Event-related dynamics of glutamate and BOLD effects measured using functional magnetic resonance spectroscopy (fMRS) at 3 T in a repetition suppression paradigm

Apšvalka, Dace; Gadie, Andrew; Clemence, M; Mullins, Paul G.

doi:10.1016/j.neuroimage.2015.06.015

Cited by 81 publications

(129 citation statements)

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“…Future fMRS studies could take these design considerations into account, and aim for shorter block lengths, as presented in this study, to achieve maximal continuity with related functional measures. Other alternatives to maintain the amplitude of the BOLD-response include inserting short inter-stimulus-intervals between presentations (Sonnay et al, 2015), or using event-related presentation paradigms (Apsvalka et al, 2015). We have demonstrated that our scanning procedure allowed us to capture changes in glutamate at 64 s, a time scale suitable for functional MRI studies.…”

Section: Discussionmentioning

confidence: 99%

“…1 H-MRS is a non-invasive measure of absolute concentrations of neurochemicals and, particularly in the absence of any sensory stimulation, has been exploited to identify biomarkers of normal and pathological brain states (Oz et al, 2014). While several recent studies have measured functional 1 H-MRS during specific tasks (Mangia et al, 2006, Mangia et al, 2007, Lin et al, 2012, Schaller et al, 2013, Schaller et al, 2014, Apsvalka et al, 2015, Bednarik et al, 2015), no study to date has quantified simultaneous changes in neurochemicals and brain activity using BOLD-fMRI. Here, we provide the first demonstration of combined fMRI-MRS measurements, and reveal a specific relationship between changes in BOLD-fMRI and glutamate at time scales relevant to conventional fMRI block design experiments (64 s).…”

Section: Introductionmentioning

confidence: 99%

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Combined fMRI-MRS acquires simultaneous glutamate and BOLD-fMRI signals in the human brain

et al. 2017

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Combined fMRI-MRS is a novel method to non-invasively investigate functional activation in the human brain using simultaneous acquisition of hemodynamic and neurochemical measures. The aim of the current study was to quantify neural activity using combined fMRI-MRS at 7 T. BOLD-fMRI and semi-LASER localization MRS data were acquired from the visual cortex of 13 participants during short blocks (64 s) of flickering checkerboards. We demonstrate a correlation between glutamate and BOLD-fMRI time courses (R=0.381, p=0.031). In addition, we show increases in BOLD-fMRI (1.43±0.17%) and glutamate concentrations (0.15±0.05 I.U., ~2%) during visual stimulation. In contrast, we observed no change in glutamate concentrations in resting state MRS data during sham stimulation periods. Spectral line width changes generated by the BOLD-response were corrected using line broadening. In summary, our results establish the feasibility of concurrent measurements of BOLD-fMRI and neurochemicals using a novel combined fMRI-MRS sequence. Our findings strengthen the link between glutamate and functional activity in the human brain by demonstrating a significant correlation of BOLD-fMRI and glutamate over time, and by showing ~2% glutamate increases during 64 s of visual stimulation. Our tool may become useful for studies characterizing functional dynamics between neurochemicals and hemodynamics in health and disease.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Combined fMRI-MRS acquires simultaneous glutamate and BOLD-fMRI signals in the human brain

et al. 2017

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“…13 C-MRS, though technically demanding and yet to be widely applied in large human samples, could in future studies assess more directly glutamate and glutamine metabolic cycling and their relationship to glutamate-related risk genes in schizophrenia. Third, Glx measurements were acquired without controlling for cognitive state, which can affect glutamate levels (26). Fourth, schizophrenia subjects were treated with antipsychotic medications, agents known to affect brain glutamate levels (2).…”

Section: Discussionmentioning

confidence: 99%

Risk-Conferring Glutamatergic Genes and Brain Glutamate Plus Glutamine in Schizophrenia

et al. 2017

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BackgroundThe proton magnetic resonance spectroscopy (1H-MRS) signals from glutamate (or the combined glutamate and glutamine signal—Glx) have been found to be greater in various brain regions in people with schizophrenia. Recently, the Psychiatric Genetics Consortium reported that several common single-nucleotide polymorphisms (SNPs) in glutamate-related genes confer increased risk of schizophrenia. Here, we examined the relationship between presence of these risk polymorphisms and brain Glx levels in schizophrenia.Methods1H-MRS imaging data from an axial, supraventricular tissue slab were acquired in 56 schizophrenia patients and 67 healthy subjects. Glx was measured in gray matter (GM) and white matter (WM) regions. The genetic data included six polymorphisms genotyped across an Illumina 5M SNP array. Only three of six glutamate as well as calcium-related SNPs were available for examination. These included three glutamate-related polymorphisms (rs10520163 in CLCN3, rs12704290 in GRM3, and rs12325245 in SLC38A7), and three calcium signaling polymorphisms (rs1339227 in RIMS1, rs7893279 in CACNB2, and rs2007044 in CACNA1C). Summary risk scores for the three glutamate and the three calcium polymorphisms were calculated.ResultsGlx levels in GM positively correlated with glutamate-related genetic risk score but only in younger (≤36 years) schizophrenia patients (p = 0.01). Glx levels did not correlate with calcium risk scores. Glx was higher in the schizophrenia group compared to levels in controls in GM and WM regardless of age (p < 0.001).ConclusionElevations in brain Glx are in part, related to common allelic variants of glutamate-related genes known to increase the risk for schizophrenia. Since the glutamate risk scores did not differ between groups, some other genetic or environmental factors likely interact with the variability in glutamate-related risk SNPs to contribute to an increase in brain Glx early in the illness.

