Modulation of dorsal premotor cortex differentially influences I‐wave excitability in primary motor cortex of young and older adults

First published: 16 May 2023Previous research using transcranial magnetic stimulation (TMS) has demonstrated weakened connectivity between dorsal premotor cortex (PMd) and motor cortex (M1) with age. While this alteration is probably mediated by changes in the communication between the two regions, the effect of age on the influence of PMd on specific indirect (I) wave circuits within M1 remains unclear. The present study therefore investigated the influence of PMd on early and late I-wave excitability inM1of young and older adults. Twenty-two young (mean±SD, 22.9±2.9 years) and 20 older (66.6 ± 4.2 years) adults participated in two experimental sessions involving either intermittent theta burst stimulation (iTBS) or sham stimulation over PMd. Changes within M1 following the intervention were assessed with motor-evoked potentials (MEPs) recorded from the right first dorsal interosseous muscle. We applied posterior–anterior (PA) and anterior–posterior (AP) current single-pulse TMS to assess corticospinal excitability (PA1mV; AP1mV; PA0.5mV, early; AP0.5mV, late), and paired-pulse TMS short intracortical facilitation for I-wave excitability (PA SICF, early; AP SICF, late). Although PMd iTBS potentiated PA1mV and AP1mV MEPs in both age groups (both P < 0.05), the time course of this effect was delayed for AP1mV in older adults (P = 0.001). Furthermore, while AP0.5mV, PA SICF and AP SICF were potentiated in both groups (all P < 0.05), potentiation of PA0.5mV was only apparent in young adults (P < 0.0001).While PMd influences early and late I-wave excitability in young adults, direct PMdmodulation of the early circuits is specifically reduced in older adults.Wei-Yeh Liao, George M. Opie, Ulf Ziemann, and John G. Semmle

Boosting brain plasticity in older adults with non-invasive brain co-stimulation

Abstract not availableJohn G.Semmler, George M.Opi

Preferential activation of unique motor cortical networks with transcranial magnetic stimulation: a review of the physiological, functional, and clinical evidence

Objectives: The corticospinal volley produced by application of transcranial magnetic stimulation (TMS) over primary motor cortex consists of a number of waves generated by trans-synaptic input from interneuronal circuits. These indirect (I)-waves mediate the sensitivity of TMS to cortical plasticity and intracortical excitability and can be assessed by altering the direction of cortical current induced by TMS. While this methodological approach has been conventionally viewed as preferentially recruiting early or late I-wave inputs from a given populations of neurons, growing evidence suggests recruitment of different neuronal populations, and this would strongly influence interpretation and application of these measures. The aim of this review is therefore to consider the physiological, functional, and clinical evidence for the independence of the neuronal circuits activated by different current directions. Materials and Methods: To provide the relevant context, we begin with an overview of TMS methodology, focusing on the different techniques used to quantify I-waves. We then comprehensively review the literature that has used variations in coil orientation to investigate the I-wave circuits, grouping studies based on the neurophysiological, functional, and clinical relevance of their outcomes. Results: Review of the existing literature reveals significant evidence supporting the idea that varying current direction can recruit different neuronal populations having unique functionally and clinically relevant characteristics. Conclusions: Further research providing greater characterization of the I-wave circuits activated with different current directions is required. This will facilitate the development of interventions that are able to modulate specific intracortical circuits, which will be an important application of TMS.George M. Opie, John G. Semmle

Threshold Tracked Short-Interval Intracortical Inhibition More Closely Predicts the Cortical Response to Transcranial Magnetic Stimulation

Vol. 25(4) pp 614-623Objectives: Short-interval intracortical inhibition (SICI) is a paired-pulse transcranial magnetic stimulation (TMS) technique that is commonly used to quantify intracortical inhibitory tone in the primary motor cortex. Whereas conventional measures of SICI (CSICI) quantify inhibition by the amplitude of the motor evoked potential (MEP), alternative measures involving threshold tracked SICI (TT-SICI) instead record the TMS intensity required to maintain a consistent MEP amplitude. Although both C-SICI and TT-SICI are thought to reflect inhibition mediated by γ-aminobutyric acid type A (GABAA) receptors, recent evidence suggests that the mechanisms involved with each measure may not be equivalent. This study aimed to use combined TMSelectroencephalography (TMS-EEG) to investigate the cortical mechanisms contributing to C-SICI and TT-SICI. Materials and Methods: In 20 young adults (30.6 ± 8.1 years), C-SICI and TT-SICI were recorded with multiple conditioning intensities, using both posterior-to-anterior (PA) and anterior-to-posterior (AP) induced currents, and this was compared with the TMS-evoked EEG potential (TEP). Results: We found no relationship between the magnitude of C-SICI and TT-SICI within each current direction. However, there was a positive relationship between the slope (derived from multiple conditioning intensities) of inhibition recorded with C-SICI and TT-SICI, but only with a PA current. Furthermore, irrespective of conditioning intensity or current direction, measures of C-SICI were unrelated to TEP amplitude. In contrast, TT-SICI was predicted by the P30 generated with AP stimulation. Conclusions: Our findings further demonstrate that C-SICI and TT-SICI likely reflect different facets of GABAA-mediated processes, with inhibition produced by TT-SICI appearing to align more closely with TMS-EEG measures of cortical excitability.Ryoki Sasaki, John G. Semmler, George M. Opi

