Corticospinal and intracortical excitability is modulated in the knee extensors after acute strength training

This is a self-archived version of an original article. This version may differ from the original in pagination and typographic details. Author(s): Title: Year: Version: Copyright: Rights: Rights url: Please cite the original version: CC BY-NC-ND 4.0 https://creativecommons.org/licenses/by-nc-nd/4.0/ Corticospinal and intracortical excitability is modulated in the knee extensors after acute strength training © 2021 Informa UK Limited, trading as Taylor & Francis Group Accepted version (Final draft) Alibazi, Razie J.; Frazer, Ashlyn K.; Pearce, Alan J.; Tallent, Jamie; Avela, Janne; Kidgell, Dawson J. Alibazi, R. J., Frazer, A. K., Pearce, A. J., Tallent, J., Avela, J., & Kidgell, D. J. (2022). Corticospinal and intracortical excitability is modulated in the knee extensors after acute strength training. Journal of Sports Sciences, 40(5), 561-570. https://doi.org/10.1080/02640414.2021.2004681 2022 1 Corticospinal and intracortical excitability is modulated in the knee extensors after acute strength 1 training. 2 3 Razie J Alibazi M.Sc1, Ashlyn K Frazer PhD1, Alan J Pearce PhD2, Jamie Tallent PhD1,3, Janne Avela PhD4, 4 Dawson J Kidgell PhD1. 5 6 1Department of Physiotherapy, School of Primary and Allied Health Care, Faculty of Medicine, Nursing and 7 Health Science, Monash University, Melbourne, Australia. 8 9 2College of Science, Health and Engineering, La Trobe University, Melbourne, Australia 10 11 3 School of Sport, Rehabilitation and Exercise Sciences, University of Essex, Wivenhoe Park, Colchester, 12 England. 13 14 4NeuroMuscular Research Center, Faculty of Sport and Health Sciences, University of Jyväskylä, Finland 15 16 17 18 19 20 21 Address for Corresponding author: 22 Dawson J Kidgell, PhD. 23 Department of Physiotherapy, School of Primary and Allied Health Care, Faculty of Medicine, Nursing and Health 24 Science, Monash University, PO Box 527 Frankston, Victoria, Australia, 3199. 25 Email: [email protected] 26 27 28 29 30 31 32 33 34 2 ABSTRACT 35 The corticospinal-responses to high-intensity and low-intensity strength-training of the upper-limb are modulated 36 in an intensity-dependent manner. Whether an intensity-dependent threshold occurs following acute strength37 training of the knee extensors (KE) remains unclear. We assessed the corticospinal-responses to an acute bout 38 of either high-intensity (85% of maximal strength) or low-intensity (30% of maximal strength) KE strength-training 39 with measures taken during an isometric KE task at baseline, post 5, 30 and 60 minutes. Twenty-eight healthy 40 volunteers (23 ± 3 years) were randomized to high-intensity (n = 11), low-intensity (n = 10) or to a control group (n 41 = 7). Corticospinal-responses were evoked with transcranial magnetic stimulation (TMS) at intracortical and 42 corticospinal levels. An acute bout of highor lowintensity KE strength-training had no effect on maximum 43 voluntary contraction (MVC) force post-exercise (P > 0.05). High-intensity training increased corticospinal 44 excitability (range 130% to 180%) from 5-60 minutes post-exercise compared to low-intensity training (17-30% 45 increase). Large effect sizes (ES) showed that short-interval cortical inhibition (SICI) was reduced only for the high46 intensity training group from 5-60 minutes post-exercise (24-44% decrease), compared to low-intensity (ES ranges 47 1-1.3). These findings show a training-intensity threshold is required to adjust CSE and SICI following strength 48 training in the lower-limb. 49 50 Key words: corticospinal excitability, exercise, intracortical inhibition, knee extension, maximal strength. 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 66 67 68 69 70 71 3 INTRODUCTION 72 It is axiomatic that short-term strength training (i.e., 4-8 weeks) is associated with increases in muscle strength 73 (Tallent, Woodhead et al. 2021). However, during the early phases of strength development, gains in strength 74 cannot be explained completely by muscular factors alone (Siddique, Rahman et al. 2020). Rather, much of the 75 initial increase in strength is due to subtle changes along the neuroaxis which include a change in plasticity at 76 supraspinal (Latella, Kidgell et al. 2012, Weier, Pearce et al. 2012) and spinal levels (Aagaard, Simonsen et al. 77 2002). Common short-term neural adaptations to strength training include increased muscle activation as assessed 78 by increased integrated electromyography (EMG) (Moritani and deVries 1979, Narici, Roi et al. 1989), increased 79 recruitment and/or discharge rates of spinal motoneurons (Del Vecchio, Casolo et al. 2019), reduced co-contraction 80 of antagonists (Mason, Howatson et al. 2019), changes in corticospinal excitability (CSE) and inhibition as 81 assessed by transcranial magnetic stimulation (TMS) (Siddique, Rahman et al. 2020). 