Glutamatergic metabolites are associated with visual plasticity in humans

Wijtenburg, S. Andrea; West, Jeffrey; Korenic, Stephanie A.; Kuhney, Franchesca S.; Gaston, Frank; Chen, Hongji; Roberts, Meredith; Kochunov, Peter; Hong, L. Elliot; Rowland, Laura M.

doi:10.1016/j.neulet.2017.02.020

Cited by 21 publications

(35 citation statements)

References 72 publications

(86 reference statements)

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“…There is growing evidence that the neurotransmitters gamma-aminobutyric acid (GABA) and glutamate (Glu) are functionally related to standard learning paradigms. For example, GABAergic disinhibition appears to be crucial to learning in the motor cortex ( Floyer-Lea et al, 2006 ; Kolasinski et al, 2019 ; Stagg et al, 2011 ), and there appears to be a positive relationship between resting state Glu, glutamine (Gln), or GABA levels and plasticity in the visual and sensory cortices ( Edden et al, 2009 ; Heba et al, 2016 ; Wijtenburg et al., 2017 ). In the case of perceptual learning, it has been shown that plasticity changes induced by presentation of repetitive stimulation applied to the finger tips is abolished in the presence of lorazepam, a GABA A receptor agonist ( Dinse et al., 2003a ).…”

Section: Introductionsupporting

confidence: 89%

GABA Modulates Frequency-Dependent Plasticity in Humans

et al. 2020

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Summary Frequency-dependent reorganization of the primary somatosensory cortex, together with perceptual changes, arises following repetitive sensory stimulation. Here, we investigate the role of GABA in this process. We co-stimulated two finger tips and measured GABA and Glx using magnetic resonance (MR) spectroscopy at the beginning and end of the stimulation. Participants performed a perceptual learning task before and after stimulation. There were 2 sessions with stimulation frequency either at or above the resonance frequency of the primary somatosensory cortex (23 and 39 Hz, respectively). Perceptual learning occurred following above resonance stimulation only, while GABA reduced during this condition. Lower levels of early GABA were associated with greater perceptual learning. One possible mechanism underlying this finding is that cortical disinhibition “unmasks” lateral connections within the cortex to permit adaptation to the sensory environment. These results provide evidence in humans for a frequency-dependent inhibitory mechanism underlying learning and suggest a mechanism-based approach for optimizing neurostimulation frequency.

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Section: Introductionsupporting

confidence: 89%

GABA Modulates Frequency-Dependent Plasticity in Humans

et al. 2020

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“…Neural activity in the occipital lobe was also studied in different contexts beyond simple visual perception. Wijtenburg ( 17 ) found a positive correlation between GABA and neural activation difference before and after a high frequency visual stimulus, an effect thought to reflect visual plasticity. In agreement with other studies, when only baseline visual stimulation-related activation was used, a negative correlation was found with GABA levels.…”

Section: Resultsmentioning

confidence: 99%

GABA, Glutamate and Neural Activity: A Systematic Review With Meta-Analysis of Multimodal 1H-MRS-fMRI Studies

et al. 2021

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Multimodal neuroimaging studies combining proton magnetic resonance spectroscopy (1H-MRS) to quantify GABA and/or glutamate concentrations and functional magnetic resonance imaging (fMRI) to measure brain activity non-invasively have advanced understanding of how neurochemistry and neurophysiology may be related at a macroscopic level. The present study aimed to perform a systematic review and meta-analysis of available studies examining the relationship between 1H-MRS glutamate and/or GABA levels and task-related fMRI signal in the healthy brain. Ovid (Medline, Embase, and PsycINFO) and Pubmed databases were systematically searched to identify articles published until December 2019. The primary outcome of interest was the association between resting levels of glutamate or GABA and task-related fMRI. Fifty-five papers were identified for inclusion in the systematic review. A further 22 studies were entered into four separate meta-analyses. These meta-analyses found evidence of significant negative associations between local GABA levels and (a) fMRI activation to visual tasks in the occipital lobe, and (b) activation to emotion processing in the medial prefrontal cortex (mPFC)/anterior cingulate cortex (ACC). However, there was no significant association between mPFC/ACC glutamate levels and fMRI activation to cognitive control tasks or to emotional processing, with the relationship to emotion processing related neural activity narrowly missing significance. Moreover, our systematic review also found converging evidence of negative associations between GABA levels and local brain activity, and positive associations between glutamate levels and distal brain activity, outside of the 1H-MRS sampling region. Albeit less consistently, additional relationships between GABA levels and distal brain activity and between glutamate levels and local brain activity were found. It remains unclear if the absence of effects for other brain regions and other cognitive-emotional domains reflects study heterogeneity or potential confounding effects of age, sex, or other unknown factors. Advances in 1H-MRS methodology as well as in the integration of 1H-MRS readouts with other imaging modalities for indexing neural activity hold great potential to reveal key aspects of the pathophysiology of mental health disorders involving aberrant interactions between neurochemistry and neurophysiology such as schizophrenia.

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“…Voxels were placed in the midsagittal slice in the occipital cortex ( Figure 1). Data presented here are part of a study of visual plasticity (data not presented but HC published elsewhere (Wijtenburg et al, 2017)) and memory function, thus the rationale for assessing the occipital cortex. Participants were asked to keep their eyes open and remain awake during the study.…”

Section: Magnetic Resonance Spectroscopymentioning

confidence: 99%

Brain insulin resistance and altered brain glucose are related to memory impairments in schizophrenia

Wijtenburg

Kapogiannis

Korenic

et al. 2019

Schizophrenia Research

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Memory is robustly impaired in schizophrenia (SZ) and related to functional outcome. Memory dysfunction has been shown to be related to altered brain glucose metabolism and brain insulin resistance in animal models and human studies of Alzheimer's disease. In this study, differences in brain glucose using magnetic resonance spectroscopy (MRS) and blood Extracellular Vesicle (EV) biomarkers of neuronal insulin resistance (i.e. Akt and signaling effectors) between SZ and controls were investigated, as well as whether these measures were related to memory impairments. Neuronal insulin resistance biomarkers showed a trend for being lower in SZ compared to controls, and memory measures were lower in SZ compared to controls. Occipital cortex glucose was higher in SZ compared to controls indicating lower brain glucose utilization. Linear regression analyses revealed significant relationships between neuronal insulin resistance biomarkers, memory measures, and brain glucose. More specifically, p70S6K, an insulin signaling effector, was related to verbal learning and brain MRS glucose in the SZ group. For the first time, we show that memory impairments in SZ may be related to brain glucose and brain insulin resistance. These data suggest that brain insulin resistance may play a role in the pathophysiology of learning and memory dysfunction in SZ.

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Glutamatergic metabolites are associated with visual plasticity in humans

Cited by 21 publications

References 72 publications

GABA Modulates Frequency-Dependent Plasticity in Humans

GABA Modulates Frequency-Dependent Plasticity in Humans

GABA, Glutamate and Neural Activity: A Systematic Review With Meta-Analysis of Multimodal 1H-MRS-fMRI Studies

Brain insulin resistance and altered brain glucose are related to memory impairments in schizophrenia

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