Interactions between cerebellum and the intracortical excitatory circuits of motor cortex: a mini-review

Published: 12 May 2021 OnlinePublInteractions between cerebellum (CB) and primary motor cortex (M1) are critical for effective motor function. Although the associated neurophysiological processes are yet to be fully characterised, a growing body of work using non-invasive brain stimulation (NIBS) techniques has significantly progressed our current understanding. In particular, recent developments with both transcranial magnetic (TMS) and direct current (tDCS) stimulation suggest that CB modulates the activity of local excitatory interneuronal circuits within M1. These circuits are known to be important both physiologically and functionally, and understanding the nature of their connectivity with CB therefore has the potential to provide important insight for NIBS applications. Consequently, this mini-review provides an overview of the emerging literature that has investigated interactions between CB and the intracortical excitatory circuits of M1.George M. Opie, Wei-Yeh Liao and John G. Semmle

Motor cortex plasticity and visuomotor skill learning in upper and lower limbs of endurance-trained cyclists

Published online: 7 October 2021Purpose: Studies with transcranial magnetic stimulation (TMS) show that both acute and long-term exercise can influence TMS-induced plasticity within primary motor cortex (M1). However, it remains unclear how regular exercise influences skill training-induced M1 plasticity and motor skill acquisition. This study aimed to investigate whether skill training-induced plasticity and motor skill learning is modified in endurance-trained cyclists. Methods: In 16 endurance-trained cyclists (24.4 yrs; 4 female) and 17 sedentary individuals (23.9 yrs; 4 female), TMS was applied in 2 separate sessions: one targeting a hand muscle not directly involved in habitual exercise and one targeting a leg muscle that was regularly trained. Single- and paired-pulse TMS was used to assess M1 and intracortical excitability in both groups before and after learning a sequential visuomotor isometric task performed with the upper (pinch task) and lower (ankle dorsiflexion) limb. Results: Endurance-trained cyclists displayed greater movement times (slower movement) compared with the sedentary group for both upper and lower limbs (all P  0.05). Furthermore, endurance-trained cyclists demonstrated a greater increase in M1 excitability and reduced modulation of intracortical facilitation in resting muscles of upper and lower limbs after visuomotor skill learning (all P < 0.005). Conclusion: Under the present experimental conditions, these results indicate that a history of regular cycling exercise heightens skill training-induced M1 plasticity in upper and lower limb muscles, but it does not facilitate visuomotor skill acquisition.Brodie J. Hand, George M. Opie, Simranjit K. Sidhu, John G. Semmle

Motor cortex plasticity is greater in endurance-trained cyclists following acute exercise

First published September 8, 2022Previous research using transcranial magnetic stimulation (TMS) has shown that plasticity within primary motor cortex (M1) is greater in people who undertake regular exercise, and a single session of aerobic exercise can increase M1 plasticity in untrained participants. This study aimed to examine the effect of an acute bout of exercise on M1 plasticity in endurance-trained (cyclists) and sedentary individuals. 14 endurance-trained cyclists (mean ± SD; 23 ± 3.8 years) and 14 sedentary individuals (22 ± 1.8 years) performed two experimental sessions. One session included an acute bout of high-intensity interval training (HIIT) exercise involving stationary cycling, while another session involved no-exercise (control). Following exercise (or control), I-wave periodicity repetitive TMS (iTMS) was used (1.5 ms interval, 180 pairs) to induce plasticity within M1. Motor evoked potentials (MEP) induced by single and paired-pulse TMS over M1 were recorded from a hand muscle at baseline, after HIIT (or control) exercise, and after iTMS. Corticospinal and intracortical excitability was not influenced by HIIT exercise in either group (all P &gt; 0.05). There was an increase in MEP amplitude after iTMS, and this was greater after HIIT exercise (compared with control) for all subjects (P &lt; 0.001). However, the magnitude of this response was larger in endurance cyclists compared with the sedentary group (P &lt; 0.05). These findings indicate that M1 plasticity induced by iTMS was greater in endurance-trained cyclists following HIIT. Prior history of exercise training is, therefore, an important consideration for understanding factors that contribute to exercise-induced plasticity.Brodie J. Hand, George M. Opie, Simranjit K. Sidhu and John G. Semmle