82 83 From only a single set of strength training (Ruotsalainen, Ahtiainen et al. 2014) and following a single session of 84 strength training, recent studies using TMS have reported a modulation in neuroplasticity of the corticospinal tract 85 (CST) (Latella, Teo et al. 2017, Mason, Frazer et al. 2019, Mason, Frazer et al. 2019, Mason, Howatson et al. 86 2019, Ansdell, Brownstein et al. 2020, Colomer-Poveda, Hortobágyi et al. 2020). TMS involves passing single or 87 paired magnetic pulses over the primary motor cortex (M1) by placing a magnetic coil on the scalp. The magnetic 88 pulse propagates volleys of action potentials along the CST and peripheral motor nerve (Di Lazzaro, Oliviero et al. 89 2004), which in turn causes a motor response in the associated target muscle (Di Lazzaro and Rothwell 2014). 90 The motor response is recorded from the target muscle via EMG and is termed the motor-evoked potential (MEP). 91 The muscle activity generated by TMS is dependent on neuronal excitability in both the M1 and spinal cord, and is 92 typically considered a measure of CSE (Chen 2000, Kobayashi and Pascual-Leone 2003). 93 94 Paired-pulse TMS assess the excitability of intrinsic intracortical connections within the M1 (Di Lazzaro and 95 Ziemann 2014). Depending on the inter-stimulus interval between the conditioning and test pulse, paired-pulses 96 can measure the excitability of the intracortical micro-circuitry of M1 in particular short-interval intracortical inhibition 97 (SICI) (e.g., 2-5ms) and long-interval intracortical inhibition (LICI) (e.g., 100-150ms) as well as the intracortical 98 facilitatory (ICF) circuits (e.g., 8-15ms). Adjustments in SICI have been reported to be critical in the selective 99 activation of muscles and the conditioned MEP increases with increasing force levels (Stinear and Byblow 2003); 100 thus, changes in SICI may occur in a intensity-specific manner following strength training. For this reason, the 101 current study assessed SICI following a single session of either highor low-intensity strength training in an attempt 102 to determine the training intensity effects on modulating SICI as a potential acute neural adaptation to strength 103 training. 104 105 Relatively few studies have examined the corticospinal responses to a single session of strength training, and the 106 existing evidence is conflicting (Brandner, Warmington et al. 2015, Leung, Rantalainen et al. 2015, Latella, Hendy 107 et al. 2016, Nuzzo, Barry et al. 2016, Latella, Goodwill et al. 2019). Increases in CSE have been reported when 108 4 TMS is applied during muscle activity following high-intensity (i.e., heavy-load) strength training of the biceps 109 brachii (Brandner, Warmington et al. 2015, Leung, Rantalainen et al. 2015, Latella, Teo et al. 2017, Mason, Frazer 110 et al. 2019, Colomer-Poveda, Hortobágyi et al. 2020, Ruotsalainen, Ahtiainen et al. 2014), but there is limited 111 evidence for the lower-limb muscles (Ansdell, Brownstein et al. 2020). The inhibitory responses to a single session 112 of strength training are even less well characterized (Leung, Rantalainen et al. 2015, Ruotsalainen, Ahtiainen et 113 al. 2014, Mason, Frazer et al. 2018, Latella, Goodwill et al. 2019, Mason, Frazer et al. 2019), but there is emerging 114 evidence that SICI is reduced by a single session of strength training in the upper-limb (Hendy and Kidgell 2014, 115 Brandner, Warmington et al. 2015, Leung, Rantalainen et al. 2015, Latella, Goodwill et al. 2019). However, the 116 findings are limited and inconsistent (Latella, Teo et al. 2017, Latella, Goodwill et al. 2019) and there is only one 117 study that reported null findings in the lower-limb (Ansdell, Brownstein et al. 2020). Latella et al. (2019) reported 118 that, following heavy-load eccentric strength training of the biceps brachii, the conditioned MEP responses 119 increased for both the SICI and LICI paradigm. However, this is in contrast to previous findings from the same 120 research group which indicated no change in SICI or LICI following heavy-load isotonic training of the biceps brachii 121 (Latella, Teo et al. 2017). More recently, Ansdell, Brownstein et al. (2020) reported that a single session of squat 122 training had no effect on CSE and SICI, but increased spinal excitability as assessed by lumbar-evoked potentials 123 (LEPs). 