Anesthesia differentially modulates neuronal and vascular contributions to the BOLD signal

Alst, Timo Mauritz van; Wachsmuth, Lydia; Datunashvili, Maia; Albers, Franziska; Just, Nathalie; Budde, Thomas; Faber, Cornelius

doi:10.1016/j.neuroimage.2019.03.057

Cited by 42 publications

(45 citation statements)

References 83 publications

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“…After carefully positioning the rat in the scanner with the brain in the center of the volume coil, and acquiring pilot and anatomical images [rapid imaging with refocused echoes (RARE) T 2 -weighted, TR/TE = 4000/12.5 ms; RARE factor = 8; FOV = 28 9 26 mm 2 ; Matrix = 256 9 256; slice thickness = 0.8 mm; 16 slices], anesthesia was switched to medetomidine (Domitor; Pfizer, Orion Corporation, Espoo, Finland, 2016) (0.04 mg/kg (bolus) + 0.05 mg/kg/h (subcutaneous infusion)) and isoflurane was discontinued. This switch in anesthesia allows the observation of functional brain activity under light sedation in the rat or mouse brain and is widely used nowadays to perform BOLD-fMRI studies (Seuwen et al 2015;Schwalm et al 2017;van Alst et al 2019).…”

Section: Bold-fmrimentioning

confidence: 99%

Probing activation‐induced neurochemical changes using optogenetics combined with functional magnetic resonance spectroscopy: a feasibility study in the rat primary somatosensory cortex

Just

Faber

2019

Journal of Neurochemistry

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Knowledge about biochemical processes is a prerequisite for a better understanding of mechanisms underlying brain activity. 1H functional magnetic resonance spectroscopy (1H‐fMRS) at high magnetic fields allows for the non‐invasive measurement of metabolic changes during brain activation. Optogenetics, on the other hand, has revolutionized the field of neuroscience. It was previously coupled with functional magnetic resonance imaging (fMRI) techniques in rodents enabling population‐specific targeting of cells, investigating brain networks with unprecedented in vivo precision. The coupling of optogenetics and 1H‐fMRS is expected to enhance the specificity of metabolic readouts to validate neuro‐energetic theories underlying brain activity. To date, the feasibility of combining optogenetic stimulation with fMRS has not been explored. We used green laser stimulation delivered through an optical fiber implanted superficially above the primary somatosensory forelimb cortex (S1FL) of rats expressing the C1V1 opsin in excitatory neurons. A protocol for the acquisition of functional 1H MR spectra upon optogenetic stimulation without craniotomy‐induced artefacts was established. Quantification of metabolite concentrations in S1FL upon optogenetic and electrical forepaw stimulation demonstrated significantly increased glutamate levels (+8.8% and +9.9%, p < 0.05 respectively), which were compensated by decreased glutamine levels (−17% and −18%, p < 0.05 respectively). Our results demonstrate for the first time the feasibility of combining optogenetic control and functional MR spectroscopy (o‐fMRS) in the rat somatosensory cortex, opening new possibilities for monitoring the energetic demands of specific cell populations and for exploring the underpinnings of energy metabolism during brain activity. Open Science Badges This article has received a badge for *Open Materials* because it provided all relevant information to reproduce the study in the manuscript. The complete Open Science Disclosure form for this article can be found at the end of the article. More information about the Open Practices badges can be found at https://cos.io/our-services/open-science-badges/.

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Section: Bold-fmrimentioning

confidence: 99%

Probing activation‐induced neurochemical changes using optogenetics combined with functional magnetic resonance spectroscopy: a feasibility study in the rat primary somatosensory cortex

Just

Faber

2019

Journal of Neurochemistry

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“…Proper interpretation of the BOLD signal when using anaesthesia is further complicated by variability in vasodilation caused by different levels of anaesthesia, the use of different anaesthetics across studies [170] and different responses to anaesthesia across species. To separate the neural and vascular effects of anaesthesia on the BOLD signal, parallel acquisition of fMRI and calcium imaging can be implemented [81], highlighting how both the effect of anaesthetics and CO 2 on the BOLD signal must be considered [178]. Despite these confounding effects, anaesthetic protocols are being identified that deliver long-lasting sedation with robust and time-invariant stimulus-evoked BOLD responses.…”

