Human corticospinal-motoneuronal output is reduced with 5-HT2 receptor antagonism

2021 ◽  
Author(s):  
Jacob R Thorstensen ◽  
Janet Louise Taylor ◽  
Justin J Kavanagh
Keyword(s):  
Repeated Measures ◽  
Biceps Brachii ◽  
Motor Evoked Potentials ◽  
Silent Period ◽  
Human Movement ◽  
Moderate Intensity ◽  
Response Curves ◽  
Stimulus Response ◽  
Repeated Measures Design ◽  
Double Blinded

Animal models indicate that serotonin (5-HT) release onto motoneurons facilitates motor output, particularly during strong motor activities. However, evidence for 5-HT effects during human movement are limited. This study examined how antagonism of the 5-HT2 receptor, which is a 5-HT receptor that promotes motoneuron excitability, affects human movement. Ten healthy participants (24.2 ± 1.9 yr) ingested 8 mg of cyproheptadine (competitive 5-HT2 antagonist) in a double-blinded, placebo-controlled, repeated-measures design. Transcranial magnetic stimulation (TMS) of the motor cortex was used to elicit motor evoked potentials (MEPs) from biceps brachii. First, stimulus-response curves (90-160% active motor threshold) were obtained during very weak elbow flexions (10% of maximal). Second, to determine if 5-HT effects are scaled to the intensity of muscle contraction, TMS at a fixed intensity was applied during elbow flexions of 20, 40, 60, 80 and 100% of maximal. Cyproheptadine reduced the size of MEPs across the stimulus-response curves (P = 0.045). Notably, MEP amplitude was 22.3% smaller for the cyproheptadine condition for the strongest TMS intensity. In addition, cyproheptadine reduced maximal torque (P = 0.045), lengthened the biceps silent period during maximal elbow flexions (P = 0.037), and reduced superimposed twitch amplitude during moderate-intensity elbow flexions (P = 0.035). This study presents novel evidence that 5-HT2 receptors influence corticospinal-motoneuronal output, which was particularly evident when a large number of descending inputs to motoneurons were active. While it is likely that antagonism of 5-HT2 receptors reduces motoneuron gain to ionotropic inputs, supraspinal mechanisms may have also contributed to the study findings.

Reproducible Measurement of Human Motoneuron Excitability With Magnetic Stimulation of the Corticospinal Tract

2009 ◽  
Vol 102 (1) ◽  
pp. 606-613 ◽  
Author(s):  
Peter G. Martin ◽  
Anna L. Hudson ◽  
Simon C. Gandevia ◽  
Janet L. Taylor
Keyword(s):  
Magnetic Stimulation ◽  
Corticospinal Tract ◽  
Motor Evoked Potentials ◽  
Compound Action Potential ◽  
Maximal Response ◽  
Response Curves ◽  
Stimulus Response ◽  
Maximal Output ◽  
Voluntary Contractions ◽  
Stimulation Of

It is difficult to test responses of human motoneurons in a controlled way or to make longitudinal assessments of adaptive changes at the motoneuron level. These studies assessed the reliability of responses produced by magnetic stimulation of the corticospinal tract. Cervicomedullary motor evoked potentials (CMEPs) were recorded in the first dorsal interosseus (FDI) on 2 separate days. On each day, four sets of stimuli were delivered at the maximal output of the stimulator, with the final two sets ≥10 min after the initial sets. Sets of stimuli were also delivered at different stimulus intensities to obtain stimulus-response curves. In addition, on the second day, responses at different stimulus intensities were evoked during weak voluntary contractions. Responses were normalized to the maximal muscle compound action potential ( Mmax). CMEPs evoked in the relaxed FDI were small, even when stimulus intensity was maximal (3.6 ± 2.5% Mmax) but much larger during a weak contraction (e.g., 26.2 ± 10.2% Mmax). CMEPs evoked in the relaxed muscle at the maximal output of the stimulator were highly reproducible both within (ICC = 0.83, session 1; ICC = 0.87, session 2) and between sessions (ICC = 0.87). ICCs for parameters of the input-output curves, which included measures of motor threshold, slope, and maximal response size, ranged between 0.87 and 0.62. These results suggest that responses to magnetic stimulation of the corticospinal tract can be assessed in relaxation and contraction and can be reliably obtained for longitudinal studies of motoneuronal excitability.