124 125 Given that strength training is one of the most robust methods for improving muscular fitness, manipulating the 126 acute training variables, such as relative intensity (i.e., percentage of one-repetition maximum), could be a critical 127 determinant of the type (i.e., reduced inhibition) of neural adaptation to strength training. Therefore, determining 128 the neural adaptations to high-intensity and low-intensity strength training appears important. Most previous 129 research has only focused on the acute corticospinal responses to high-intensity strength training of the upper130 limb (Leung, Rantalainen et al. 2015, Latella, Hendy et al. 2016, Nuzzo, Barry et al. 2016, Latella, Goodwill et al. 131 2019), therefore, there is a need to determine the corticospinal responses following both highand low-intensity 132 strength training of the lower-limb. Given that low-intensity compared with high-intensity strength training can also 133 improve muscle strength (Schoenfeld, Ogborn et al. 2017) and because the hypertrophy response to strength 134 training seems to be independent of relative intensity (Lopez, Radaelli et al. 2021), the differences in the increase 135 in muscle strength brought about by lowand high-intensity strength training, may be related to modifications in 136 the corticospinal responses to strength training. 137 138 To address this gap in the literature, two recent studies reported that there is a dose-response relationship between 139 isometric strength training and CSE of the elbow flexors (Colomer-Poveda, Romero-Arenas et al. 2019; Colomer140 Poveda, Romero-Arenas et al. 2020). Of important note is the Colomer-Poveda, Romero-Arenas et al. (2020) study 141 which reported no changes in the intracortical response (SICI or ICF) following strength training at different strength 142 training intensities (Colomer-Poveda, Romero-Arenas et al. 2020). Thus, one of the aims of the current study was 143 to assess the intracortical responses (SICI) following highand low-intensity strength training of the lower-limb. In 144 regards to the two previous intensity-related studies that reported changes in CSE following high-intensity training, 145 5 the type of exercise employed may explain the null finding of no change in CSE following low-intensity strength 146 training. Previously, it has been suggested that dynamic rather than isometric contractions activate the M1 more 147 strongly and sustainably throughout the contraction (Gwin and Ferris 2012). 148 149 As it stands, there is limited evidence on the acute effects of lower-limb strength training on CSE and SICI and 150 there is no experimental data for the effects of low-intensity lower-limb strength training on the corticospinal 151 responses. Understanding the acute neural responses of the lower-limb muscles to strength training will pave the 152 way to prescribe effective and targeted exercise guidelines for the management of neuromuscular pathology of the 153 lower-limbs. This is important because sufficient knee extensor torque is required for the successful completion of 154 many activities of daily living (e.g., locomotion, chair sitting and rising, and stair climbing) and athletic tasks, so it 155 is an important muscle group to study. Therefore, the aim of this study was to identify the acute corticospinal 156 responses (CSE and SICI) following an acute bout of either lowor high-intensity KE strength training. Based upon 157 our previous experiments (Mason, Frazer et al. 2019), where we showed that heavy-load strength training 158 compared to light-load strength training of the elbow flexors modulated SICI in an intensity-specific manner, we 159 hypothesized that high-intensity strength training (85% 1-repetition maximum) would increase CSE and reduce 160 SICI, whilst low-intensity strength training (<30% 1-RM), would increase CSE and have no effect on SICI. 161 162 Methods: 163 164 