NeuroMeasure: A Software Package for Quantification of Cortical Motor Maps Using Frameless Stereotaxic Transcranial Magnetic Stimulation.

The recent enhanced sophistication of non-invasive mapping of the human motor cortex using MRI-guided Transcranial Magnetic Stimulation (TMS) techniques, has not been matched by refinement of methods for generating maps from motor evoked potential (MEP) data, or in quantifying map features. This is despite continued interest in understanding cortical reorganization for natural adaptive processes such as skill learning, or in the case of motor recovery, such as after lesion affecting the corticospinal system. With the observation that TMS-MEP map calculation and quantification methods vary, and that no readily available commercial or free software exists, we sought to establish and make freely available a comprehensive software package that advances existing methods, and could be helpful to scientists and clinician-researchers. Therefore, we developed NeuroMeasure, an open source interactive software application for the analysis of TMS motor cortex mapping data collected from Nexstim® and BrainSight®, two commonly used neuronavigation platforms. NeuroMeasure features four key innovations designed to improve motor mapping analysis: de-dimensionalization of the mapping data, fitting a predictive model, reporting measurements to characterize the motor map, and comparing those measurements between datasets. This software provides a powerful and easy to use workflow for characterizing and comparing motor maps generated with neuronavigated TMS. The software can be downloaded on our github page: https://github.com/EdwardsLabNeuroSci/NeuroMeasure. AIM: This paper aims to describe a software platform for quantifying and comparing maps of the human primary motor cortex, using neuronavigated transcranial magnetic stimulation, for the purpose of studying brain plasticity in health and disease.

Clinical improvement with intensive robot-assisted arm training in chronic stroke is unchanged by supplementary tDCS.

BACKGROUND: Intensive robot-assisted arm training in the chronic phase of stroke recovery can lead to clinical improvement. Combinatorial therapeutic approaches are sought to further optimize stroke recovery. Transcranial direct current stimulation (tDCS) is one candidate to combine with robotic training, as transient increases in excitability and improvements in motor behavior have separately been reported. OBJECTIVE: To determine whether tDCS, delivered prior to robotic training, could augment clinical improvement. METHODS: We conducted a dual-site, randomized controlled trial in 82 chronic ischemic stroke patients (inclusion > 6 m post-injury, dominant hemisphere, first stroke; residual hemiparesis) who were split into two groups to receive tDCS (M1-SO montage, anode ipsilesional, 5×7 cm electrodes, 2 mA, 20 mins) or sham tDCS, prior to robotic upper-limb training (12 weeks; 36 sessions; shoulder-elbow robot or wrist robot on alternating sessions). The primary end-point was taken after 12 weeks of training, and assessed with the Upper Extremity Fugl-Meyer impairment scale (FM). Corticomotor conduction was assessed with transcranial magnetic stimulation (TMS). RESULTS: For the combined group (n = 82; post-training) robotic training increased the FM by 7.36 points compared to baseline (p < 0.0001). There was no difference in the FM increase between the tDCS and sham groups (6.97 and 7.73 respectively, p = 0.46). In both groups, clinically meaningful improvement (≥5 points) from baseline was evident in the majority of patients (56/77), was sustained six months later (54/72), and could be attained in severe, moderate and mild baseline hemiparesis. Clinical improvement was associated with increased excitability in the affected hemisphere as assessed by resting motor threshold (pre-post p = 0.029; pre-post 6 months p = 0.029), but not with threshold-adjusted assessment of MEP amplitude (pre-post p = 0.09; pre-post 6 months p = 0.15). Participants with motor evoked potentials were more likely to improve clinically than those without (17/18, 94%, versus 39/59, 66%, p = 0.018). CONCLUSIONS: Our study confirms the benefit of intensive robot-assisted training in stroke recovery, and indicates that conventional tDCS does not confer further advantage to robotic training. We also showed that corticospinal integrity, as assessed by TMS, is a predictor of clinically meaningful response to intensive arm therapy in chronic stroke.

