Metabolic changes assessed by MRS accurately reflect brain function during drug-induced epilepsy in mice in contrast to fMRI-based hemodynamic readouts

Seuwen, Aline; Schroeter, Aileen; Grandjean, Joanes; Rudin, Markus

doi:10.1016/j.neuroimage.2015.07.004

Cited by 12 publications

(21 citation statements)

References 34 publications

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“…The shape and size of RTN make this important nucleus very difficult to avoid. Other techniques such as proton MR spectroscopic imaging (MRSI) (Seuwen et al, 2015 ) may be more adequate for future investigations while fMRS techniques coupled to optogenetic stimulation may help unraveling the exact contribution of this structure (Jurgens et al, 2012 ).…”

Section: Discussionmentioning

confidence: 99%

“…One of the main pitfalls of the present study was its sequential design that unfortunately did not allow simultaneous assessment of BOLD, thalamic and S1BF metabolites. Using magnetic MRSI techniques such as FIDLOVs (Seuwen et al, 2015 ) which would at the same time contribute to preserve SNR levels and time may help while there is definitely a need for increased targeting at smaller structures with higher SNR levels for an increased specificity of studies as mentioned earlier for RTN or in pathologies (Pan et al, 2015 ). Finally, BOLD responses may be measured directly from fMRS acquisitions using changes in linewidths of NAA or total Creatine peaks as a result of activation which would also decrease scanning time.…”

Section: Limitations and Perspectivesmentioning

confidence: 99%

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Investigating the Role of Glutamate and GABA in the Modulation of Transthalamic Activity: A Combined fMRI-fMRS Study

Just

Sonnay

2017

Front. Physiol.

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The Excitatory-Inhibitory balance (EIB) between glutamatergic and GABAergic neurons is known to regulate the function of thalamocortical neurocircuits. The thalamus is known as an important relay for glutamatergic and GABAergic signals ascending/descending to/from the somatosensory cortex in rodents. However, new investigations attribute a larger role to thalamic nuclei as modulators of information processing within the cortex. In this study, functional Magnetic Resonance Spectroscopy (fMRS) was used to measure glutamate (Glu) and GABA associations with BOLD responses during activation of the thalamus to barrel cortex (S1BF) pathway at 9.4T. In line with previous studies in humans, resting GABA and Glu correlated negatively and positively respectively with BOLD responses in S1BF. Moreover, a significant negative correlation (R = −0.68, p = 0.0024) between BOLD responses in the thalamus and the barrel cortex was found. Rats with low Glu levels and high resting GABA levels in S1BF demonstrated lower BOLD responses in S1BF and high amplitude BOLD responses in the thalamus themselves linked to the release of high GABA levels during stimulation. In addition, early analysis of resting state functional connectivity suggested EIB controlled thalamocortical neuronal synchrony. We propose that the presented approach may be useful for further characterization of diseases affecting thalamocortical neurotransmission.

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Section: Discussionmentioning

confidence: 99%

Section: Limitations and Perspectivesmentioning

confidence: 99%

Investigating the Role of Glutamate and GABA in the Modulation of Transthalamic Activity: A Combined fMRI-fMRS Study

Just

Sonnay

2017

Front. Physiol.

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“…Previously, we proposed a 1 H-MRS approach based on spectroscopic imaging (SI) for mapping metabolite and neurotransmitter distribution in the mouse brain at 1 µl nominal spatial and 12 min temporal resolution 23 . MRSI allows covering significant brain area, thereby enabling the comparison of stimuli-induced changes in metabolite profiles in responsive and non-responsive brain areas.…”

Section: Introductionmentioning

confidence: 99%

“…The MRSI approach proposed is based on the acquisition of the free induction decay (FID) signal and thus provides increased signal intensity and minimal chemical shift displacement artifacts 24 as compared to spin-echo based data acquisition, and therefore constitutes an attractive alternative to SVS for functional measurements in mice. We have used the method earlier to quantify dose-dependent changes in levels of neurotransmitters and metabolites involved in energy metabolism in response to GABA A receptor inhibition in a region-dependent manner 23 . In the present study, we have applied the MRSI approach to assess regional Glu changes in response to sensory input, i.e.…”

Section: Introductionmentioning

confidence: 99%

Functional spectroscopic imaging reveals specificity of glutamate response in mouse brain to peripheral sensory stimulation