Experimental Approach and Participants 165 Figure 1 outlines the experimental design. Before commencing the study, participants underwent a familiarization 166 session that involved: (a) anthropometric measurements of height and weight; (b) strength testing to evaluate 167 maximal voluntary isometric strength of the knee extensors (MVC); and (c) exposure to TMS, surface 168 electromyography (sEMG), and peripheral nerve stimulation. After this visit, in a randomized-control design, 169 participants attended the laboratory once, which was separated by seven days from the familiarization session. A 170 purpose-made Excel macro was used to randomize participants to the experimental groups. Participants were 171 randomly allocated to a control group (n = 7, 2 females, 5 males), low-intensity strength training (n = 10, 3 females, 172 7 males) and high-intensity strength training group (n = 11, 4 females, 7 males) that involved a single-bout of 173 strength training of the KE. Participants were selected on a voluntary basis and all experiments were conducted 174 according to the standards established by the Declaration of Helsinki, and the project was approved by the 175 University Human Research Ethics Committee (ID:11882). Twenty-eight healthy participants (9 females and 19 176 males, aged 23 ± 3 years, height 176 ± 11cm and body mass of 73 ± 15kg) took part in this study without any 177 known history of neurological impairment or current physical illness or injuries, and all participants provided 178 informed consent prior to the commencement of the study. Overall, subjects had little or no history of strength 179 training and were included if they had not participated in strength training within the last six months. Participants 180 were screened for contraindication to TMS and strength training (Chipchase, Schabrun et al. 2012). Only one of 181 the participants reported that they had been completing strength training of the KE > 1 day per week two months 182 6 before data collection. Consequently, they were randomly allocated to either the control group or low-intensity 183 strength training group. 184 Insert Figure 1 185 186 Maximum Isometric Strength Testing 187 The order of strength testing (i.e., dynamic and isometric testing) was randomized across participants. Maximum 188 isometric torque (maximum voluntary contraction) of the quadriceps femoris was determined prior to (T0min) and 189 following the training intervention at T5min (Post 5 min), T30min (Post 30 min) and T60min (Post 60 min) using an 190 isokinetic dynamometer (Biodex system 4 Pro, Biodex Medical Systems, Shirley, NY, USA). All participants 191 completed a warm-up that consisted of 5 minutes of cycling on a cycle-ergometer at an intensity of 70% age192 predicted maximum heart rate (± 5 beats·per·min), and five warm-up leg extensions with gradually increasing 193 weight. Participants were placed in a seated position with a trunk-thigh angle of 110°. The axis of the dynamometer 194 was then aligned with the anatomical axis of the knee joint, and the leg was fastened to the dynamometer lever 195 arm using a padded strap positioned 1 cm superior to the malleoli of the ankle. To ensure that the trunk was 196 stabilized during testing, a waist strap and two cross-over shoulder straps were used. During isometric testing, the 197 knee was positioned at a 60° angle and the participant was required to perform three maximal isometric leg 198 extensions for 5 seconds with 2 minutes rest period between each repetition. Verbal instructions and 199 encouragement were provided to ensure that each participant achieved their true MVC. The highest peak torque 200 of the three trials was taken and recorded as the participants MVC torque. Only the dominant limb was tested. 201 202 Dynamic Strength Testing 203 Participants completed a bilateral one-repetition maximum knee extension strength test (1RM) through a full range 204 of motion (Nautilus Nitro® Plus Leg Extension, Vancouver, WA, USA). Prior to commencing the knee extension 205 tests, participants completed a warm up that involved completing 10 repetitions at 50% of their estimated knee 206 extensor 1RM. Following this, participants then completed a single repetition, whereby each single repetition 207 progressed with heavier loads until failure, which was defined as the final load that could be lifted successfully with 208 correct technique where an additional 0.5–5.0 kg could not be successfully lifted. Between each 1RM trial, a 2209 minute recovery period was allocated and, in general, participants took between four to six attempts to determine 210 their 1RM. The maximum weight lifted was then used to calculate the training-intensity for the single session of 211 strength training for both the high-intensity (85% 1RM) and low-intensity (30% 1RM) training groups. 