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“…In addition, in the same study, BOLD‐fMRI signals were positively correlated with Glu and Lac concentration changes and inversely correlated with the baseline (resting) concentration of the neurotransmitter γ‐aminobutyric acid (GABA). However, BOLD signals were not found to be correlated with the Glu response when studying event‐related dynamics of Glu and BOLD effects in another fMRS study using a repetition suppression paradigm at 3 T . Finally, short‐TE sequences were used at 7 T 20 ,21 and 3 T 22 to investigate neurotransmitter changes in the anterior cingulate cortex in response to a Stroop task.…”

Section: Introductionmentioning

confidence: 99%

Detection of metabolite changes in response to a varying visual stimulation paradigm using short‐TE ¹H MRS at 7 T

et al. 2016

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The two-fold benefit of H magnetic resonance spectroscopy (MRS) at high B fields - enhanced sensitivity and increased spectral dispersion - has been used previously to study dynamic changes in metabolite concentrations in the human brain in response to visual stimulation. In these studies, a strong visual on/off stimulus was combined with MRS data acquisition in a voxel location in the occipital cortex determined by an initial functional magnetic resonance imaging experiment. However, 1) to exclude the possibility of systemic effects (heartbeat, blood flow, etc.), which tend to be different for on/off conditions, a modified stimulation condition not affecting the target voxel needs to be employed, and 2) to assess important neurotransmitters of low concentration, in particular γ-aminobutyric acid (GABA), it may be advantageous to analyze steady-state, rather than dynamic, conditions. Thus, the aim of this study was to use short-TE H MRS methodology at 7 T to detect differences in steady-state metabolite levels in response to a varying stimulation paradigm in the human visual cortex. The two different stimulation conditions were termed voxel and control activation. Localized MR spectra were acquired using the SPECIAL (spin-echo full-intensity acquired localized) sequence. Data were analyzed using LCModel. Fifteen individual metabolites were reliably quantified. On comparison of steady-state concentrations for voxel versus control activation, a decrease in GABA of 0.05 mmol/L (5%) and an increase in lactate of 0.04 mmol/L (7%) were found to be the only significant effects. The observed reduction in GABA can be interpreted as reduced neuronal inhibition during voxel activation, whereas the increase in lactate hints at an intensification of anaerobic glycolysis. Differences from previous studies, notably the absence of any changes in glutamate, are attributed to the modified experimental conditions. This study demonstrates that the use of advanced H MRS methodology at 7 T allows the detection of subtle changes in metabolite concentrations involved in neuronal activation and inhibition.

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Event-related dynamics of glutamate and BOLD effects measured using functional magnetic resonance spectroscopy (fMRS) at 3 T in a repetition suppression paradigm

Cited by 81 publications

References 42 publications

Combined fMRI-MRS acquires simultaneous glutamate and BOLD-fMRI signals in the human brain

Combined fMRI-MRS acquires simultaneous glutamate and BOLD-fMRI signals in the human brain

Risk-Conferring Glutamatergic Genes and Brain Glutamate Plus Glutamine in Schizophrenia

Detection of metabolite changes in response to a varying visual stimulation paradigm using short‐TE ¹H MRS at 7 T

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Event-related dynamics of glutamate and BOLD effects measured using functional magnetic resonance spectroscopy (fMRS) at 3 T in a repetition suppression paradigm

Cited by 81 publications

References 42 publications

Combined fMRI-MRS acquires simultaneous glutamate and BOLD-fMRI signals in the human brain

Combined fMRI-MRS acquires simultaneous glutamate and BOLD-fMRI signals in the human brain

Risk-Conferring Glutamatergic Genes and Brain Glutamate Plus Glutamine in Schizophrenia

Detection of metabolite changes in response to a varying visual stimulation paradigm using short‐TE 1H MRS at 7 T

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Detection of metabolite changes in response to a varying visual stimulation paradigm using short‐TE ¹H MRS at 7 T