Robotic Arm Rehabilitation in Chronic Stroke Patients With Aphasia May Promote Speech and Language Recovery (but Effect Is Not Enhanced by Supplementary tDCS).

Objective: This study aimed to determine the extent to which robotic arm rehabilitation for chronic stroke may promote recovery of speech and language function in individuals with aphasia. Methods: We prospectively enrolled 17 individuals from a hemiparesis rehabilitation study pairing intensive robot assisted therapy with sham or active tDCS and evaluated their speech (N = 17) and language (N = 9) performance before and after a 12-week (36 session) treatment regimen. Performance changes were evaluated with paired t-tests comparing pre- and post-test measures. There was no speech therapy included in the treatment protocol. Results: Overall, the individuals significantly improved on measures of motor speech production from pre-test to post-test. Of the subset who performed language testing (N = 9), overall aphasia severity on a standardized aphasia battery improved from pre-test baseline to post-test. Active tDCS was not associated with greater gains than sham tDCS. Conclusions: This work indicates the importance of considering approaches to stroke rehabilitation across different domains of impairment, and warrants additional exploration of the possibility that robotic arm motor treatment may enhance rehabilitation for speech and language outcomes. Further investigation into the role of tDCS in the relationship of limb and speech/language rehabilitation is required, as active tDCS did not increase improvements over sham tDCS.

Muscle length effect on corticospinal excitability during maximal concentric, isometric and eccentric contractions of the knee extensors.

NEW FINDINGS: What is the central question of this study? Does sensory input from peripheral mechanoreceptors determine the specific neural control of eccentric contractions? How corticospinal excitability (i.e. muscle responses to motor cortex stimulation) is affected by muscle length has never been investigated during eccentric contractions. What is the main finding and its importance? Muscle length does not influence corticospinal excitability during concentric and isometric maximal contractions, but does during eccentric maximal contractions. This indicates that neural control in eccentric contractions differs from that in concentric and isometric contractions. Neural control of eccentric contractions differs from that of concentric and isometric contractions, but no previous study has compared responses to motor cortex stimulations at long muscle lengths during such contraction types. In this study, we compared the effect of muscle length on corticospinal excitability between maximal concentric, isometric and eccentric contractions of the knee extensors. Twelve men performed 12 maximal concentric, isometric and eccentric voluntary contractions (36 contractions in total), separated by a 5 min rest between contraction types. The 12 contractions for the same contraction type were performed every 10 s, and transcranial magnetic stimulations (first eight contractions) and electrical femoral nerve stimulations (last four contractions) were superimposed alternately at 75 and 100 deg of knee flexion. Average motor evoked potential amplitude, normalized to the maximal M wave amplitude (MEP/M) and cortical silent period duration were calculated for each angle and compared among the contraction types. The MEP/M was lower (-23 and -28%, respectively) during eccentric than both concentric and isometric contractions at 75 deg, but similar between contraction types at 100 deg (P < 0.05). The cortical silent period duration was shorter (-12 and -10%, respectively) during eccentric than both concentric and isometric contractions at 75 deg, but longer (+11 and +9%, respectively) during eccentric contractions at 100 deg (P < 0.05). These results show that corticospinal excitability during eccentric contractions is angle dependent such that cortical inhibitory processes are greater with no alteration of corticospinal excitability at 100 deg, whereas this control is reversed at 75 deg.

Improved grasp function with transcranial direct current stimulation in chronic spinal cord injury.

