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

Ip, Betina; Emir, Uzay E.; Parker, Andrew; Campbell, Jon; Bridge, Holly

doi:10.1523/jneurosci.3021-18.2019

Cited by 45 publications

(57 citation statements)

References 56 publications

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“…This sensory stimulation is likely to cause functional changes in the dynamics of neurometabolism in the cortex. While these stimuli-driven fluctuations could be detected in high-field functional MRS, as shown in recent studies Ip, Emir, Parker, Campbell, & Bridge, 2019], the evidence for such changes effecting MRS measures collected in 3T is limited, and the size of these effects is small [Apšvalka et al, 2015;Kurcyus et al, 2018]. Hence, we believe that while the movies introduce a certain amount of noise to our measurements, the benefit of increasing subject compliance, which is critical for achieving high-quality data (i.e., by reducing head motion and facilitating completion of a long scanning session), is greater than the cost, particularly in the case of group comparisons.…”

Section: Discussionmentioning

confidence: 54%

“…However, the current findings do not preclude the role of disrupted neurotransmission in the disorder nor the potential benefit from pharmacological manipulation of the GABAergic and glutamatergic systems. While MRS might not be suitable for detecting baseline differences in GABA or glutamate, it has been shown to track changes in neurometabolite levels following pharmacological manipulation in both rats [Waschkies et al, 2014] and humans [Ajram et al, 2017;Pretzsch et al, 2019;Zhang et al, 2020], as well as changes in metabolite levels in response to sensory stimuli [Apšvalka et al, 2015;Ip et al, 2019;Kurcyus et al, 2018]. Future studies using such causal manipulations of neurotransmitter levels with MRS may provide greater clarity regarding their potential role in the pathophysiology of ASD.…”

Section: Discussionmentioning

confidence: 99%

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Concentrations of Cortical GABA and Glutamate in Young Adults With Autism Spectrum Disorder

et al. 2020

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The balance of excitation and inhibition in neural circuits is hypothesized to be increased in autism spectrum disorder, possibly mediated by altered signaling of the inhibitory neurotransmitter γaminobutyric acid (GABA), yet empirical evidence in humans is inconsistent. We used edited magnetic resonance spectroscopy (MRS) to quantify signals associated with both GABA and the excitatory neurotransmitter glutamate in multiple regions of the sensory and sensorimotor cortex, including primary visual, auditory, and motor areas in adult individuals with autism and in neurotypical controls. Despite the strong a priori hypothesis of reduced GABA in autism spectrum disorder, we found no group differences in neurometabolite concentrations in any of the examined

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Section: Discussionmentioning

confidence: 54%

Section: Discussionmentioning

confidence: 99%

Concentrations of Cortical GABA and Glutamate in Young Adults With Autism Spectrum Disorder

et al. 2020

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“…Spectra were acquired using a short-echo semi-LASER sequence ( Öz and Tkáč, 2011 ; Deelchand et al , 2015 ) (repetition time/echo time = 5000/26 ms, 64 repetitions) using the recommended pre-scan protocol of FASTESTMAP shimming ( Gruetter and Tkáč, 2000 ) semi-LASER water-peak flip angle and VAPOR water suppression calibration ( Tkac et al , 1999 ). This spectroscopy sequence gives reliable and reproducible GABA and glutamate measurements in the human brain in vivo ( Barron et al , 2016 ; Kolasinski et al , 2017 ; Joers et al , 2018 ; Frangou et al , 2019 ; Hong et al , 2019 ; Ip et al , 2019 ).…”

Section: Methodsmentioning

confidence: 99%

GABA and glutamate deficits from frontotemporal lobar degeneration are associated with disinhibition

Murley

Rouse

Jones

et al. 2020

Brain

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Behavioural disinhibition is a common feature of the syndromes associated with frontotemporal lobar degeneration (FTLD). It is associated with high morbidity and lacks proven symptomatic treatments. A potential therapeutic strategy is to correct the neurotransmitter deficits associated with FTLD, thereby improving behaviour. Reductions in the neurotransmitters glutamate and GABA correlate with impulsive behaviour in several neuropsychiatric diseases and there is post-mortem evidence of their deficit in FTLD. Here, we tested the hypothesis that prefrontal glutamate and GABA levels are reduced by FTLD in vivo, and that their deficit is associated with impaired response inhibition. Thirty-three participants with a syndrome associated with FTLD (15 patients with behavioural variant frontotemporal dementia and 18 with progressive supranuclear palsy, including both Richardson’s syndrome and progressive supranuclear palsy-frontal subtypes) and 20 healthy control subjects were included. Participants undertook ultra-high field (7 T) magnetic resonance spectroscopy and a stop-signal task of response inhibition. We measured glutamate and GABA levels using semi-LASER magnetic resonance spectroscopy in the right inferior frontal gyrus, because of its strong association with response inhibition, and in the primary visual cortex, as a control region. The stop-signal reaction time was calculated using an ex-Gaussian Bayesian model. Participants with frontotemporal dementia and progressive supranuclear palsy had impaired response inhibition, with longer stop-signal reaction times compared with controls. GABA concentration was reduced in patients versus controls in the right inferior frontal gyrus, but not the occipital lobe. There was no group-wise difference in partial volume corrected glutamate concentration between patients and controls. Both GABA and glutamate concentrations in the inferior frontal gyrus correlated inversely with stop-signal reaction time, indicating greater impulsivity in proportion to the loss of each neurotransmitter. We conclude that the glutamatergic and GABAergic deficits in the frontal lobe are potential targets for symptomatic drug treatment of frontotemporal dementia and progressive supranuclear palsy.

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“…22,23 Optimized fMRS methodology, primarily using short echo-time (TE) 1 H-MRS protocols without J-editing, has consistently revealed activation-induced changes in various metabolites in the human brain. 4,5,24–27 Most consistently, BOLD activation of VC and MC is associated with increases of glutamate and lactate, and decreases of glucose and aspartate. Whereas BOLD activation of VC is also associated with a decrease in GABA, 25,28 BOLD deactivation of VC is associated with decreases of glutamate, lactate, and GABA.…”

Section: Introductionmentioning

confidence: 98%

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

Cited by 45 publications

References 56 publications

Concentrations of Cortical GABA and Glutamate in Young Adults With Autism Spectrum Disorder

Concentrations of Cortical GABA and Glutamate in Young Adults With Autism Spectrum Disorder

GABA and glutamate deficits from frontotemporal lobar degeneration are associated with disinhibition

Metabolic underpinnings of activated and deactivated cortical areas in human brain

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