Abstract The use of sequential proton magnetic resonance spectroscopy (MRS) to follow glutamate and gamma‐aminobutyric acid (GABA) changes during functional task‐based paradigms, functional MRS ...(fMRS), has increased. This technique has been used to investigate GABA dynamics during both sensory and behavioural tasks, usually with long ‘block design’ paradigms. Recently, there has been an increase in interest in the use of short stimuli and ‘event‐related’ tasks. While changes in glutamate can be readily followed by collecting multiple individual transients (or shots), measurement of GABA, especially at 3 T, is usually performed using editing techniques like Mescher–Garwood point‐resolved spectroscopy (MEGA‐PRESS), which by its nature is a dual shot approach. This poses problems when considering an event‐related experiment, where it is unclear when GABA may change, or how this may affect the individual subspectra of the MEGA‐PRESS acquisition. To address this issue, MEGA‐PRESS data were simulated to reflect the effect of a transient change in GABA concentration due to a short event‐related stimulus. The change in GABA was simulated for both the ON and OFF subspectra, and the effect of three different conditions (increase only during ON acquisition, increase during OFF acquisition and increase across both) on the corresponding edited GABA spectrum was modelled. Results show that a transient increase in GABA that only occurs during the ON subspectral acquisition, while not changing the results much from when GABA is changed across both conditions, will give a much larger change in the edited GABA spectrum than a transient increase that occurs only during the OFF subspectral acquisition. These results suggest that researchers should think carefully about the design of any event‐related fMRS studies using MEGA‐PRESS, as well as the analysis of other functional paradigms where transient changes in GABA may be expected. Experimental design considerations are therefore discussed, and suggestions are made.
Proton magnetic resonance spectroscopy is a powerful tool to investigate neurochemistry and physiology in vivo. Recently researchers have started to use MRS to measure neurotransmitter changes ...related to neural activity, so called functional MRS (fMRS). Particular interest has been placed on measuring glutamate changes associated with neural function, but differences are reported in the size of changes seen. This review discusses fMRS, and includes meta‐analyses of the relative size of glutamate changes seen in fMRS, and the impact experimental design and stimulus paradigm may have. On average glutamate was found to increase by 6.97% (±1.739%) in response to neural activation. However, factors of experimental design may have a large impact on the size of these changes. For example an increase of 4.749% (±1.45%) is seen in block studies compared to an increase of 13.429% (±3.59) in studies using event related paradigms. The stimulus being investigated also seems to play a role with prolonged visual stimuli showing a small mean increase in glutamate of 2.318% (±1.227%) while at the other extreme, pain stimuli show a mean stimulation effect of 14.458% (±3.736%). These differences are discussed with regards to possible physiologic interpretations, as well experimental design implications.
With the advent of new analysis methods in neuroimaging that involve independent component analysis (ICA) and dynamic causal modelling (DCM), investigations have focused on measuring both the ...activity and connectivity of specific brain networks. In this study we combined DCM with spatial ICA to investigate network switching in the brain. Using time courses determined by ICA in our dynamic causal models, we focused on the dynamics of switching between the default mode network (DMN), the network which is active when the brain is not engaging in a specific task, and the central executive network (CEN), which is active when the brain is engaging in a task requiring attention. Previous work using Granger causality methods has shown that regions of the brain which respond to the degree of subjective salience of a stimulus, the salience network, are responsible for switching between the DMN and the CEN (Sridharan et al., 2008). In this work we apply DCM to ICA time courses representing these networks in resting state data. In order to test the repeatability of our work we applied this to two independent datasets. This work confirms that the salience network drives the switching between default mode and central executive networks and that our novel technique is repeatable.
•DCM and spatial ICA can be combined to study the connectivity between networks.•The result was replicated in two independent datasets, demonstrating repeatability.•Our result confirms previous work on the connectivity between networks.•This work has a lot of potential applications to ageing and patient data.•The technique can be easily applied to commonly acquired resting state data.
There is increasing interest in the use of edited proton magnetic resonance spectroscopy for the detection of GABA in the human brain. At a recent meeting held at Cardiff University, a number of ...spectroscopy groups met to discuss the acquisition, analysis and interpretation of GABA-edited MR spectra. This paper aims to set out the issues discussed at this meeting, reporting areas of consensus around parameters and procedures in the field and highlighting those areas where differences remain. It is hoped that this paper can fulfill two needs, providing a summary of the current ‘state-of-the-art’ in the field of GABA-edited MRS at 3T using MEGA-PRESS and a basic guide to help researchers new to the field to avoid some of the pitfalls inherent in the acquisition and processing of edited MRS for GABA.