BACKGROUND: Recovering hand function has important implications for improving independence of patients with tetraplegia after traumatic spinal cord injury (SCI). Transcranial direct current stimulation (tDCS) is a noninvasive neuromodulation technique that has potential to improve motor function. OBJECTIVE: To investigate the effects of one session of 1 mA, 2 mA, and sham anodal tDCS (a-tDCS) in the upper extremity (hand) motor performance (grasp and lease) in patients with chronic cervical SCI. METHODS: Eleven participants with incomplete SCI were randomized to receive 20 minutes of 1 mA, 2 mA, or sham stimulation over the targeted motor cortex over three separated sessions. Hand motor performance was measured by a hand robotic evaluation (kinematics) and the Box and Blocks (BB) test before and after the stimulation period. RESULTS: A significant improvement on the grasp mean to peak speed ratio (GMP) was observed in the 2 mA group (pre: 0.38±0.02; post: 0.43±0.03; mean±SEM; p = 0.031). There was no statistically significant difference in BB test results, however the 2 mA intervention showed a positive trend for improvement. CONCLUSIONS: A single session of 2 mA of a-tDCS showed gains in hand motor function in patients with chronic SCI that were not observed in functional clinical scales. The use of robotic kinematics showed promising results in assessing small changes in motor performance. Further studies are necessary to determine whether tDCS can be an effective long-term rehabilitation strategy for individuals with SCI.

Optimising conservative management of chronic low back pain: study protocol for a randomised controlled trial.

BACKGROUND: Lower back pain is a global health issue affecting approximately 80% of people at some stage in their life. The current literature suggests that any exercise is beneficial for reducing back pain. However, as pain is a subjective evaluation and physical deficits are evident in low back pain, using it as the sole outcome measure to evaluate superiority of an exercise protocol for low back pain treatment is insufficient. The overarching goal of the current clinical trial is to implement two common, conservative intervention approaches and examine their impact on deficits in chronic low back pain. METHODS/DESIGN: Forty participants, 25-45 years old with chronic (>3 months), non-specific low back pain will be recruited. Participants will be randomised to receive either motor control and manual therapy (n = 20) or general strength and conditioning (n = 20) exercise treatments for 6 months. The motor control/manual therapy group will receive twelve 30-min sessions, ten in the first 3 months (one or two per week) and two in the last 3 months. The general exercise group will attend two 1-hour sessions weekly for 3 months, and one or two a week for the following 3 months. Primary outcome measures are average lumbar spine intervertebral disc T2 relaxation time and changes in thickness of the transversus abdominis muscle on a leg lift using magnetic resonance imaging (MRI). Secondary outcomes include muscle size and fat content, vertebral body fat content, intervertebral disc morphology and water diffusion measured by MRI, body composition using dual energy X-ray absorptiometry, physical function through functional tests, changes in corticospinal excitability and cortical motor representation of the spinal muscles using transcranial magnetic stimulation and self-reported measure of pain symptoms, health and disability. Outcome measures will be conducted at baseline, at the 3-month follow-up and at 6 months at the end of intervention. Pain, depressive symptomology and emotions will be captured fortnightly by questionnaires. DISCUSSION: Chronic low back pain is ranked the highest disabling disorder in Australia. The findings of this study will inform clinical practice guidelines to assist with decision-making approaches where outcomes beyond pain are sought for adults with chronic low back pain. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry, ACTRN12615001270505 . Registered on 20 November 2015.

Repetitive Transcranial Magnetic Stimulation of the Brain: Mechanisms from Animal and Experimental Models.

Since the development of transcranial magnetic stimulation (TMS) in the early 1980s, a range of repetitive TMS (rTMS) protocols are now available to modulate neuronal plasticity in clinical and non-clinical populations. However, despite the wide application of rTMS in humans, the mechanisms underlying rTMS-induced plasticity remain uncertain. Animal and in vitro models provide an adjunct method of investigating potential synaptic and non-synaptic mechanisms of rTMS-induced plasticity. This review summarizes in vitro experimental studies, in vivo studies with intact rodents, and preclinical models of selected neurological disorders-Parkinson's disease, depression, and stroke. We suggest that these basic research findings can contribute to the understanding of how rTMS-induced plasticity can be modulated, including novel mechanisms such as neuroprotection and neurogenesis that have significant therapeutic potential.

Construction and Evaluation of Rodent-Specific rTMS Coils.