scholarly journals Global Corticospinal Excitability as Assessed in A Non-Exercised Upper Limb Muscle Compared Between Concentric and Eccentric Modes of Leg Cycling

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Joel A. Walsh ◽  
Paul J. Stapley ◽  
Jonathan B. H. Shemmell ◽  
Romuald Lepers ◽  
Darryl J. McAndrew
Keyword(s):  
Perceived Exertion ◽  
Motor Evoked Potentials ◽  
Corticospinal Excitability ◽  
Moderate Intensity ◽  
Response Curves ◽  
Large Variability ◽  
Physiological Variables ◽  
Leg Cycling ◽  
First Dorsal Interosseous Muscle ◽  
The Right

AbstractThis study investigated the effects of eccentric (ECC) and concentric (CON) semi-recumbent leg cycling on global corticospinal excitability (CSE), assessed through the activity of a non-exercised hand muscle. Thirteen healthy male adults completed two 30-min bouts of moderate intensity ECC and CON recumbent cycling on separate days. Power output (POutput), heart rate (HR) and cadence were monitored during cycling. Global CSE was assessed using transcranial magnetic stimulation to elicit motor-evoked potentials (MEP) in the right first dorsal interosseous muscle before (‘Pre’), interleaved (at 10 and 20 mins, t10 and t20, respectively), immediately after (post, P0), and 30-min post exercise (P30). Participants briefly stopped pedalling (no more than 60 s) while stimulation was applied at the t10 and t20 time-points of cycling. Mean POutput, and rate of perceived exertion (RPE) did not differ between ECC and CON cycling and HR was significantly lower during ECC cycling (P = 0.01). Group mean MEP amplitudes were not significantly different between ECC and CON cycling at P0, t10, t20, and P30 and CON (at P > 0.05). Individual participant ratios of POutput and MEP amplitude showed large variability across the two modes of cycling, as did changes in slope of stimulus-response curves. These results suggest that compared to ‘Pre’ values, group mean CSE is not significantly affected by low-moderate intensity leg cycling in both modes. However, POutput and CSE show wide inter-participant variability which has implications for individual neural responses to CON and ECC cycling and rates of adaptation to a novel (ECC) mode. The study of CSE should therefore be analysed for each participant individually in relation to relevant physiological variables and account for familiarisation to semi-recumbent ECC leg cycling.

Severe hypoxia affects exercise performance independently of afferent feedback and peripheral fatigue

2012 ◽  
Vol 112 (8) ◽  
pp. 1335-1344 ◽  
Author(s):  
Guillaume Y. Millet ◽  
Makii Muthalib ◽  
Marc Jubeau ◽  
Paul B. Laursen ◽  
Kazunori Nosaka
Keyword(s):  
Biceps Brachii ◽  
Motor Evoked Potentials ◽  
Silent Period ◽  
Afferent Feedback ◽  
Cortical Inhibition ◽  
Severe Hypoxia ◽  
Peripheral Fatigue ◽  
M Wave ◽  
Functional Changes ◽  
Performance Reduction