Investigating the influence of paired-associative stimulation on multi-session skill acquisition and retention in older adults

Abstract not available.George M. Opie, Maryam Pourmajidian, Ulf Ziemann, John G. Semmle

TMS coil orientation and muscle activation influence lower limb intracortical excitability

Introduction: Previous research with transcranial magnetic stimulation (TMS) indicates that coil orientation (TMS current direction) and muscle activation state (rest or active) modify corticospinal and intracortical excitability of upper limb muscles. However, the extent to which these factors influence corticospinal and intracortical excitability of lower limb muscles is unknown. This study aimed to examine how variations in coil orientation and muscle activation affect corticospinal and intracortical excitability of tibialis anterior (TA), a lower leg muscle. Methods: In 21 young (21.6 ± 3.3 years, 11 female) adults, TMS was administered to the motor cortical representation of TA in posterior-anterior (PA) and mediolateral (ML) orientations at rest and during muscle activation. Single-pulse TMS measures of motor evoked potential amplitude, in addition to resting and active motor thresholds, were used to index corticospinal excitability, whereas paired-pulse TMS measures of short-interval intracortical inhibition (SICI) and facilitation (SICF), and long-interval intracortical inhibition (LICI), were used to assess excitability of intracortical circuits. Results: For single-pulse TMS, motor thresholds and test TMS intensity were lower for ML stimulation (all P < 0.05). In a resting muscle, ML TMS produced greater SICI (P < 0.001) and less SICF (both P < 0.05) when compared with PA TMS. In contrast, ML TMS in an active muscle resulted in reduced SICI but increased SICF (both P ≤ 0.001) when compared with PA TMS. CONCLUSION: TMS coil orientation and muscle activation influence measurements of intracortical excitability recorded in the tibialis anterior, and are therefore important considerations in TMS studies of lower limb muscles.Brodie J. Hand, George M. Opie, Simranjit K. Sidhu, John G. Semmle

Modulation of I-Wave Generating Pathways With Repetitive Paired-Pulse Transcranial Magnetic Stimulation: A Transcranial Magnetic Stimulation - Electroencephalography Study

OnlinePublObjectives: Repetitive paired-pulse transcranial magnetic stimulation (iTMS) at indirect (I) wave intervals increases motorevoked potentials (MEPs) produced by transcranial magnetic stimulation (TMS) to primary motor cortex (M1). However, the effects of iTMS at early and late intervals on the plasticity of specific I-wave circuits remain unclear. This study therefore aimed to assess how the timing of iTMS influences intracortical excitability within early and late I-wave circuits. To investigate the cortical effects of iTMS more directly, changes due to the intervention were also assessed using combined TMSelectroencephalography (EEG). Material and Methods: Eighteen young adults (aged 24.6 ± 4.2 years) participated in four sessions in which iTMS targeting early (1.5-millisecond interval; iTMS1.5) or late (4.0-millisecond interval; iTMS4.0) I-waves was applied over M1. Neuroplasticity was assessed using both posterior-to-anterior (PA) and anterior-to-posterior (AP) stimulus directions to record MEPs and TMS-evoked EEG potentials (TEPs) before and after iTMS. Short-interval intracortical facilitation (SICF) at interstimulus intervals of 1.5 and 4.0 milliseconds was also used to index I-wave activity. Results: MEP amplitude was increased after iTMS (p < 0.01), and this was greater for PA responses (p < 0.01) but not different between iTMS intervals (p = 0.9). Irrespective of iTMS interval and coil current, SICF was facilitated after the intervention (p < 0.01). Although the N45 produced by AP stimulation was decreased by iTMS1.5 (p = 0.04), no other changes in TEP amplitude were observed. Conclusions: The timing of iTMS failed to influence which I-wave circuits were potentiated by the intervention. In contrast, decreases in the N45 suggest that the neuroplastic effects of iTMS may include disinhibition of intracortical inhibitory processes.Ryoki Sasaki, Brodie J. Hand, John G. Semmler, George M. Opi