Rodent models of transcranial magnetic stimulation (TMS) play a crucial role in aiding the understanding of the cellular and molecular mechanisms underlying TMS induced plasticity. Rodent-specific TMS have previously been used to deliver focal stimulation at the cost of stimulus intensity (12 mT). Here we describe two novel TMS coils designed to deliver repetitive TMS (rTMS) at greater stimulation intensities whilst maintaining spatial resolution. Two circular coils (8 mm outer diameter) were constructed with either an air or pure iron-core. Peak magnetic field strength for the air and iron-cores were 90 and 120 mT, respectively, with the iron-core coil exhibiting less focality. Coil temperature and magnetic field stability for the two coils undergoing rTMS, were similar at 1 Hz but varied at 10 Hz. Finite element modeling of 10 Hz rTMS with the iron-core in a simplified rat brain model suggests a peak electric field of 85 and 12.7 V/m, within the skull and the brain, respectively. Delivering 10 Hz rTMS to the motor cortex of anaesthetized rats with the iron-core coil significantly increased motor evoked potential amplitudes immediately after stimulation (n = 4). Our results suggest these novel coils generate modest magnetic and electric fields, capable of altering cortical excitability and provide an alternative method to investigate the mechanisms underlying rTMS-induced plasticity in an experimental setting.

Augmenting Plasticity Induction in Human Motor Cortex by Disinhibition Stimulation.

Cellular studies showed that disinhibition, evoked pharmacologically or by a suitably timed priming stimulus, can augment long-term plasticity (LTP) induction. We demonstrated previously that transcranial magnetic stimulation evokes a period of presumably GABA(B)ergic late cortical disinhibition (LCD) in human primary motor cortex (M1). Here, we hypothesized that, in keeping with cellular studies, LCD can augment LTP-like plasticity in humans. In Experiment 1, patterned repetitive TMS was applied to left M1, consisting of 6 trains (intertrain interval, 8 s) of 4 doublets (interpulse interval equal to individual peak I-wave facilitation, 1.3-1.5 ms) spaced by the individual peak LCD (interdoublet interval (IDI), 200-250 ms). This intervention (total of 48 pulses applied over ∼45 s) increased motor-evoked potential amplitude, a marker of corticospinal excitability, in a right hand muscle by 147% ± 4%. Control experiments showed that IDIs shorter or longer than LCD did not result in LTP-like plasticity. Experiment 2 indicated topographic specificity to the M1 hand region stimulated by TMS and duration of the LTP-like plasticity of 60 min. In conclusion, GABA(B)ergic LCD offers a powerful new approach for augmenting LTP-like plasticity induction in human cortex. We refer to this protocol as disinhibition stimulation (DIS).

Stroke subtype and motor impairment influence contralesional excitability.

OBJECTIVE: The nonlesioned motor cortex (M1NL) is thought to be hyperexcitable in patients with subacute or chronic stroke and offers a promising therapeutic target. However, whether M1NL excitability behaves the same for subcortical and cortical strokes is unknown. The aim of the present study was to determine whether cortical, or purely subcortical, strokes have a different effect on M1NL excitability. METHODS: We looked for correlations between the Fugl-Meyer (FM) score and M1NL resting motor threshold (RMTNL) in 34 stroke survivors classified according to lesion location (cortico-subcortical or purely subcortical). In addition to the FM, the Wolf Motor Score and motor power were measured. RESULTS: FM correlated with RMTNL for subcortical (r = 0.82; p = 0.001) but not for cortical strokes (r = 0.11; p = 0.62). Likewise, Wolf Motor Score (r = -0.62; p = 0.03) and motor power (r = 0.64; p = 0.023) were correlated with RMTNL for the subcortical group, but not for the cortical group. CONCLUSION: We show that the impact on M1NL depends on lesion location and conclude that protocols aimed at reducing M1NL cortical excitability may be worth exploring for subcortical but not for cortical stroke.

Interactive effects of GPI stimulation and levodopa on postural control in Parkinson's disease.