1RM testing 212 was only performed at baseline (T0min). 213 Strength Training Protocol 214 Participants in the high-intensity (relative load-intensity of 1RM) group were required to exercise at 85% 1RM 215 (average load was 67 ± 17 Kg). Participants performed four sets of 6-8 repetitions of bilateral knee extension, 216 separated by 2-minutes rest between sets. Participants in the low-intensity (relative load-intensity) group were 217 required to exercise at 30% 1RM (average load was 24 ± 6 Kg). Participants performed four sets of 30 repetitions 218 separated by 30 seconds rest between sets. The total time to complete the high-intensity training was 9 minutes, 219 7 and it was 6.5 minutes in the low-intensity group. The total load-volume (weight × repetitions) for the high-intensity 220 group was 2,156 ± 533 and 2,836 ± 725 for the low-intensity group, respectively. Participants in the control group 221 were sitting in a chair in the laboratory for 10 minutes. 222 223 Electromyography 224 Surface electromyography (sEMG) was recorded from the right (dominant) rectus femoris muscle using bipolar 225 Ag-AgCl electrodes (Brownstein, Ansdell et al. 2018). The area of electrode placement was shaved to remove fine 226 hair, rubbed with an abrasive skin gel to remove dead skin, and then cleaned with 70% isopropyl alcohol. The site 227 of measurement for the rectus femoris was determined by marking the skin three-fifths of the distance between 228 the anterior superior iliac spine (ASIS) and the upper border of the patella, with an inter-electrode distance (centre 229 to centre) of 20 mm. The reference electrode was placed on the patella to ensure no muscle activity was recorded. 230 sEMG signals were measured with an impedance meter to ensure impedance did not exceed 10 kΩ prior to testing. 231 sEMG signals were amplified (×1,000), bandpass filtered (high pass at 13 hz, low pass at 1,000 Hz), digitized 232 online at 2 kHz for 1 s, recorded and analysed using Powerlab 4/35 (ADInstruments, Bella Vista, Australia). 233 234 Transcranial magnetic stimulation 235 Singleand paired-pulse TMS was delivered over the M1 via a concave double-cone coil using a Magstim 2002 236 magnetic stimulator (Magstim Co., Ltd, Whitland, UK). The junction of the double-cone coil was placed 1–2 cm left 237 of the vertex and oriented to induce posterior-to-anterior cortical current flow. Sites near the estimated centre of 238 the rectus femoris area (motor hotspot) were explored to determine the sites at which the largest MEP amplitude 239 was evoked and active motor threshold (AMT) was established as the intensity at which at least 5 of 10 stimuli 240 produced MEP amplitudes of greater than 200 µV (Kidgell, Stokes et al. 2010) during a low-level isometric 241 contraction. After the single session of strength training, AMT was retested and adjusted if required. To ensure all 242 stimuli were delivered to the optimal motor hotspot throughout testing, the position of the coil was marked. 243 244 All stimuli were delivered during low-level isometric contraction of the KE, which were performed by exerting 10% 245 of their pre-determined MVC torque as indicated by a visual line representing voluntary KE force on a computer 246 monitor connected to an isokinetic dynamometer (Biodex system 4 Pro, Biodex Medical Systems). Root mean 247 square (rms) of the rectus femoris electromyogram (EMG) was obtained 100 ms before the delivery of each TMS 248 stimulus to ensure that there were no changes in pre-stimulus rmsEMG prior to, and following, KE training which 249 may have altered the MEP amplitude. 250 251 Assessment of CSE: Single-pulse TMS-induced MEPs 252 Once AMT was established, ten single-pulse TMS induced MEPs were recorded using 130% AMT before (T0min), 253 post 5 min (T5min), 30 min (T30min) and 60 min (T60min) after the training (Ansdell, Brownstein et al. 2020). Providing 254 10 single-pulse MEPs has been shown to be a reliable number to estimate CSE (Ansdell, Brownstein et al. 2020). 