scientific, engineering, and medical advancements are based on breakthroughs made by people who excel in mathematics. Our current understanding of the underlying brain networks stems primarily from anatomical and functional investigations, but our knowledge of how neurotransmitters subserve numerical skills, the building block of mathematics, is scarce. Using 1H magnetic resonance spectroscopy (N = 54, 3T, semi-LASER sequence, TE = 32 ms, TR = 3.5 s), the study examined the relation between numerical skills and the brain’s major inhibitory (GABA) and excitatory (glutamate) neurotransmitters. A negative association was found between the performance in a number sequences task and the resting concentration of GABA within the left intraparietal sulcus (IPS), a key region supporting numeracy. The relation between GABA in the IPS and number sequences was specific to (1) parietal but not frontal regions and to (2) GABA but not glutamate. It was additionally found that the resting functional connectivity of the left IPS and the left superior frontal gyrus was positively associated with number sequences performance. However, resting GABA concentration within the IPS explained number sequences performance above and beyond the resting frontoparietal connectivity measure. Our findings further motivate the study of inhibition mechanisms in the human brain and significantly contribute to our current understanding of numerical cognition's biological bases.