INTRODUCTION: Postural instability is a major source of disability in idiopathic Parkinson's disease (IPD). Deep brain stimulation of the globus pallidus internus (GPI-DBS) improves clinician-rated balance control but there have been few quantitative studies of its interactive effects with levodopa (L-DOPA). The purpose of this study was to compare the short-term and interactive effects of GPI-DBS and L-DOPA on objective measures of postural stability in patients with longstanding IPD. METHODS: Static and dynamic posturography during a whole-body leaning task were performed in 10 IPD patients with bilateral GPI stimulators under the following conditions: untreated (OFF); L-DOPA alone; DBS alone; DBS+L-DOPA, and in 9 healthy Control subjects. Clinical status was assessed using the UPDRS and AIMS Dyskinesia Scale. RESULTS: Static sway was greater in IPD patients in the OFF state compared to the Control subjects and was further increased by L-DOPA and reduced by GPI-DBS. In the dynamic task, L-DOPA had a greater effect than GPI-DBS on improving Start Time, but reduced the spatial accuracy and directional control of the task. When the two therapies were combined, GPI-DBS prevented the L-DOPA induced increase in static sway and improved the accuracy of the dynamic task. CONCLUSION: The findings demonstrate GPI-DBS and L-DOPA have differential effects on temporal and spatial aspects of postural control in IPD and that GPI-DBS counteracts some of the adverse effects of L-DOPA. Further studies on larger numbers of patients with GPI stimulators are required to confirm these findings and to clarify the contribution of dyskinesias to impaired dynamic postural control.

Evidence for an excitatory GABAA response in human motor cortex in idiopathic generalised epilepsy.

PURPOSE: Impaired GABAergic inhibition has been implicated in the pathophysiology of epilepsy. The possibility of a paradoxical excitatory effect of GABA in epilepsy has been suggested, but has not been investigated in vivo. We investigated pre- and post-synaptic GABAergic mechanisms in patients with idiopathic generalised epilepsy (IGE). METHOD: In 10 patients and 12 control subjects we explored short- and long-interval intracortical inhibition (SICI, LICI; post-synaptic GABAA and GABAB-mediated respectively) and long-interval intracortical facilitation (LICF; pre-synaptic disinhibition) using transcranial magnetic stimulation. RESULTS: While post-synaptic GABAB-mediated inhibition was unchanged in IGE (p=0.09), LICF was reduced compared to controls (controls: 141±17% of baseline; untreated patients: 107±12%, p=0.2; treated patients: 79±10%, p=0.003). GABAA-mediated inhibition was reduced in untreated patients (response amplitude 56±4% of baseline vs. 26±6% in controls, p=0.004) and normalised with treatment (37±12%, p=0.5 vs. controls). When measured during LICI, GABAA-mediated inhibition became excitatory in untreated IGE (response amplitude 120±10% of baseline, p=0.017), but not in treated patients. CONCLUSION: Pre- and post-synaptic GABA-mediated inhibitory mechanisms are altered in IGE. The findings lend in vivo support to evidence from experimental models and in vitro studies of human epileptic brain tissue that GABA may have a paradoxical excitatory role in ictogenesis.

Movement-generated afference paired with transcranial magnetic stimulation: an associative stimulation paradigm.

BACKGROUND: A peripheral nerve stimulus can enhance or suppress the evoked response to transcranial magnetic stimulation (TMS) depending on the latency of the preceding peripheral nerve stimulation (PNS) pulse. Similarly, somatosensory afference from the passively moving limb can transiently alter corticomotor excitability, in a phase-dependent manner. The repeated association of PNS with TMS is known to modulate corticomotor excitability; however, it is unknown whether repeated passive-movement associative stimulation (MAS) has similar effects. METHODS: In a proof-of-principal study, using a cross-over design, seven healthy subjects received in separate sessions: (1) TMS (120% of the resting motor threshold-RMT, optimal site for Flexor Carpi Radialis) with muscle at rest; (2) TMS paired with cyclic passive movement during extension cyclic passive movement (400 pairs, 1 Hz), with the intervention order randomly assigned. Normality was tested using the Kolmogorov-Smirnov test, then compared to pre-intervention baseline using repeated measures ANOVA with a Dunnet multiple comparisons test. RESULTS: MAS led to a progressive and significant decrease in the motor evoked potential (MEP) amplitude over the intervention (R(2) = 0.6665, P < 0.0001), which was not evident with TMS alone (R(2) = 0.0068, P = 0.641). Post-intervention excitability reduction, only present with MAS intervention, remained for 20 min (0-10 min = 68.2 ± 4.9%, P < 0.05; 10-20 min = 73.3 ± 9.7%, P < 0.05). CONCLUSION: The association of somatosensory afference from the moving limb with TMS over primary motor cortex in healthy subjects can be used to modulate corticomotor excitability, and may have therapeutic implications.