To test the hypothesis that hypoxia centrally affects performance independently of afferent feedback and peripheral fatigue, we conducted two experiments under complete vascular occlusion of the exercising muscle under different systemic O2 environmental conditions. In experiment 1, 12 subjects performed repeated submaximal isometric contractions of the elbow flexor to exhaustion (RCTE) with inspired O2 fraction fixed at 9% (severe hypoxia, SevHyp), 14% (moderate hypoxia, ModHyp), 21% (normoxia, Norm), or 30% (hyperoxia, Hyper). The number of contractions (performance), muscle (biceps brachii), and prefrontal near-infrared spectroscopy (NIRS) parameters and high-frequency paired-pulse (PS100) evoked responses to electrical muscle stimulation were monitored. In experiment 2, 10 subjects performed another RCTE in SevHyp and Norm conditions in which the number of contractions, biceps brachii electromyography responses to electrical nerve stimulation (M wave), and transcranial magnetic stimulation responses (motor-evoked potentials, MEP, and cortical silent period, CSP) were recorded. Performance during RCTE was significantly reduced by 10–15% in SevHyp (arterial O2 saturation, SpO2 = ∼75%) compared with ModHyp (SpO2 = ∼90%) or Norm/Hyper (SpO2 > 97%). Performance reduction in SevHyp occurred despite similar 1) metabolic (muscle NIRS parameters) and functional (changes in PS100 and M wave) muscle states and 2) MEP and CSP responses, suggesting comparable corticospinal excitability and spinal and cortical inhibition between SevHyp and Norm. It is concluded that, in SevHyp, performance and central drive can be altered independently of afferent feedback and peripheral fatigue. It is concluded that submaximal performance in SevHyp is partly reduced by a mechanism related directly to brain oxygenation.

scholarly journals Effects of Exercise Intensity on Acute Circulating Molecular Responses Poststroke

2020 ◽  
Vol 34 (3) ◽  
pp. 222-234
Author(s):  
Pierce Boyne ◽  
Colleen Meyrose ◽  
Jennifer Westover ◽  
Dustyn Whitesel ◽  
Kristal Hatter ◽  
...  
Keyword(s):  
Growth Factor ◽  
Exercise Intensity ◽  
Gait Speed ◽  
Repeated Measures ◽  
Chronic Stroke ◽  
Moderate Intensity ◽  
Molecular Response ◽  
Vigorous Exercise ◽  
Molecular Responses ◽  
Repeated Measures Design

Background. Exercise intensity can influence functional recovery after stroke, but the mechanisms remain poorly understood. Objective. In chronic stroke, an intensity-dependent increase in circulating brain-derived neurotrophic factor (BDNF) was previously found during vigorous exercise. Using the same serum samples, this study tested acute effects of exercise intensity on other circulating molecules related to neuroplasticity, including vascular-endothelial growth factor (VEGF), insulin-like growth factor-1 (IGF1), and cortisol, with some updated analyses involving BDNF. Methods. Using a repeated-measures design, 16 participants with chronic stroke performed 3 exercise protocols in random order: treadmill high-intensity interval training (HIT-treadmill), seated-stepper HIT (HIT-stepper), and treadmill moderate-intensity continuous exercise (MCT-treadmill). Serum molecular changes were compared between protocols. Mediation and effect modification analyses were also performed. Results. VEGF significantly increased during HIT-treadmill, IGF1 increased during both HIT protocols and cortisol nonsignificantly decreased during each protocol. VEGF response was significantly greater for HIT-treadmill versus MCT-treadmill when controlling for baseline. Blood lactate positively mediated the effect of HIT on BDNF and cortisol. Peak treadmill speed positively mediated effects on BDNF and VEGF. Participants with comfortable gait speed ≥0.4 m/s had significantly lower VEGF and higher IGF1 responses, with a lower cortisol response during MCT-treadmill. Conclusions. BDNF and VEGF are promising serum molecules to include in future studies testing intensity-dependent mechanisms of exercise on neurologic recovery. Fast training speed and anaerobic intensity appear to be critical ingredients for eliciting these molecular responses. Serum molecular response differences between gait speed subgroups provide a possible biologic basis for previously observed differences in training responsiveness.

scholarly journals Stimulus Intensity Affects Variability of Motor Evoked Responses of the Non-Paretic, but Not Paretic Tibialis Anterior Muscle in Stroke

2020 ◽  
Vol 10 (5) ◽  
pp. 297
Author(s):  
Anjali Sivaramakrishnan ◽  
Sangeetha Madhavan
Keyword(s):  
Stimulus Intensity ◽  
Tibialis Anterior ◽  
Motor Evoked Potentials ◽  
Tibialis Anterior Muscle ◽  
Silent Period ◽  
Stimulus Response ◽  
Coefficients Of Variation ◽  
Magnetic Stimulus ◽  
Active Motor ◽  
Selection Of