255 Each stimulus was delivered in random intervals every 10 to 12 seconds to avoid stimulus anticipation. The average 256 8 stimulator intensity was 55% of maximal stimulator output (MSO) for high-intensity and low-intensity training and 257 50% MSO for the control group. 258 259 Assessment of Short-Interval Intracortical Inhibition 260 SICI was assessed by a TMS paired-pulse protocol, including 10 stimuli with an interstimulus interval of 3 ms 261 (Brownstein, Ansdell et al. 2018). In this protocol, SICI was assessed by combining a subthreshold conditioning 262 stimulus (70% AMT) with a suprathreshold test stimulus (130% AMT). 263 264 Percutaneous Nerve Stimulation 265 Direct muscle responses were obtained under resting conditions from the right rectus femoris by supra-maximal 266 percutaneous electrical stimulation of the femoral nerve approximately 3-5 cm below the inguinal ligament in the 267 femoral triangle. A digitimer (Hertfordshire. UK) DS7A constant-current electrical stimulator (pulse duration 1 ms) 268 was used to deliver each electrical pulse. The cathode was placed over the femoral nerve in the femoral triangle 269 with the anode positioned between the greater trochanter and iliac crest. An increase in current strength was 270 applied to the femoral nerve until there was no further increase in the amplitude of sEMG response (MMAX). To 271 ensure maximal responses, the current was increased an additional 20% and the average MMAX was obtained from 272 five stimuli, with a period of 6-9 seconds separating each stimulus (Ansdell, Brownstein et al. 2020) 273 274 Data Analysis 275 The peak-to-peak amplitude of MEPs evoked as a result of stimulation was measured in the dominant right rectus 276 femoris muscle contralateral to the cortex being stimulated in the period 10-50 ms after stimulation. MEP 277 amplitudes were analysed (LabChart 8 software, ADInstruments, Australia) after each stimulus was automatically 278 flagged with a cursor, providing peak-to-peak values in µV, averaged and normalized to the maximum compound 279 wave (MMAX), and multiplied by 100. SICI was quantified as the size of the conditioned paired-pulse MEP expressed 280 relative to the size of the unconditioned MEP and multiplied by 100. 281 282 Statistical Analysis 283 The target sample size was based on an a priori calculation, which included the observed effect size from our 284 previous experiments (Mason, Frazer et al. 2019). The number of subjects to be included in the study was 285 computed using an α level of 0.05, a β level of 0.80, and an effect size of 0.8. 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Howatson (2021). "Corticospinal and 609 spinal adaptations to motor skill and resistance training: Potential mechanisms and implications for motor 610 rehabilitation and athletic development." European journal of applied physiology: 1-13. 611 39. Weier, A. T., A. J. Pearce and D. J. Kidgell (2012). "Strength training reduces intracortical inhibition." Acta 612 physiologica 206(2): 109-119. 613 40. Woods, J. J., F. Furbush and B. Bigland-Ritchie (1987). "Evidence for a fatigue-induced reflex inhibition 614 of motoneuron firing rates." Journal of Neurophysiology 58(1): 125-137. 615 616 617 618 619 18 620 621 Figure 1. Experimental design of the study. Post intervention testing was undertaken at three separate time points 622 (T5min, T30min, T60min). 623 624 625 626 627 628 629 630 631 632 633 634 635 636 637 638 639 640 641 642 643 644 Data Collection M-waves Corticospinal excitability SICI KE MVC T0min 10 min T5min T30min T60mIn 19 645 646 Figure 2. Mean change (± 95% Confidence Interval [CI]) for isometric knee extensor torque (N·m) at T5min, T30min, 647 T60min post strength training. 648 649 650 651 652 653 654 655 656 657 658 659 660 20 661 662 Figure 3. Mean change (± 95% CI) in SICI for the trained knee extensors. *Denotes a decrease in SICI from T5min, 663 T30min and T60min compared to the low-intensity (Group × Time effect). 664 665 666 667 668 669 670 671 672 673 674 675 676 677 21 678 Figure 4. Mean change (± 95% CI) in MEP amplitude for the trained knee extensors. ### Denotes a significant 679 increase in MEP at T5min, T30min and T60min compared to the low-intensity and the control group (Group × Time 680 effect). 681 682 683 684 685 686 687 688 689 690 691 692 22 693 694