Modulation of corticomotor excitability after maximal or sustainable-rate repetitive finger movement is impaired in Parkinson's disease and is reversed by levodopa.

OBJECTIVES: In healthy subjects, fatiguing exercises induce a period of post-exercise corticomotor depression (PECD) that is absent in Parkinson's disease (PD). Our objective is to determine the time-course of corticomotor excitability changes following a 10-s repetitive index finger flexion-extension task performed at maximal voluntary rate (MVR) and a slower sustainable rate (MSR) in PD patients OFF and ON levodopa. METHODS: In 11 PD patients and 10 healthy age-matched controls, motor evoked potentials (MEPs) were recorded from the extensor indicis proprius (EIP) and first dorsal interosseous (FDI) muscles of the dominant arm immediately after the two tasks and at 2-min intervals for 10 min. RESULTS: In the OFF condition the PECD was absent in the two test muscles after both the MVR and MSR tasks. In the ON condition finger movement kinematics improved and a period of PECD comparable to that in controls was present after both tasks. CONCLUSION: The absence of PECD in PD subjects off medication indicates a persisting increase in corticomotor excitability after non-fatiguing repetitive finger movement that is reversed by levodopa. SIGNIFICANCE: Dopamine depletion is associated with impaired modulation of corticomotor excitability after non-fatiguing repetitive finger movement.

Improved motor performance in chronic spinal cord injury following upper-limb robotic training.

BACKGROUND: Recovering upper-limb motor function has important implications for improving independence of patients with tetraplegia after traumatic spinal cord injury (SCI). OBJECTIVE: To evaluate the feasibility, safety and effectiveness of robotic-assisted training of upper limb in a chronic SCI population. METHODS: A total of 10 chronic tetraplegic SCI patients (C4 to C6 level of injury, American Spinal Injury Association Impairment Scale, A to D) participated in a 6-week wrist-robot training protocol (1 hour/day 3 times/week). The following outcome measures were recorded at baseline and after the robotic training: a) motor performance, assessed by robot-measured kinematics, b) corticospinal excitability measured by transcranial magnetic stimulation (TMS), and c) changes in clinical scales: motor strength (Upper extremity motor score), pain level (Visual Analog Scale) and spasticity (Modified Ashworth scale). RESULTS: No adverse effects were observed during or after the robotic training. Statistically significant improvements were found in motor performance kinematics: aim (pre 1.17 ± 0.11 raduans, post 1.03 ± 0.08 raduans, p = 0.03) and smoothness of movement (pre 0.26 ± 0.03, post 0.31 ± 0.02, p = 0.03). These changes were not accompanied by changes in upper-extremity muscle strength or corticospinal excitability. No changes in pain or spasticity were found. CONCLUSIONS: Robotic-assisted training of the upper limb over six weeks is a feasible and safe intervention that can enhance movement kinematics without negatively affecting pain or spasticity in chronic SCI. In addition, robot-assisted devices are an excellent tool to quantify motor performance (kinematics) and can be used to sensitively measure changes after a given rehabilitative intervention.

Clinical and posturographic correlates of falling in Parkinson's disease.