Background: Transcranial magnetic stimulus induced motor evoked potentials (MEPs) are quantified either with a single suprathreshold stimulus or using a stimulus response curve. Here, we explored variability in MEPs influenced by different stimulus intensities for the tibialis anterior muscle in stroke. Methods: MEPs for the paretic and non-paretic tibialis anterior (TA) muscle representations were collected from 26 participants with stroke at seven intensities. Variability of MEP parameters was examined with coefficients of variation (CV). Results: CV for the non-paretic TA MEP amplitude and area was significantly lower at 130% and 140% active motor threshold (AMT). CV for the paretic TA MEP amplitude and area did not vary with intensity. CV of MEP latency decreased with higher intensities for both muscles. CV of the silent period decreased with higher intensity for the non-paretic TA, but was in reverse for the paretic TA. Conclusion: We recommend a stimulus intensity of greater than 130% AMT to reduce variability for the non-paretic TA. The stimulus intensity did not affect the MEP variability of the paretic TA. Variability of MEPs is affected by intensity and side tested (paretic and non-paretic), suggesting careful selection of experimental parameters for testing.

Abstract 73: Neurophysiology Of Ipsilateral Corticomotor Projections After Perinatal Stroke

Stroke ◽  
2013 ◽  
Vol 44 (suppl_1) ◽  
Author(s):  
Omar Damji ◽  
Oleg Kotsovsky ◽  
Robert Chen ◽  
Adam Kirton
Keyword(s):  
Developmental Plasticity ◽  
Motor Evoked Potentials ◽  
Intracortical Inhibition ◽  
Response Curves ◽  
Perinatal Stroke ◽  
Motor Disability ◽  
Stimulus Response ◽  
Active Motor ◽  
Stroke Type ◽  
Cortical Physiology

Objectives: Perinatal stroke (PS) causes most hemiparetic cerebral palsy. Persistence of ipsilateral corticomotor connections from unlesioned hemisphere to affected hand are established. Their neurophysiology is not understood and developmental plasticity models suggest they are a therapeutic target. We hypothesized that ipsi projections have distinct neurophysiology that correlates with motor disability. Methods: Children 6-18 years with PS (arterial or PVI) and hemiparesis were recruited (Alberta Perinatal Stroke Project). Transcranial magnetic stimulation (TMS) protocols were applied to the non-lesioned M1. Outcomes included rest motor thresholds and bilateral stimulus response curves (SRC). Paired pulse TMS at 2 and 10 ms (90% active motor threshold conditioning) explored short-latency intracortical inhibition (SICI) and intracortical facilitation (ICF). Ipsi motor evoked potentials (MEPs) were quantified (≥0.05mV at 120% RMT in ≥5/20 trials). Motor outcomes were Assisting Hand (AHA) and Melbourne (MA) assessments. Ipsi physiology was compared to contra and motor outcome (t-test, (rm)ANOVA). Safety and tolerability was assessed. Results: Of 35 children (20 male; 55% arterial, 45% PVI), 14 (40%) met ipsi criteria. Presence of ipsi projections correlated with motor disability (AHA, p=0.03, MA p=0.10) but not stroke type. Ipsi intensity correlated with AHA (r=-0.58; p=0.004) and MA (r=-0.45; p=0.013). Ipsi SRC slope was lower than contra (p=0.01). SICI (contra -38.5%, ipsi -30.7%; p<0.05) and ICF (contra +15.4%, ipsi +23.1%; p<0.05) were present and differed between sides (p= 0.004). Procedures were well tolerated. Conclusions: Cortical physiology of ipsilateral projections can be measured in children with PS. Differences between ipsi and contralateral physiology may be relevant central therapeutic targets.

