The role of inhibition in human motor cortical plasticity

Bachtiar, Velicia; Stagg, Charlotte J.

doi:10.1016/j.neuroscience.2014.07.059

Cited by 57 publications

(48 citation statements)

References 111 publications

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“…Indeed, a series of animal studies support the notion that decreased inhibition improves learning (Collinson et al, 2002, 2006; Botta et al, 2015), while increased GABAergic neurotransmission impairs learning and memory formation (Davis, 1979; Sanger and Joly, 1985; McNaughton and Morris, 1987; Brioni et al, 1989; Arolfo and Brioni, 1991; Harris and Westbrook, 1995). Meanwhile, (opto-)genetic studies have started deciphering the functional connectivity of disinhibitory circuits and their relevance in associative synaptic plasticity and behavioral learning (reviewed in Letzkus et al, 2015), thus also confirming David Marr’s proposal (Marr, 1971) that local inhibitory networks set the threshold for producing long-term excitatory synaptic modifications (see also Douglas et al, 1982; Hsu et al, 1999; Ormond and Woodin, 2011; Bachtiar and Stagg, 2014). …”

Section: Role Of Disinhibitory Network In Behavioral Learningmentioning

confidence: 76%

Releasing the Cortical Brake by Non-Invasive Electromagnetic Stimulation? rTMS Induces LTD of GABAergic Neurotransmission

Lenz

Vlachos

2016

Front. Neural Circuits

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Repetitive Transcranial Magnetic Stimulation (rTMS) is a non-invasive brain stimulation technique which modulates cortical excitability beyond the stimulation period. However, despite its clinical use rTMS-based therapies which prevent or reduce disabilities in a functionally significant and sustained manner are scarce. It remains unclear how rTMS-mediated changes in cortical excitability, which are not task- or input-specific, exert beneficial effects in some healthy subjects and patients. While experimental evidence exists that repetitive magnetic stimulation (rMS) is linked to the induction of long-term potentiation (LTP) of excitatory neurotransmission, less attention has been dedicated to rTMS-induced structural, functional and molecular adaptations at inhibitory synapses. In this review article we provide a concise overview on basic neuroscience research, which reveals an important role of local disinhibitory networks in promoting associative learning and memory. These studies suggest that a reduction in inhibitory neurotransmission facilitates the expression of associative plasticity in cortical networks under physiological conditions. Hence, it is interesting to speculate that rTMS may act by decreasing GABAergic neurotransmission onto cortical principal neurons. Indeed, evidence has been provided that rTMS is capable of modulating inhibitory networks. Consistent with this suggestion recent basic science work discloses that a 10 Hz rTMS protocol reduces GABAergic synaptic strength on principal neurons. These findings support a model in which rTMS-induced long-term depression (LTD) of GABAergic synaptic strength mediates changes in excitation/inhibition-balance of cortical networks, which may in turn facilitate (or restore) the ability of stimulated networks to express input- and task-specific associative synaptic plasticity.

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Section: Role Of Disinhibitory Network In Behavioral Learningmentioning

confidence: 76%

Releasing the Cortical Brake by Non-Invasive Electromagnetic Stimulation? rTMS Induces LTD of GABAergic Neurotransmission

Lenz

Vlachos

2016

Front. Neural Circuits

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“…For example, we have shown that GABA in the occipital cortex correlates with performance on a visual orientation discrimination task (Edden et al, 2009) and that GABA measured in the sensorimotor cortex correlates with performance on a behavioral tactile frequency discrimination task (Puts et al, 2011). Other studies have shown correlations between in vivo GABA levels and individual differences in motor suppression (Boy et al, 2010), motor learning (Bachtiar and Stagg, 2014; Floyer-Lea et al, 2006), and the effect of peripheral modulation (Heba et al, 2016). Many of the studies also show that correlations between GABA and behavior are functionally and regionally specific.…”

Section: Introductionmentioning

confidence: 97%

Macromolecule-suppressed GABA measurements correlate more strongly with behavior than macromolecule-contaminated GABA+ measurements

et al. 2018

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The inhibitory neurotransmitter γ-aminobutyric acid (GABA) is known to be fundamental to the neuronal processes underlying visual orientation and vibrotactile frequency and amplitude discrimination. Previous studies have demonstrated that performance on visual and vibrotactile psychophysics tasks is associated with in vivo measurements of "GABA+" levels - a measure of GABA substantially contaminated by a macromolecular (MM) signal. Here, we establish that these prior findings are indeed driven by the GABA fraction of that signal. Edited magnetic resonance spectroscopy (MRS) was used to measure GABA with and without MM suppression in the sensorimotor (SM1) and occipital cortices in 14 healthy male adults. Volunteers also underwent psychophysical experiments to assess their performance on visual orientation discrimination and vibrotactile amplitude and frequency discrimination. We show that MM-suppressed GABA levels correlate more strongly with individual differences in vibrotactile (in the case of SM1 GABA; amplitude: r = -0.63, p = 0.03; frequency: r = -0.62, p = 0.02) and visual orientation (in the case of occipital GABA; r = -0.59, p = 0.05) discrimination thresholds than GABA levels contaminated by MM (vibrotactile amplitude: r = -0.36, p = 0.30; vibrotactile frequency: r = -0.53, p = 0.09; visual orientation: r = 0.21, p = 0.55). These findings further support the view that measurements of endogenous GABA acquired with edited MRS can usefully probe neurochemical-behavioral relationships in humans. Moreover, the more specific measurement of GABA used in this study provides increased statistical power to observe these regionally specific relationships.

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“…There is a strong body of evidence to suggest that a reduction in cortical inhibitory tone is critical for the induction of M1 plasticity (Bachtiar & Stagg, ; Peters et al . ).…”

Section: Introductionmentioning

confidence: 99%

The dynamics of cortical GABA in human motor learning

Kolasinski

Hinson

Zand

et al. 2018

The Journal of Physiology

150

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.

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The role of inhibition in human motor cortical plasticity

Cited by 57 publications

References 111 publications

Releasing the Cortical Brake by Non-Invasive Electromagnetic Stimulation? rTMS Induces LTD of GABAergic Neurotransmission

Releasing the Cortical Brake by Non-Invasive Electromagnetic Stimulation? rTMS Induces LTD of GABAergic Neurotransmission

Macromolecule-suppressed GABA measurements correlate more strongly with behavior than macromolecule-contaminated GABA+ measurements

The dynamics of cortical GABA in human motor learning

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The role of inhibition in human motor cortical plasticity

Cited by 57 publications

References 111 publications

Releasing the Cortical Brake by Non-Invasive Electromagnetic Stimulation? rTMS Induces LTD of GABAergic Neurotransmission

Releasing the Cortical Brake by Non-Invasive Electromagnetic Stimulation? rTMS Induces LTD of GABAergic Neurotransmission

Macromolecule-suppressed GABA measurements correlate more strongly with behavior than macromolecule-contaminated GABA+ measurements

The dynamics of cortical GABA in human motor learning

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Product

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Macromolecule-suppressed GABA measurements correlate more strongly with behavior than macromolecule-contaminated GABA+ measurements