Various clinical tests and balance scales have been used to assess postural stability and the risk of falling in patients with idiopathic Parkinson's disease (IPD). Quantitative posturography allows a more objective assessment but the findings in previous studies have been inconsistent and few studies have investigated which posturographic measures correlate best with a history of falling. The purpose of this study was to determine the efficacy of clinical tests, balance scales, and stable-platform posturography in detecting postural instability and discriminating between fallers and non-fallers in a home-dwelling PD cohort. Forty-eight PD subjects (Hoehn & Yahr stage 1-3) and 17 age-matched controls had the following assessments: Activities-specific Balance Confidence scale, Berg Balance Scale, Unified Parkinson's Disease Rating Scale (UPDRS) (motor), pull-test, timed up-and-go, static posturography, and dynamic posturography to assess multidirectional leaning balance. Of the clinical assessments, all but the pull-test were closely correlated with a history of falling. Static posturography discriminated between PD fallers and controls but not between PD fallers and non-fallers, whereas dynamic posturography (reaction time, velocity, and target hit-time) also discriminated between fallers and non-fallers. Our findings suggest that this combination of clinical and posturographic measures would be useful in the prospective assessment of falls risk in PD patients. A further prospective study is now required to assess their predictive value. © 2013 Movement Disorder Society.

Inverse correlation between resting motor threshold and corticomotor excitability after static magnetic stimulation of human motor cortex.

BACKGROUND: High-strength static magnetic field stimulation (SMS) results in a period of reduced corticomotor excitability that may be mediated through a decrease in membrane excitability. OBJECTIVE: As resting motor threshold (RMT) is thought to reflect membrane excitability, we hypothesized that SMS may increase RMT and that there would be an inverse relationship between RMT and motor-evoked potential (MEP) amplitude. METHODS: Ten healthy subjects (aged 20-29; 4 females) participated in a double-blinded crossover design comparing MEP amplitude and RMT before and after a 15-min period of SMS or sham stimulation over primary motor cortex (M1). RESULTS: MEP amplitude was initially significantly reduced post-SMS (∼20%), and returned to baseline by 6 min post-intervention. MEP amplitude and RMT were inversely correlated (r(2) = 0.924; P = 0.001). Sham stimulation had no effect on MEP amplitude (P = 0.969) or RMT (P = 0.549). CONCLUSION: After SMS, corticomotor excitability is transiently reduced in association with a correlated modulation of RMT. SMS after effects may be mediated in part by a reduction in membrane excitability, suggesting a possible role for non-synaptic (intrinsic) plasticity mechanisms.

Conditioning the cortical silent period with paired transcranial magnetic stimulation.

BACKGROUND: A single supra-threshold pulse of transcranial magnetic stimulation (TMS) over human motor cortex elicits multiple descending volleys (I-waves) that generate a motor evoked potential (MEP) followed by a period of electromyographic silence in the tonically contracted target muscle (silent period; SP). A sub-threshold conditioning stimulus (CS) delivered at inter-pulse intervals (IPIs) of 1-5 ms after a supra-threshold test stimulus (TS) conditions I-waves elicited by TS and can increase MEP amplitude (short-interval intracortical facilitation; SICF), however its effect on the SP remains unknown. OBJECTIVE: We investigated whether it is possible to modulate the SP resulting from a TS by delivering a sub-threshold CS 1-5 ms later. METHODS: Paired-pulse TMS was delivered while subjects performed slight contraction of the first dorsal interosseous muscle. SICF and SP duration were measured at each IPI and compared to amplitude-matched MEPs evoked by single-pulse TMS. RESULTS: Paired stimulation at IPI 2-5 ms prolonged the SP by 21 ± 3% (P < 0.001) but had no effect on MEP amplitude. At shorter IPIs the CS increased MEP amplitude (by 170 ± 31%), but the SP was not prolonged when compared to an amplitude-matched single-pulse stimulus. CONCLUSION: The SP can be modified by a CS applied during the early phase of its genesis. We suggest that this is in keeping with an early GABAA contribution to the SP, and it is possible that this new conditioning paradigm may offer another means for probing the excitability of cortical inhibitory networks in human motor cortex.