Metabolite concentration changes associated with positive and negative BOLD responses in the human visual cortex: A functional MRS study at 7 Tesla

Boillat, Yohan; Xin, Lijing; Zwaag, Wietske van der; Gruetter, Rolf

doi:10.1177/0271678x19831022

Cited by 46 publications

(62 citation statements)

References 94 publications

(117 reference statements)

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“…Our results are in line with recent findings showing that the average concentration of GABA during high contrast checkerboard stimulation was no different from a resting baseline (Kurcyus et al, 2018). Decreases in GABA with functional stimulation have been shown in the motor cortex using a sustained task (10 min hand clenching) and a GABA-edited sequence (Chen et al, 2017), whereas another study has found decreases in GABA in the visual cortex corresponding to a region of sustained negative BOLD response (Boillat et al, 2019). As GABAergic neurons represent 15%-30% of the total population (DeFelipe and Fariñas, 1992), sustained stimulation (Chen et al, 2017) and edited MRS sequences optimized for GABA, such as MEGA-PRESS (Mescher et al, 1998;Mullins et al, 2014), may be necessary to improve sensitivity to modulation of inhibitory activity in the early visual cortex.…”

Section: Discussionsupporting

confidence: 93%

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Comparison of Neurochemical and BOLD Signal Contrast Response Functions in the Human Visual Cortex

Emir

Parker

et al. 2019

J. Neurosci.

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We investigated the relationship between neurochemical and hemodynamic responses as a function of image contrast in the human primary visual cortex (V1). Simultaneously acquired BOLD-fMRI and single voxel proton MR spectroscopy signals were measured in V1 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.

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Section: Discussionsupporting

confidence: 93%

“…For lower image contrasts, glutamate is below baseline, although not significantly so. These changes are unlikely due to negative BOLD signal (Boillat et al, 2019), as BOLD responses were significantly higher than baseline at all contrast levels (Fig. 4A).…”

Section: Discussionmentioning

confidence: 90%

Comparison of Neurochemical and BOLD Signal Contrast Response Functions in the Human Visual Cortex

Emir

Parker

et al. 2019

J. Neurosci.

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“…We showed that an extensive number of brain metabolites can be measured non-invasively in the human brain at ultra-high magnetic field of 7 T (Tkáč et al, 2001). We subsequently demonstrated that changes in neural activity are associated with relatively small changes in several metabolite concentrations which could be reliably detected at 7 T (Mangia et al, 2007a, b; Bednařík et al, 2015, 2018), as confirmed by other labs (Lin et al, 2012; Schaller et al, 2013, 2014; Boillat et al, 2019). The capability to measure these functional changes provides unique insights into how brain metabolism is associated with neural activity (Mangia et al, 2009).…”

Section: Introductionsupporting

confidence: 75%

Influence of Repetitive Transcranial Magnetic Stimulation on Human Neurochemistry and Functional Connectivity: A Pilot MRI/MRS Study at 7 T

et al. 2019

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Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive brain stimulation method commonly used in the disciplines of neuroscience, neurology, and neuropsychiatry to examine or modulate brain function. Low frequency rTMS (e.g., 1 Hz) is associated with a net suppression of cortical excitability, whereas higher frequencies (e.g., 5 Hz) purportedly increase excitability. Magnetic resonance spectroscopy (MRS) and resting-state functional MRI (rsfMRI) allow investigation of neurochemistry and functional connectivity, respectively, and can assess the influence of rTMS in these domains. This pilot study investigated the effects of rTMS on the primary motor cortex using pre and post MRS and rsfMRI assessments at 7 T. Seven right-handed males (age 27 ± 7 y.o.) underwent single-voxel MRS and rsfMRI before and about 30-min after rTMS was administered outside the scanner for 20-min over the primary motor cortex of the left (dominant) hemisphere. All participants received 1-Hz rTMS; one participant additionally received 5-Hz rTMS in a separate session. Concentrations of 17 neurochemicals were quantified in left and right motor cortices. Connectivity metrics included fractional amplitude of low-frequency fluctuations (fALFF) and regional homogeneity (ReHo) of both motor cortices, strength of related brain networks, and inter-hemispheric connectivity. The group-analysis revealed few trends (i.e., uncorrected for multiple comparisons), including a mean increase in the concentration of the inhibitory neurotransmitter γ-aminobutyric acid (GABA) after the inhibitory rTMS protocol as compared to baseline in the stimulated (left) motor cortex (+8%, p = 0.043), along with a slight increase of total creatine (+2%, p = 0.018), and decrease of aspartate (−18%, p = 0.016). Additionally, GABA tended to decrease in the contralateral hemisphere (−6%, p = 0.033). No other changes of metabolite concentrations were found. Whereas functional connectivity outcomes did not exhibit trends of significant changes induced by rTMS, the percent changes of few connectivity metrics in both hemispheres were negatively correlated with GABA changes in the contralateral hemisphere. While studies in larger cohorts are needed to confirm these preliminary findings, our results indicate the safety and feasibility of detecting changes in key metabolites associated with neurotransmission after a single 1-Hz rTMS session, establishing the construct for future exploration of the neurochemical, and connectivity mechanisms of cortical responses to neuromodulation.

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“…There is a large body of evidence from fMRI studies that DMN is implicated in various brain diseases. 1 We suggest that applied task distinguishes the definition of task-positive and task-negative brain areas, such as VC could be activated by whole-screen flashing checkerboard 3–5 as well as deactivated by small flashing checkerboard 3,6 and visual-spatial attention. 7,8…”

Section: Introductionmentioning

confidence: 99%

Metabolic underpinnings of activated and deactivated cortical areas in human brain

Koush

Graaf

Kupers

et al. 2021

J Cereb Blood Flow Metab

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Neuroimaging with functional MRI (fMRI) identifies activated and deactivated brain regions in task-based paradigms. These patterns of (de)activation are altered in diseases, motivating research to understand their underlying biochemical/biophysical mechanisms. Essentially, it remains unknown how aerobic metabolism of glucose to lactate (aerobic glycolysis) and excitatory-inhibitory balance of glutamatergic and GABAergic neuronal activities vary in these areas. In healthy volunteers, we investigated metabolic distinctions of activating visual cortex (VC, a task-positive area) using a visual task and deactivating posterior cingulate cortex (PCC, a task-negative area) using a cognitive task. We used fMRI-guided J-edited functional MRS (fMRS) to measure lactate, glutamate plus glutamine (Glx) and γ-aminobutyric acid (GABA), as indicators of aerobic glycolysis and excitatory-inhibitory balance, respectively. Both lactate and Glx increased upon activating VC, but did not change upon deactivating PCC. Basal GABA was negatively correlated with BOLD responses in both brain areas, but during functional tasks GABA decreased in VC upon activation and GABA increased in PCC upon deactivation, suggesting BOLD responses in relation to baseline are impacted oppositely by task-induced inhibition. In summary, opposite relations between BOLD response and GABAergic inhibition, and increases in aerobic glycolysis and glutamatergic activity distinguish the BOLD response in (de)activated areas.

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Metabolite concentration changes associated with positive and negative BOLD responses in the human visual cortex: A functional MRS study at 7 Tesla

Cited by 46 publications

References 94 publications

Comparison of Neurochemical and BOLD Signal Contrast Response Functions in the Human Visual Cortex

Comparison of Neurochemical and BOLD Signal Contrast Response Functions in the Human Visual Cortex

Influence of Repetitive Transcranial Magnetic Stimulation on Human Neurochemistry and Functional Connectivity: A Pilot MRI/MRS Study at 7 T

Metabolic underpinnings of activated and deactivated cortical areas in human brain

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