Early excitatory and inhibitory modifications in the motor cortex following skill learning support motor memory consolidation and cortical plasticity overnight

Abstract

The learning of new motor skills constitutes an inseparable part of our lives. Motor consolidation refers to the offline processing of motor memories following the acquisition of new motor skills. The animal literature suggests that the primary motor cortex (M1) plays a key role in motor memory consolidation, and structural and functional plasticity in M1 following motor consolidation have been demonstrated. However, the mechanisms supporting motor memory consolidation and plasticity in the human M1 are not well understood. Initial human neuroimaging studies show that the initial stages of motor learning in humans are accompanied by short-term temporal dynamics of the brain main excitatory and inhibitory neurotransmitters, Glutamate (Glu) and GABA, in M1, but it remains unclear how these relate to the question of motor memory consolidation. Here, we show that early Glu and GABA modifications in M1 following motor skill learning may play vital roles in supporting motor memory consolidation and neural plasticity that take place over longer time scales. Using a multimodal magnetic resonance approach implemented on ultra-high field 7T scanner in healthy young adults (n=36), we found increased Glu and decreased GABA in M1 during the initial offline period following learning to support consolidation-related local and inter-regional functions of M1, such as motor memory reactivation and increased functional connectivity with the striatum. These neurochemical changes also correlated with overnight structural and functional plasticity expressed as increased M1 grey matter volume and functional connectivity, while Glu modifications also correlated with adaptive behavior, as reflected by improvements in skill performance. Our results provide intriguing microscale mechanistic evidence to the potential distinctive roles of Glu and GABA in promoting motor memory consolidation and plasticity in the human M1. They also highlight a role for early neurochemical modifications to memory consolidation and plasticity in the human brain and may hold important clinical implications in rehabilitative settings such as in stroke and brain injury.

Increased cortical inhibition immediately following brief motor memory reactivation supports reconsolidation and overnight offline learning gains

“…While those later findings are not directly related to reactivation or reconsolidation of existing motor memories, they further support the mechanistic link between the functionality of the GABAergic system and the potential to induce learning-related behavioral changes 24 . Lastly, our results are also in line with previous works demonstrating the importance of M1 processing during the early stages of initial motor memory consolidation, when the memory trace is still in an unstable state 15,21 .…”

“…Motor learning in humans has been previously characterized by GABAergic-mediated cortical disinhibition during learning 12,13 . Furthermore, recent findings in humans have demonstrated that the initial consolidation of motor memories may also depend on increased cortical excitation and GABAergic decrease that take place offline early following learning 15 , possibly reflecting the role of neuronal excitation in the facilitation of synaptic plasticity processes [16][17][18] .…”

“…Following its reactivation, a memory trace has been shown to become labile again and prone to modifications 6,8–11 , and reconsolidation is needed in order to restabilize it (i.e., making the memory once again resistant to interference) and promote skill improvements that develop after the practice session (i.e., offline learning gains). Neural inhibition and excitation (E-I) have been suggested to play a key role in the acquisition and consolidation of new motor skills in both animals and humans 12–15 ; we have therefore hypothesized they also play a fundamental role during the reconsolidation initiated by a brief reactivation. Changes in glutamate (Glu) and γ-aminobutyric acid (GABA), the main excitatory and inhibitory neurotransmitters in the brain, have been documented in the primary motor cortex (M1) both during 12,13 and following 14,15 the initial acquisition of motor skills.…”

“…Neural inhibition and excitation (E-I) have been suggested to play a key role in the acquisition and consolidation of new motor skills in both animals and humans 12–15 ; we have therefore hypothesized they also play a fundamental role during the reconsolidation initiated by a brief reactivation. Changes in glutamate (Glu) and γ-aminobutyric acid (GABA), the main excitatory and inhibitory neurotransmitters in the brain, have been documented in the primary motor cortex (M1) both during 12,13 and following 14,15 the initial acquisition of motor skills. Motor learning in humans has been previously characterized by GABAergic-mediated cortical disinhibition during learning 12,13 .…”

Increased cortical inhibition following brief motor memory reactivation supports reconsolidation and overnight offline learning gains

“…Following its reactivation, a memory trace has been shown to become labile again and prone to modifications ( 6 , 8 – 11 ), and reconsolidation is needed in order to restabilize it (i.e., making the memory once again resistant to interference) and promote skill improvements that develop after the practice session (i.e., offline learning gains). Neural excitation and inhibition (E-I) have been suggested to play a key role in the acquisition and consolidation of new motor skills in both animals and humans ( 12 – 15 ); we have therefore hypothesized they also play a fundamental role during the reconsolidation initiated by a brief reactivation. Changes in glutamate (Glu) and γ-aminobutyric acid (GABA), the main excitatory and inhibitory neurotransmitters in the brain, have been documented in the primary motor cortex (M1) both during ( 12 , 13 ) and following ( 14 , 15 ) the initial acquisition of motor skills.…”