Offline low-frequency rTMS of the primary and premotor cortices does not impact motor sequence memory consolidation despite modulation of corticospinal excitability

AbstractMotor skills are acquired and refined across alternating phases of practice (online) and subsequent consolidation in the absence of further skill execution (offline). Both stages of learning are sustained by dynamic interactions within a widespread motor learning network including the premotor and primary motor cortices. Here, we aimed to investigate the role of the dorsal premotor cortex (dPMC) and its interaction with the primary motor cortex (M1) during motor memory consolidation. Forty-eight healthy human participants (age 22.1 ± 3.1 years) were assigned to three different groups corresponding to either low-frequency (1 Hz) repetitive transcranial magnetic stimulation (rTMS) of left dPMC, rTMS of left M1, or sham rTMS. rTMS was applied immediately after explicit motor sequence training with the right hand. Motor evoked potentials were recorded before training and after rTMS to assess potential stimulation-induced changes in corticospinal excitability (CSE). Participants were retested on motor sequence performance after eight hours to assess consolidation. While rTMS of dPMC significantly increased CSE and rTMS of M1 significantly decreased CSE, no CSE modulation was induced by sham rTMS. However, all groups demonstrated similar significant offline learning indicating that consolidation was not modulated by the post-training low-frequency rTMS intervention despite evidence of an interaction of dPMC and M1 at the level of CSE. Motor memory consolidation ensuing explicit motor sequence training seems to be a rather robust process that is not affected by low-frequency rTMS-induced perturbations of dPMC or M1. Findings further indicate that consolidation of explicitly acquired motor skills is neither mediated nor reflected by post-training CSE.

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Contribution of the Premotor Cortex to Consolidation of Motor Sequence Learning in Humans During Sleep

Journal of Neurophysiology ◽

10.1152/jn.00611.2010 ◽

2010 ◽

Vol 104 (5) ◽

pp. 2603-2614 ◽

Cited By ~ 57

Author(s):

Michael A. Nitsche ◽

Michaela Jakoubkova ◽

Nivethida Thirugnanasambandam ◽

Leonie Schmalfuss ◽

Sandra Hullemann ◽

...

Keyword(s):

Reaction Time ◽

Task Performance ◽

Rem Sleep ◽

Sequence Learning ◽

Memory Consolidation ◽

Primary Motor Cortex ◽

Premotor Cortex ◽

Reaction Time Task ◽

Motor Memory ◽

Motor Sequence

Motor learning and memory consolidation require the contribution of different cortices. For motor sequence learning, the primary motor cortex is involved primarily in its acquisition. Premotor areas might be important for consolidation. In accordance, modulation of cortical excitability via transcranial DC stimulation (tDCS) during learning affects performance when applied to the primary motor cortex, but not premotor cortex. We aimed to explore whether premotor tDCS influences task performance during motor memory consolidation. The impact of excitability-enhancing, -diminishing, or placebo premotor tDCS during rapid eye movement (REM) sleep on recall in the serial reaction time task (SRTT) was explored in healthy humans. The motor task was learned in the evening. Recall was performed immediately after tDCS or the following morning. In two separate control experiments, excitability-enhancing premotor tDCS was performed 4 h after task learning during daytime or immediately before conduction of a simple reaction time task. Excitability-enhancing tDCS performed during REM sleep increased recall of the learned movement sequences, when tested immediately after stimulation. REM density was enhanced by excitability-increasing tDCS and reduced by inhibitory tDCS, but did not correlate with task performance. In the control experiments, tDCS did not improve performance. We conclude that the premotor cortex is involved in motor memory consolidation during REM sleep.

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Changes in TMS measures induced by repetitive TMS

10.1093/oxfordhb/9780198832256.013.19 ◽

2021 ◽

Author(s):

Joseph Classen ◽

Ying-Zu Huang ◽

Christoph Zrenner

Keyword(s):