Section: Cross-species Magnetic Resonance Imagingmentioning

confidence: 99%

Cross-species neuroscience: closing the explanatory gap

Barron

Mars

Dupret

et al. 2020

Phil. Trans. R. Soc. B

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Neuroscience has seen substantial development in non-invasive methods available for investigating the living human brain. However, these tools are limited to coarse macroscopic measures of neural activity that aggregate the diverse responses of thousands of cells. To access neural activity at the cellular and circuit level, researchers instead rely on invasive recordings in animals. Recent advances in invasive methods now permit large-scale recording and circuit-level manipulations with exquisite spatio-temporal precision. Yet, there has been limited progress in relating these microcircuit measures to complex cognition and behaviour observed in humans. Contemporary neuroscience thus faces an explanatory gap between macroscopic descriptions of the human brain and microscopic descriptions in animal models. To close the explanatory gap, we propose adopting a cross-species approach. Despite dramatic differences in the size of mammalian brains, this approach is broadly justified by preserved homology. Here, we outline a three-armed approach for effective cross-species investigation that highlights the need to translate different measures of neural activity into a common space. We discuss how a cross-species approach has the potential to transform basic neuroscience while also benefiting neuropsychiatric drug development where clinical translation has, to date, seen minimal success. This article is part of the theme issue ‘Key relationships between non-invasive functional neuroimaging and the underlying neuronal activity’.

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“…Inhaled gas remains one of the standard anesthesia in preclinical MRI studies for its ease of use (intubation is not a necessity and no canulation is required) and fexibility in dosage. However, in rodent BOLD fMRI studies, ISO anesthesia demonstrated many disadvantages compared to other anesthetics (i.e medetomidine) as BOLD responses disappear due to inherent vasodilatatory effects and increasing CO2 levels in non-ventilated animals (Reimann H et al, 2020 ;van Alst et al, 2019). In sheep, the effects of anesthesia for preclinical MRI studies has not been investigated to the best of our knowledge.…”

Section: Impact Of Isoflurane Anesthesia On Bold Fmri Responses In Sheepmentioning

confidence: 99%

“…Lately, there have also been increased interest for a better understanding of the impact of anaesthesia in fMRI preclinical rodent studies (van Alst et al, 2019;Reimann and Niendorf, 2020;Just et al, 2020). Inhaled anaesthetics (isoflurane (ISO), sevoflurane …) in intubated and non-intubated animals remain the most standard type of anaesthesia although many recent reports show dissociation of Blood Oxygen Level dependent (BOLD) and neural responses above 1.2 % ISO anaesthesia (Sonnay et al, 2018;van Alst et al, 2019). The impact of inhaled anaesthetics has been less studied in larger animals.…”

Section: Introductionmentioning

confidence: 99%

The sheep brain: an interesting translational model for functional MRI studies?

Just

Adriaensen

Chevillard

et al. 2020

Preprint

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Biomedical investigations in clinically relevant animal models is of crucial interest for faster and appropriate transfer to human. The ovine model has already demonstrated its potential compared to rodents and non-human primates (NHP) in various studies: sheep possess a gyrencephalic brain, captivity is not an issue and can undergo magnetic resonance imaging (MRI) in routine clinical scanners (1.5T, 3T) under identical conditions using similar techniques to humans. To date, the effects of anesthesia have been poorly explored and only few functional MRI (fMRI) studies were conducted in sheep. Here, Blood Oxygen Level dependent fMRI and perfusion MRI were conducted in lambs and adult ewes at 3 T. Robust but weak BOLD responses to visual stimulation were found in the lateral geniculate nucleus (LGN) up to 3% isoflurane anaesthesia. BOLD responses were weaker in adult sheep than in lambs while relative cerebral blood volumes (rCBV) and relative cerebral blood flows (rCBF) were significantly higher in lambs than in adult sheep for both gray and white matter in accordance with previous findings in the human. Assessment of functional responses in healthy individuals under adequate physiological conditions is essential for robust translational studies.

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Anesthesia differentially modulates neuronal and vascular contributions to the BOLD signal

Cited by 42 publications

References 83 publications

Probing activation‐induced neurochemical changes using optogenetics combined with functional magnetic resonance spectroscopy: a feasibility study in the rat primary somatosensory cortex

Probing activation‐induced neurochemical changes using optogenetics combined with functional magnetic resonance spectroscopy: a feasibility study in the rat primary somatosensory cortex

Cross-species neuroscience: closing the explanatory gap

The sheep brain: an interesting translational model for functional MRI studies?

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