Seuwen

Schroeter

Grandjean

et al. 2019

Sci Rep

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Non-invasive investigation of physiological changes and metabolic events associated with brain activity in mice constitutes a major challenge. Conventionally, fMRI assesses neuronal activity by evaluating activity-evoked local changes in blood oxygenation levels (BOLD). In isoflurane-anaethetized mice, however, we found that BOLD signal changes during paw stimulation appear to be dominated by arousal responses even when using innocuous stimuli. Widespread responses involving both hemispheres have been observed in response to unilateral stimulation. MRS allows probing metabolic changes associated with neuronal activation and provides a complementary readout to BOLD fMRI for investigating brain activity. In this study we evaluated the sensitivity of a free induction decay (FID) based spectroscopic imaging (MRSI) protocol for the measurement of alterations in glutamate levels elicited by unilateral electrical paw stimulation at different current amplitudes. Coronal MRSI maps of glutamate distribution with 17 × 17 voxels of 1 µl volume have been recorded with a temporal resolution of 12 min. Significant region-specific increases in glutamate levels have been observed in the contralateral but not in the ispiateral S1 somatosensory cortex upon stimulation. The amplitude of glutamate changes increased in a dose-dependent manner with the stimulus amplitude. The study demonstrates feasibility of functional MRSI in mice for studying activity-evoked glutamate changes in a temporo-spatially resolved manner.

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“…GluCEST imaging can map the level of glutamate in vivo at a high spatial resolution ( 9 – 11 ), and diffusion tensor imaging is used to reveal the in vivo connectivity of the nervous system ( 12 , 13 ). 1 H-MRS allows noninvasive quantification of brain metabolites in specific brain areas and has been successfully used in the field of epilepsy research ( 14 , 15 ). Specifically, the in vivo developmental changes in neurometabolites and connectivity were measured in the cingulate cortex, which has extensive connections with critical regions such as the basal ganglia, thalamus, brainstem, and hippocampus ( 16 , 17 ).…”

Section: Introductionmentioning

confidence: 99%

In Vivo Multimodal Magnetic Resonance Imaging Changes After N-Methyl-d-Aspartate-Triggered Spasms in Infant Rats

et al. 2018

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ObjectiveDespite the serious neurodevelopmental sequelae of epileptic encephalopathy during infancy, the pathomechanisms involved remain unclear. To find potential biomarkers that can reflect the pathogenesis of epileptic encephalopathy, we explored the neurometabolic and microstructural sequelae after infantile spasms using a rat model of infantile spasms and in vivo magnetic resonance imaging techniques.MethodsRats prenatally exposed to betamethasone were subjected to three rounds of intraperitoneal N-methyl-d-aspartate (NMDA) triggering of spasms or received saline injections (controls) on postnatal days (P) 12, 13, and 15. Chemical exchange saturation transfer imaging of glutamate (GluCEST) were performed at P15 and 22 and diffusion tensor imaging and additional spectroscopy (1H-MRI/MRS) of the cingulate cortex were serially done at P16, 23, and 30 and analyzed. Pathological analysis and western blotting were performed with rats sacrificed on P35.ResultsWithin 24 h of the three rounds of NMDA-induced spasms, there was an acute increase in the GluCEST (%) in the cortex, hippocampus, and striatum. When focused on the cingulate cortex, mean diffusivity (MD) was significantly decreased during the acute period after multiple spasms with an increase in γ-aminobutyric acid (GABA), glutamate, and glutamine N-acetylaspartate-plus-N-acetylaspartylglutamate (tNAA), total choline, and total creatine. The juvenile rats also showed decreased MD on diffusion tensor imaging and significant decreases in taurine, tNAA, and macromolecules-plus-lipids in the cingulate cortex. Pathologically, there was a significant reduction in glial fibrillary acidic protein, myelin basic protein, and neuronal nuclei expression in the cingulate cortex of rats with NMDA-induced spasms.SignificanceThese neurometabolic and microstructural alterations after NMDA-triggered spasms might be potential imaging biomarkers of epileptic encephalopathy.

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Metabolic changes assessed by MRS accurately reflect brain function during drug-induced epilepsy in mice in contrast to fMRI-based hemodynamic readouts

Cited by 12 publications

References 34 publications

Investigating the Role of Glutamate and GABA in the Modulation of Transthalamic Activity: A Combined fMRI-fMRS Study

Investigating the Role of Glutamate and GABA in the Modulation of Transthalamic Activity: A Combined fMRI-fMRS Study

Functional spectroscopic imaging reveals specificity of glutamate response in mouse brain to peripheral sensory stimulation

In Vivo Multimodal Magnetic Resonance Imaging Changes After N-Methyl-d-Aspartate-Triggered Spasms in Infant Rats

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