Primary Motor Cortex ◽

Motor Evoked Potentials ◽

Repetitive Transcranial Magnetic Stimulation ◽

Low Frequency ◽

Corticospinal Excitability ◽

After Effects ◽

Before And After ◽

Neurophysiological Mechanisms ◽

Synaptic Changes ◽

Theta Burst

Commonly used repetitive transcranial magnetic stimulation (rTMS) protocols, including regular rTMS, intermittent and continuous theta-burst stimulation (TBS) and quadripulse stimulation (QPS) are presented with respect to their induced neuromodulatory after-effects and the underlying cellular and synaptic neurophysiological mechanisms. The anatomical target is typically primary motor cortex since motor evoked potentials (MEPs) before and after the intervention can be used to assess effects of the respective rTMS protocol. High-frequency regular rTMS and intermittent TBS protocols tend to increase corticospinal excitability as indexed by MEP amplitude, whereas low-frequency regular rTMS and continuous TBS protocols tend to reduce corticospinal excitability. These effects are primarily due to LTP-like and LTD-like synaptic changes mediated by GABA and NMDA receptors. Changes in the balance between excitatory and inhibitory cortical microcircuits play a secondary role, with inconsistent effects as determined by paired-pulse TMS protocols. Finally, the challenge of large inter-subject response variability, and current directions of research to optimize rTMS effects through EEG-dependent personalized TMS are discussed.

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Acquisition of motor memory determines the interindividual variability of learning-induced plasticity in the primary motor cortex

Journal of Applied Physiology ◽

10.1152/japplphysiol.00470.2018 ◽

2018 ◽

Vol 125 (4) ◽

pp. 990-998

Author(s):

Masato Hirano ◽

Shinji Kubota ◽

Yoshiki Koizume ◽

Kozo Funase

Keyword(s):

Motor Cortex ◽

Motor Skills ◽

Primary Motor Cortex ◽

Interindividual Variability ◽

Motor Evoked Potentials ◽

Plantar Flexion ◽

Skill Learning ◽

Tracking Task ◽

Motor Memory ◽

Visuomotor Tracking

Acquisition of new motor skills induces plastic reorganization in the primary motor cortex (M1). Previous studies have demonstrated the increases in the M1 excitability through motor skill learning. However, this M1 reorganization is highly variable between individuals even though they improve their skill performance through the same training protocol. To reveal the source of this interindividual variability, we examined the relationship between an acquisition of memory-guided feedforward movements and the learning-induced increases in the M1 excitability. Twenty-eight subjects participated in experiment 1. We asked subjects to learn a visuomotor tracking task. The subjects controlled a cursor on a PC monitor to pursue a target line by performing ankle dorsiflexion and plantar flexion. In experiment 1, we removed the online visual feedback provided by the cursor movement once every six trials, which enabled us to assess whether the subjects could perform accurate memory-guided movements. Motor-evoked potentials (MEP) were elicited in the tibialis anterior muscle by transcranial magnetic stimulation of the relevant M1 before and after the learning of the visuomotor tracking task and after half the trials. We found that the MEP amplitude was increased along with the improvement in memory-guided movements. In experiment 2 ( n = 10), we confirmed this relationship by examining whether the improvement in memory-guided movements induces increases in MEP amplitude. The results of this study indicate that the plastic reorganization of the M1 induced by the learning of a visuomotor skill is associated with the acquisition of memory-guided movements. NEW & NOTEWORTHY Acquisition of novel motor skills increases excitability of the primary motor cortex (M1). We recently reported that the amount of increases in the M1 excitability is highly variable between individuals even though they learned the same skill to the similar extent, yet the sources of this interindividual variability still remain unclear. The present study revealed that this interindividual variability is associated with whether individuals acquire a motor memory, which enables them to produce accurate memory-guided movements.

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Writing's Shadow: Corticospinal Activation during Letter Observation

Journal of Cognitive Neuroscience ◽

10.1162/jocn_a_00205 ◽

2012 ◽

Vol 24 (5) ◽

pp. 1138-1148 ◽

Cited By ~ 6

Author(s):

Masahiro Nakatsuka ◽

Mohamed Nasreldin Thabit ◽

Satoko Koganemaru ◽

Ippei Nojima ◽

Hidenao Fukuyama ◽

...