► Report from a recent meeting of researchers using MEGA-PRESS for GABA ► Practicalities and issues of acquisition, processing and quantification discussed ► Provides a basis for standardization and validation in MEGA-PRESS applications ► Improving accessibility of the technique and interpretability of results
Frequency specific synchronisation of neuronal firing within the gamma-band (30–70Hz) appears to be a fundamental correlate of both basic sensory and higher cognitive processing. In-vitro studies ...suggest that the neurochemical basis of gamma-band oscillatory activity is based on interactions between excitatory (i.e. glutamate) and inhibitory (i.e. GABA) neurotransmitter concentrations. However, the nature of the relationship between excitatory neurotransmitter concentration and changes in gamma band activity in humans remains undetermined. Here, we examine the links between dynamic glutamate concentration and the formation of functional gamma-band oscillatory networks. Using concurrently acquired event-related magnetic resonance spectroscopy and electroencephalography, during a repetition-priming paradigm, we demonstrate an interaction between stimulus type (object vs. abstract pictures) and repetition in evoked gamma-band oscillatory activity, and find that glutamate levels within the lateral occipital cortex, differ in response to these distinct stimulus categories. Importantly, we show that dynamic glutamate levels are related to the amplitude of stimulus evoked gamma-band (but not to beta, alpha or theta or ERP) activity. These results highlight the specific connection between excitatory neurotransmitter concentration and amplitude of oscillatory response, providing a novel insight into the relationship between the neurochemical and neurophysiological processes underlying cognition.
•Evoked gamma-band activity changes in response to both object and abstract stimuli.•Glutamate levels in the LOC differ in response to distinct visual stimuli.•Glutamate levels correlate with concurrently measured gamma-band oscillatory power.•ER-MRS can quantify neurochemical concentration changes related to the EEG signal.
The discovery of liquid battery electrolytes that facilitate the formation of stable solid electrolyte interphases (SEIs) to mitigate dendrite formation is imperative to enable lithium anodes in ...next‐generation energy‐dense batteries. Compared to traditional electrolyte solvents, tetrahydrofuran (THF)‐based electrolyte systems have demonstrated great success in enabling high‐stability lithium anodes by encouraging the decomposition of anions (instead of organic solvent) and thus generating inorganic‐rich SEIs. Herein, by employing a variety of different lithium salts (i.e., LiPF6, LiTFSI, LiFSI, and LiDFOB), it is demonstrated that electrolyte anions modulate the inorganic composition and resulting properties of the SEI. Through novel analytical time‐of‐flight secondary‐ion mass spectrometry methods, such as hierarchical clustering of depth profiles and compositional analysis using integrated yields, the chemical composition and morphology of the SEIs generated from each electrolyte system are examined. Notably, the LiDFOB electrolyte provides an exceptionally stable system to enable lithium anodes, delivering >1500 cycles at a current density of 0.5 mAh g−1 and a capacity of 0.5 mAh g−1 in symmetrical cells. Furthermore, Li//LFP cells using this electrolyte demonstrate high‐rate, reversible lithium storage, supplying 139 mAh g(LFP)−1 at C/2 (≈0.991 mAh cm−2, @ 0.61 mA cm−2) with 87.5% capacity retention over 300 cycles (average Coulombic efficiency >99.86%).
Tetrahydrofuran‐based electrolyte systems have demonstrated success in enabling high‐stability lithium anodes by encouraging the decomposition of anions (instead of organic solvent) and thus generating inorganic‐rich solid electrolyte interphases (SEIs). By employing a variety of different lithium salts (i.e., LiPF6, LiTFSI, LiFSI, and LiDFOB), it is demonstrated that electrolyte anions can improve the inorganic composition and resulting properties of the SEI.
Sodium foil, promising for high‐energy‐density batteries, faces reversibility challenges due to its inherent reactivity and unstable solid electrolyte interphase (SEI) layer. In this study, a stable ...sodium metal battery (SMB) is achieved by tuning the electrolyte solvation structure through the addition of co‐solvent 2‐methyl tetrahydrofuran (MTHF) to diglyme (Dig). The introduction of cyclic ether‐based MTHF results in increased anion incorporation in the solvation structure, even at lower salt concentrations. Specifically, the anion stabilization capabilities of the environmentally sustainable MTHF co‐solvent lead to a contact‐ion pair‐based solvation structure. Time‐of‐flight mass spectroscopy analysis reveals that a shift toward an anion‐dominated solvation structure promotes the formation of a thin and uniform SEI layer. Consequently, employing a NaPF6‐based electrolyte with a Dig:MTHF ratio of 50% (v/v) binary solvent yields an average Coulombic efficiency of 99.72% for 300 cycles in Cu||Na cell cycling. Remarkably, at a C/2 cycling rate, Na||Na symmetric cell cycling demonstrates ultra‐long‐term stability exceeding 7000 h, and full cells with Na0.44MnO2 as a cathode retain 80% of their capacity after 500 cycles. This study systematically examines solvation structure, SEI layer composition, and electrochemical cycling, emphasizing the significance of MTHF‐based binary solvent mixtures for high‐performance SMBs.
