The dynamics of cortical GABA in human motor learning

Abstract

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.

Hippocampal and striatal responses during motor learning are modulated by prefrontal cortex stimulation

“…These results suggest that, under the effect of excitatory stimulation, motor sequence learning, in comparison to random motor execution, resulted in a decrease in DLPFC inhibitory tone. Interestingly, these results are in line with evidence of learning-induced decreases in M1 GABA levels during (Kolasinski et al, 2018), immediately after (Floyer-Lea et al, 2006) but also after 6 weeks of motor sequence learning (Sampaio-Baptista et al, 2015). Importantly and consistent with our results, these M1 GABA changes have been described to be learning-specific, as no such effects were observed after random task practice (Floyer-Lea et al, 2006;Kolasinski et al, 2018).…”

“…Importantly and consistent with our results, these M1 GABA changes have been described to be learning-specific, as no such effects were observed after random task practice (Floyer-Lea et al, 2006;Kolasinski et al, 2018). We argue that, similar to M1, the decrease in DLPFC GABA+ levels might reflect disinhibition processes that promote successful learning (Kolasinski et al, 2018;Stagg et al, 2011).…”

“…Interestingly, these results are in line with evidence of learning-induced decreases in M1 GABA levels during (Kolasinski et al, 2018), immediately after (Floyer-Lea et al, 2006) but also after 6 weeks of motor sequence learning (Sampaio-Baptista et al, 2015). Importantly and consistent with our results, these M1 GABA changes have been described to be learning-specific, as no such effects were observed after random task practice (Floyer-Lea et al, 2006;Kolasinski et al, 2018). We argue that, similar to M1, the decrease in DLPFC GABA+ levels might reflect disinhibition processes that promote successful learning (Kolasinski et al, 2018;Stagg et al, 2011).…”

“…Based on models suggesting that hippocampo-prefrontal networks exert control processes over sensorimotor-striato-cortical networks during MSL (Albouy, King, et al, 2013), we expected that facilitatory iTBS and inhibitory cTBS of the DLPFC would repress and facilitate, respectively, the development of striato-motor activity during sequence learning as compared to random practice. With respect to the effects on GABA, previous MRS studies have shown that M1 GABA levels can be altered by both M1 brain stimulation (Bachtiar et al, 2018;Bachtiar, Near, Johansen-Berg, & Stagg, 2015;Marjańska et al, 2013;Stagg, Bachtiar, & Johansen-Berg, 2011;Stagg, Best, et al, 2009; and motor learning (Floyer-Lea, Wylezinska, Kincses, & Matthews, 2006;Kolasinski et al, 2018;Sampaio-Baptista et al, 2015).…”

Motor learning enhanced by combined motor imagery and noninvasive brain stimulation is associated with reduced short‐interval intracortical inhibition

“…Pharmacological studies have suggested that SICI is mediated by type A gamma‐aminobutyric acid (GABA A ) receptors (Di Lazzaro et al, ). Studies of the human motor cortex using TMS have reported increased cortical excitability and decreased SICI after motor learning (Leung, Rantalainen, Teo, & Kidgell, ; Rosenkranz, Kacar, & Rothwell, ), suggesting that GABA A plays an important role in human motor learning (Kolasinski & Hinson, ).…”