Keyword(s):

Primary Motor Cortex ◽

Motor Evoked Potentials ◽

Short Interval ◽

Single Pulse ◽

Random Order ◽

Intracortical Inhibition ◽

Corticospinal Excitability ◽

Motor Memory ◽

F Wave ◽

The Right

We can recognize handwritten letters despite the variability among writers. One possible strategy is exploiting the motor memory of orthography. By using TMS, we clarified the excitatory and inhibitory neural circuits of the motor corticospinal pathway that might be activated during the observation of handwritten letters. During experiments, participants looked at the handwritten or printed single letter that appeared in a random order. The excitability of the left and right primary motor cortex (M1) was evaluated by motor-evoked potentials elicited by single-pulse TMS. Short interval intracortical inhibition (SICI) of the left M1 was evaluated using paired-pulse TMS. F waves were measured for the right ulnar nerve. We found significant reduction of corticospinal excitability only for the right hand at 300–400 msec after each letter presentation without significant changes in SICI. This suppression is likely to be of supraspinal origin, because of no significant alteration in F-wave amplitudes. These findings suggest that the recognition of handwritten letters may include the implicit knowledge of “writing” in M1. The M1 activation associated with that process, which has been shown in previous neuroimaging studies, is likely to reflect the active suppression of the corticospinal excitability.

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Modulation of motor memory consolidation and corticospinal excitability following theta burst stimulation of the prefrontal cortex

10.26226/morressier.5b31ec532afeeb001345b820 ◽

2018 ◽

Author(s):

Mareike GANN

Keyword(s):

Prefrontal Cortex ◽

Memory Consolidation ◽

Corticospinal Excitability ◽

Motor Memory ◽

Theta Burst Stimulation ◽

Burst Stimulation ◽

Theta Burst ◽

Stimulation Of

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Cerebellar rTMS and PAS effectively induce cerebellar plasticity

Scientific Reports ◽

10.1038/s41598-021-82496-7 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Martje G. Pauly ◽

Annika Steinmeier ◽

Christina Bolte ◽

Feline Hamami ◽

Elinor Tzvi ◽

...

Keyword(s):

Motor Cortex ◽

Healthy Subjects ◽

Primary Motor Cortex ◽

Cortical Excitability ◽

Motor Evoked Potentials ◽

Repetitive Transcranial Magnetic Stimulation ◽

Premotor Cortex ◽

Motor Pathways ◽

Non Invasive ◽

Cerebellar Plasticity

AbstractNon-invasive brain stimulation techniques including repetitive transcranial magnetic stimulation (rTMS), continuous theta-burst stimulation (cTBS), paired associative stimulation (PAS), and transcranial direct current stimulation (tDCS) have been applied over the cerebellum to induce plasticity and gain insights into the interaction of the cerebellum with neo-cortical structures including the motor cortex. We compared the effects of 1 Hz rTMS, cTBS, PAS and tDCS given over the cerebellum on motor cortical excitability and interactions between the cerebellum and dorsal premotor cortex / primary motor cortex in two within subject designs in healthy controls. In experiment 1, rTMS, cTBS, PAS, and tDCS were applied over the cerebellum in 20 healthy subjects. In experiment 2, rTMS and PAS were compared to sham conditions in another group of 20 healthy subjects. In experiment 1, PAS reduced cortical excitability determined by motor evoked potentials (MEP) amplitudes, whereas rTMS increased motor thresholds and facilitated dorsal premotor-motor and cerebellum-motor cortex interactions. TDCS and cTBS had no significant effects. In experiment 2, MEP amplitudes increased after rTMS and motor thresholds following PAS. Analysis of all participants who received rTMS and PAS showed that MEP amplitudes were reduced after PAS and increased following rTMS. rTMS also caused facilitation of dorsal premotor-motor cortex and cerebellum-motor cortex interactions. In summary, cerebellar 1 Hz rTMS and PAS can effectively induce plasticity in cerebello-(premotor)-motor pathways provided larger samples are studied.

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0104 The Effect of Time, Sleep, and Wake on Motor Memory Consolidation: A Partial Replication of Walker, Et Al. (2002)

SLEEP ◽

10.1093/sleep/zsaa056.102 ◽

2020 ◽

Vol 43 (Supplement_1) ◽

pp. A41-A42

Author(s):

M Tucker ◽

I Wani

Keyword(s):

