Activation induced changes in GABA: Functional MRS at 7 T with MEGA-sLASER

Chen, Chen; Sigurdsson, Hilmar P.; Pépés, Sophia E.; Auer, Dorothee P.; Morris, Peter G.; Morgan, Paul S.; Gowland, Penny; Jackson, Stephen R.

doi:10.1016/j.neuroimage.2017.05.044

Cited by 50 publications

(79 citation statements)

References 66 publications

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“…This finding is consistent with the one previous study highligh ng reduced MRS-assessed GABA concentra ons in human M1 observed during a force-tracking learning task but not in an analogous Movement condi on (Floyer-Lea, 2006). However, these results are in contrast to a recent study repor ng evidence of a reduc on in MRS measures of GABA during a bi-manual whole-hand clench task (Chen et al, 2017). In light of differences in the rela ve balance of le and right M1 in the context of unimanual versus bimanual tasks (Koeneke et al, 2004), it is difficult to interpret the present results in the context of this study, where the concentra on of M1 GABA change may be impacted by a mixture top-down signals and M1-M1 interhemispheric signals that differs from those occurring in a unimanual task.…”

Section: Discussioncontrasting

confidence: 99%

The dynamics of cortical GABA in human motor learning

Kolasinski

Hinson

Zand

et al. 2018

Preprint

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The ability to learn novel motor skills is both a central part of our daily lives and can provide a model for rehabilitation after a stroke. However, there are still fundamental gaps in our understanding of the physiological mechanisms that underpin human motor plasticity. The acquisition of new motor skills is dependent on changes in local circuitry within the primary motor cortex (M1). This reorganisation has been hypothesised to be facilitated by a decrease in local inhibition via modulation of the neurotransmitter GABA, but this link has not been conclusively demonstrated in humans. Here, we used 7T MR Spectroscopy to investigate the dynamics of GABA concentrations in human M1 during the learning of an explicit, serial reaction time task. We observed a significant reduction in GABA concentration during motor learning that was not seen in an equivalent motor task lacking a learnable sequence, nor during a passive resting task of the same duration. No change in glutamate was observed in any group. Furthermore, baseline M1 GABA was strongly predictive of the degree of subsequent learning, such that greater inhibition was associated with poorer subsequent learning. This result suggests that higher levels of cortical inhibition may present a barrier that must be surmounted in order achieve an increase in M1 excitability, and hence encoding of a new motor skill. These results provide strong support for the mechanistic role of GABAergic inhibition in motor plasticity, raising questions regarding the link between population variability in motor learning and GABA metabolism in the brain.Funding informationJ.K.:Wellcome Trust Sir Henry Wellcome Postdoctoral Fellowship (204696/Z/16/Z). C.J.S.: Wellcome Trust/Royal Society Henry Dale Fellowships (102584/Z/13/Z).

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Section: Discussioncontrasting

confidence: 99%

The dynamics of cortical GABA in human motor learning

Kolasinski

Hinson

Zand

et al. 2018

Preprint

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“…Dynamic analysis of GABA and Glx revealed that the difference in GABA was largest early in the scan, whereas for Glx difference appeared to be relatively stable throughout. These results are broadly consistent with previous work (Bednařík et al, 2015;Chen et al, 2017;Lin, Stephenson, Xin, Napolitano, & Morris, 2012); however, whereas we found early differences in GABA, i.e., in the first 7 min of stimulation, (Chen et al, 2017) found the maximum difference after 5 min of hand-clenching. The distinct time courses found for GABA and Glx when viewing single-/mixed-polarity stereograms may reflect differences in the extent to which inhibitory/excitatory systems were engaged.…”

Section: Discussionsupporting

confidence: 93%

Mixed-polarity random-dot stereograms alter GABA and Glx concentration in the early visual cortex