In this study, introducing 2‐methyl tetrahydrofuran (MTHF) as a co‐solvent to diglyme (Dig) leads to a more anion‐dominated solvation structure even at low salt concentrations, thereby inducing a thin uniform solid electrolyte interphase (SEI) layer. The thin, robust SEI layer formed can promote long‐term stable electrochemical cycling of sodium metal anode, elucidating the critical role of anion stabilizing co‐solvents for stable sodium metal batteries.
Local changes in cerebral blood flow are thought to match changes in neuronal activity, a phenomenon termed neurovascular coupling. Hypoxia increases global resting cerebral blood flow, but regional ...cerebral blood flow (rCBF) changes are non-uniform. Hypoxia decreases baseline rCBF to the default mode network (DMN), which could reflect either decreased neuronal activity or altered neurovascular coupling. To distinguish between these hypotheses, we characterized the effects of hypoxia on baseline rCBF, task performance, and the hemodynamic (BOLD) response to task activity. During hypoxia, baseline CBF increased across most of the brain, but decreased in DMN regions. Performance on memory recall and motion detection tasks was not diminished, suggesting task-relevant neuronal activity was unaffected. Hypoxia reversed both positive and negative task-evoked BOLD responses in the DMN, suggesting hypoxia reverses neurovascular coupling in the DMN of healthy adults. The reversal of the BOLD response was specific to the DMN. Hypoxia produced modest increases in activations in the visual attention network (VAN) during the motion detection task, and had no effect on activations in the visual cortex during visual stimulation. This regional specificity may be particularly pertinent to clinical populations characterized by hypoxemia and may enhance understanding of regional specificity in neurodegenerative disease pathology.
Proton MR spectroscopy (1H-MRS) complements other brain research methods by providing measures of neurometabolites noninvasively in a localized brain area. Improvements in MR scanner technologies, ...and data acquisition and analysis methods should allow functional 1H-MRS (fMRS) to measure neurometabolite concentration changes during task-induced brain activation. The aim of the current study was to further develop event-related fMRS at 3T to investigate glutamate dynamics in response to repetition suppression. A secondary aim was to investigate the relationship between blood-oxygen-level-dependent (BOLD) responses and glutamate dynamics in the same paradigm at the same time. A novel approach of interleaved water-suppressed (metabolite) and unsuppressed (water) fMRS was used to simultaneously detect the event-related dynamics of glutamate and BOLD signal to repetition suppression in the lateral occipital cortex of thirteen (N=13) volunteers. On average, 1H-MRS-visible glutamate increased after novel visual stimuli presentations by 12% and decreased by 11–13% on repeated compared to novel presentations. The BOLD signal, as measured by water peak amplitude changes, showed significant difference between Task and Rest trials, and, on a GLM based analysis of the time series, demonstrated a significant difference between the novel and repeated trials, however appeared to be decoupled from the glutamate response as no correlation was found between the two. These results are the first demonstration that reductions in neuronal activity typical of repetition suppression effects are reflected by reduced glutamatergic and BOLD measures, that glutamate and BOLD responses may not be coupled as previously thought, and that these changes and relationships can be measured simultaneously using event-related fMRS at 3T.
•First event-related functional magnetic resonance study of repetition suppression•Simultaneous collection of BOLD signal and glutamate dynamics•Novel presentations of stimuli lead to increases in glutamate•Repetition of stimuli is associated with reductions in glutamate•BOLD measures associated with task are not correlated with glutamate changes
The translation of MRS to clinical practice has been impeded by the lack of technical standardization. There are multiple methods of acquisition, post‐processing, and analysis whose details greatly ...impact the interpretation of the results. These details are often not fully reported, making it difficult to assess MRS studies on a standardized basis. This hampers the reviewing of manuscripts, limits the reproducibility of study results, and complicates meta‐analysis of the literature. In this paper a consensus group of MRS experts provides minimum guidelines for the reporting of MRS methods and results, including the standardized description of MRS hardware, data acquisition, analysis, and quality assessment. This consensus statement describes each of these requirements in detail and includes a checklist to assist authors and journal reviewers and to provide a practical way for journal editors to ensure that MRS studies are reported in full.
This paper sets out the expert consensus on minimum reporting guidelines for MRS studies. It includes a checklist as a practical way for authors and journal editors to ensure that MRS studies are reported appropriately. A common set of reporting standards will greatly increase transparency, rigor, and replicability of MRS studies, and should further the successful integration of MRS into widespread clinical practice.
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