Memory Consolidation ◽

Memory Task ◽

Skill Learning ◽

Motor Memory ◽

Partial Replication ◽

Motor Sequence ◽

Training Performance ◽

Digit Sequence ◽

Larger Sample ◽

Typing Task

Abstract Introduction Findings from Walker, et al (2002) ‘Practice with Sleep Makes Perfect: Sleep-Dependent Motor Skill Learning’ demonstrate that performance on a widely used motor memory task (motor sequence task (MST)) benefits from a 12hr period of sleep (and not wake) even if the sleep period does not occur for approximately 12hrs after task acquisition, suggesting that sleep is crucial for motor memory consolidation. Using a larger sample, we attempted to replicate this finding, which is derived from Groups B & D from Walker et al (2002). Methods Participants (64 medical students: Age 21.2±0.8; N=33 females) were trained on the MST in the morning (10am; N=40) or evening (10pm; N=24) and then returned 12 and 24hrs later to be retested. The MST is a simple typing task that requires participants, at training, to type a 5-digit sequence (e.g., 4-1-3-2-4) as fast and accurately as possible over a series of 12 30-second trials with a 30-second break between each trial. At each retest, participants performed three 30-second trials. Results With 75% of the data collected we have found that when sleep follows training in the evening (first 12hr interval), the number of correctly typed sequences increased by 19.1% (cf. 20.5% in Walker (2002)). After a subsequent day of wake (second 12hr interval) performance increased by an additional 7.3% (cf. 2.0%). However, when a day of wake spanned the first 12hrs following training, performance increased by 14.5% (cf. 3.9%) followed by another 14.5% increase over the subsequent night (cf. 14.4%). Performance differences between sleep and wake participants were nonsignificant over the first 12hrs (p=0.38) and second 12hrs (p=0.49). Conclusion With most of data collection complete, our findings only partially replicate those of Walker et al (2002), and may draw into question the robustness of sleep for the processing motor memory. Support None

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EEG under TMS-induced SP reveals inhibitory effects of low-frequency rTMS on the primary motor cortex

Brain Stimulation ◽

10.1016/j.brs.2017.01.096 ◽

2017 ◽

Vol 10 (2) ◽

pp. 372 ◽

Cited By ~ 1

Author(s):

F. Jin ◽

J. Jin ◽

Y. Li ◽

X. Wang ◽

Z. Liu ◽

...

Keyword(s):

Motor Cortex ◽

Primary Motor Cortex ◽

Low Frequency ◽

Inhibitory Effects ◽

Low Frequency Rtms

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Changes in corticospinal excitability during reach adaptation in force fields

Journal of Neurophysiology ◽

10.1152/jn.00785.2012 ◽

2013 ◽

Vol 109 (1) ◽

pp. 124-136 ◽

Cited By ~ 24

Author(s):

Jean-Jacques Orban de Xivry ◽

Mohammad Ali Ahmadi-Pajouh ◽

Michelle D. Harran ◽

Yousef Salimpour ◽

Reza Shadmehr

Keyword(s):

Transcranial Magnetic Stimulation ◽

Magnetic Stimulation ◽

Primary Motor Cortex ◽

Motor Evoked Potentials ◽

Corticospinal Excitability ◽

Neural Basis ◽

Key Factor ◽

Gradual Group ◽

Specific Increase ◽

Stimulation Of

Both abrupt and gradually imposed perturbations produce adaptive changes in motor output, but the neural basis of adaptation may be distinct. Here, we measured the state of the primary motor cortex (M1) and the corticospinal network during adaptation by measuring motor-evoked potentials (MEPs) before reach onset using transcranial magnetic stimulation of M1. Subjects reached in a force field in a schedule in which the field was introduced either abruptly or gradually over many trials. In both groups, by end of the training, muscles that countered the perturbation in a given direction increased their activity during the reach (labeled as the on direction for each muscle). In the abrupt group, in the period before the reach toward the on direction, MEPs in these muscles also increased, suggesting a direction-specific increase in the excitability of the corticospinal network. However, in the gradual group, these MEP changes were missing. After training, there was a period of washout. The MEPs did not return to baseline. Rather, in the abrupt group, off direction MEPs increased to match on direction MEPs. Therefore, we observed changes in corticospinal excitability in the abrupt but not gradual condition. Abrupt training includes the repetition of motor commands, and repetition may be the key factor that produces this plasticity. Furthermore, washout did not return MEPs to baseline, suggesting that washout engaged a new network that masked but did not erase the effects of previous adaptation. Abrupt but not gradual training appears to induce changes in M1 and/or corticospinal networks.

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