Rideaux

Goncalves

Welchman

2019

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The offset between images projected onto the left and right retinae (binocular disparity) provides a powerful cue to the three-dimensional structure of the environment. It was previously shown that depth judgements are better when images comprise both light and dark features, rather than only dark or only light elements. Since Harris and Parker (1995) discovered the "mixed-polarity benefit", there has been limited evidence supporting their hypothesis that the benefit is due to separate bright and dark channels. Goncalves and Welchman (2017) observed that single-and mixed-polarity stereograms evoke different levels of positive and negative activity in a deep neural network trained on natural images to make depth judgements, which also showed the mixed-polarity benefit. Motivated by this discovery, here we seek to test the potential for changes in the balance of excitation and inhibition that are produced by viewing these stimuli. In particular, we use magnetic resonance spectroscopy to measure Glx and GABA concentration in the early visual cortex of adult humans while viewing single-and mixed-polarity random-dot stereograms (RDS). We find that observers' Glx concentration is significantly higher while GABA concentration is significantly lower when viewing mixed-polarity RDS than when viewing single-polarity RDS. These results indicate that excitation and inhibition facilitate processing of single-and mixedpolarity stereograms in the early visual cortex to different extents, consistent with recent theoretical work (Goncalves & Welchman, 2017).Binocular stereopsis is one of the primary cues for three-dimensional (3D) vision. It remains an important challenge to understand how the brain combines a pair of twodimensional retinal images to support 3D perception. A clue to understanding the neural computation of binocular stereopsis may be found in the observation that depth judgements are more accurate when binocular images are composed of both light and dark features, rather than just one or the other (Harris & Parker, 1995).This 'mixed-polarity benefit' was original explained on the basis that bright and dark features are processed by separate ON and OFF channels (Harris & Parker, 1995). Such neural infrastructure would reduce the number of potential binocular matches in a mixedpolarity stimulus, i.e., a random-dot stereogram (RDS), by as much as half, simplifying the stereoscopic correspondence problem considerably. Separate of ON and OFF channels first appear at the bipolar cell level as ON and OFF ganglia (Nelson, Famiglietti, & Kolb, 1978) and are maintained at the retinal ganglion and lateral geniculate nucleus level as ON and OFF centre cells. However, the convergence of ON and OFF channels in V1 to form simple cells (Schiller, 1992) seems to contradict this as a potential explanation for the mixed-polarity benefit.Recently, Goncalves and Welchman (2017) showed that it is possible to capture the mixed-polarity benefit using a simple linear -nonlinear processing architecture that did not depend on separate ON an...

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“…However, these results are in contrast to a recent study reporting evidence of a reduction in MRS measures of GABA during a bi‐manual whole‐hand clench task (Chen et al . ). In light of differences in the relative balance of left and right M1 in the context of unimanual versus bimanual tasks (Koeneke et al .…”

Section: Discussionmentioning

confidence: 97%

The dynamics of cortical GABA in human motor learning

Kolasinski

Hinson

Zand

et al. 2018

The Journal of Physiology

140

120

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Key points The ability to learn new motor skills is supported by plasticity in the structural and functional organisation of the primary motor cortex in the human brain.Changes inhibitory to signalling by GABA are thought to be crucial in inducing motor cortex plasticity.This study used magnetic resonance spectroscopy (MRS) to quantify the concentration of GABA in human motor cortex during a period of motor learning, as well as during a period of movement and a period at rest.We report evidence for a reduction in the MRS‐measured concentration of GABA specific to learning. Further, the GABA concentration early in the learning task was strongly correlated with the magnitude of subsequent learning: higher GABA concentrations were associated with poorer learning.The results provide initial insight into the neurochemical correlates of cortical plasticity associated with motor learning, specifically relevant in therapeutic efforts to induce cortical plasticity during recovery from stroke. AbstractThe ability to learn novel motor skills is a central part of our daily lives and can provide a model for rehabilitation after a stroke. However, there are still fundamental gaps in our understanding of the physiological mechanisms that underpin human motor plasticity. The acquisition of new motor skills is dependent on changes in local circuitry within the primary motor cortex (M1). This reorganisation has been hypothesised to be facilitated by a decrease in local inhibition via modulation of the neurotransmitter GABA, but this link has not been conclusively demonstrated in humans. Here, we used 7 T magnetic resonance spectroscopy to investigate the dynamics of GABA concentrations in human M1 during the learning of an explicit, serial reaction time task. We observed a significant reduction in GABA concentration during motor learning that was not seen in an equivalent motor task lacking a learnable sequence, nor during a passive resting task of the same duration. No change in glutamate was observed in any group. Furthermore, M1 GABA measured early in task performance was strongly correlated with the degree of subsequent learning, such that greater inhibition was associated with poorer subsequent learning. This result suggests that higher levels of cortical inhibition may present a barrier that must be surmounted in order to achieve an increase in M1 excitability, and hence encoding of a new motor skill. These results provide strong support for the mechanistic role of GABAergic inhibition in motor plasticity, raising questions regarding the link between population variability in motor learning and GABA metabolism in the brain.

show abstract

Activation induced changes in GABA: Functional MRS at 7 T with MEGA-sLASER

Cited by 50 publications

References 66 publications

The dynamics of cortical GABA in human motor learning

The dynamics of cortical GABA in human motor learning

Mixed-polarity random-dot stereograms alter GABA and Glx concentration in the early visual cortex

The dynamics of cortical GABA in human motor learning

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