Silent period to transcranial magnetic stimulation: construction and properties of stimulus–response curves in healthy volunteers

2005 ◽  
Vol 163 (1) ◽  
pp. 21-31 ◽  
Author(s):  
V. K. Kimiskidis ◽  
S. Papagiannopoulos ◽  
K. Sotirakoglou ◽  
D. A. Kazis ◽  
A. Kazis ◽  
...  
Keyword(s):  
Transcranial Magnetic Stimulation ◽  
Healthy Volunteers ◽  
Magnetic Stimulation ◽  
Silent Period ◽  
Response Curves ◽  
Stimulus Response

Diazepam Tolerance Effects on Vestibular Function Testing, Part II: Vestibulo-Ocular Reflex Parameters during Rotational Testing

2005 ◽  
Vol 114 (9) ◽  
pp. 722-729 ◽  
Author(s):  
Patricia A. Blau ◽  
Nathan Schwade ◽  
Peter Roland
Keyword(s):  
Repeated Measures ◽  
Statistical Significance ◽  
Vestibular Function ◽  
Normal Male ◽  
Repeated Measures Design ◽  
Ocular Reflex ◽  
Normal Ranges ◽  
Vestibulo Ocular Reflex ◽  
Reflex Gain ◽  
Double Blinded

Objectives: The purpose of this prospective study was to determine whether clinical doses of diazepam (DZ; 10 mg/d) administered for 14 days result in tolerance as measured by the sinuosidal harmonic acceleration (SHA) rotational test. It has been shown that repeated dosing with DZ leads to accumulation and tolerance in outcome measures that assess memory, sedation, and psychomotor tasks. Methods: In a double-blinded, repeated-measures design, 30 normal male subjects who ranged in age from 20 to 36 years were randomly assigned to a placebo group or a DZ group and participated in 6 SHA rotational sessions over a 2-week period. Analysis of drug-placebo differences in percent change from baseline was performed with a 1-way analysis of variance. Results: Vestibulo-ocular reflex gain and phase frequencies at 0.01, 0.02, 0.04, and 0.08 Hz were significant (p < .05) for treatment group. No significant effect was observed for gain and phase frequency at 0.16 Hz — a finding that indicates selective effects on different central nervous system mechanisms. There was no statistical significance for time. Conclusions: Clinically, the DZ subjects' scores remained within the normal ranges for vestibulo-ocular phase and gain, suggesting that patients in whom drug cessation is problematic may not have to discontinue DZ before testing with the SHA rotational system.

Diazepam Tolerance Effects on Vestibular Function Testing, Part I: Saccadic Parameters during Electronystagmography

2005 ◽  
Vol 114 (8) ◽  
pp. 621-628 ◽  
Author(s):  
Patricia A. Blau ◽  
Nathan Schwade ◽  
Peter Roland
Keyword(s):  
Repeated Measures ◽  
Vestibular Function ◽  
Saccadic Eye Movements ◽  
Saccadic Latency ◽  
Treatment Groups ◽  
Repeated Measures Design ◽  
Vestibular Symptoms ◽  
Double Blinded ◽  
Changes Over Time ◽  
Eye Velocity

Objectives: Benzodiazepines, particularly diazepam (DZ), are used in clinical practice to suppress acute vestibular symptoms. There have been limited studies looking at the effects of tolerance to DZ on parameters designed to measure the integrity of the vestibular system and its interaction with the oculomotor and balance systems. Methods: In a double-blinded, repeated-measures design, we randomized 30 young healthy men into one of two treatment groups (diazepam and placebo) and assessed with electro-oculography the effects of clinical divided doses of DZ on saccadic eye movements and sedation over 16 days. Results: Only sedation and saccadic latency were significant (p < .05) for treatment group, indicating selective effects on different central nervous system mechanisms. No significant effect for time was seen in any of the variables measured. Bonferroni t-test comparisons of the DZ group among 3 days were significant (p < .017) between baseline and day 3 for saccadic latency and accuracy and between day 3 and day 16 for self-ratings of sedation. Conclusions: Saccadic latency and accuracy and sedation ratings appear to be more sensitive to changes over time and less affected by subject variability than saccadic eye velocity. It remains questionable whether patients who have been on DZ for acute or extended periods of time need to discontinue the drug 48 hours before testing.

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