Different descending pathways mediate early and late portions of lower limb responses to transcranial magnetic stimulation.

Although recent studies in nonhuman primates have provided evidence that transcranial magnetic stimulation (TMS) activates cells within the reticular formation, it remains unclear whether descending brain stem projections contribute to the generation of TMS-induced motor evoked potentials (MEPs) in skeletal muscles. We compared MEPs in muscles with extensive direct corticomotoneuronal input (first dorsal interosseous) versus a prominent role in postural control (gastrocnemius) to determine whether the amplitudes of early and late MEPs were differentially modulated by cortical suppression. Suprathreshold TMS was applied with and without a preceding suprathreshold TMS pulse at two interstimulus intervals (50 and 80 ms). H reflexes in target muscles were also tested with and without TMS conditioning. Early and late gastrocnemius MEPs were differentially modulated by cortical inhibition, the amplitude of the early MEP being significantly reduced by cortical suppression and the late MEP facilitated. The amplitude of H reflexes in the gastrocnemius was reduced within the cortical silent period. Early MEPs in the first dorsal interosseous were also reduced during the silent period, but late MEPs were unaffected. Independent modulation of early and late MEPs in the gastrocnemius muscle supports the idea that the MEP is generated by multiple descending pathways. Suppression of the early MEP is consistent with transmission along the fast-conducting corticospinal tract, whereas facilitation of the late MEP suggests transmission along a corticofugal, potentially cortico-reticulospinal, pathway. Accordingly, differences in late MEP modulation between the first dorsal interosseous and gastrocnemius reflect an increased role of corticofugal pathways in the control of postural muscles.NEW & NOTEWORTHY Early and late portions of the response to transcranial magnetic stimulation (TMS) in a lower limb postural muscle are modulated independently by cortical suppression, late motor evoked potentials (MEPs) being facilitated during cortical inhibition. These results suggest a cortico-brain stem transmission pathway for late portions of the TMS-induced MEP.

Are ipsilateral motor evoked potentials subject to intracortical inhibition?

Paired-pulse transcranial magnetic stimulation (TMS) can be used to examine intracortical inhibition in primary motor cortex (M1), termed short-interval intracortical inhibition (SICI). To our knowledge, SICI has only been demonstrated in contralateral motor evoked potentials (MEPs). Ipsilateral MEPs (iMEPs) are assumed to reflect excitability of an uncrossed oligosynaptic pathway, and can sometimes be evoked in proximal upper-limb muscles using high-intensity TMS. We examined whether iMEPs in the biceps brachii (BB) would be suppressed by subthreshold conditioning, therefore demonstrating SICI of iMEPs. TMS was delivered to the dominant M1 to evoke conditioned (C) and nonconditioned (NC) iMEPs in the nondominant BB of healthy participants during weak bilateral elbow flexion. The conditioning stimulus intensities tested were 85%, 100%, and 115% of active motor threshold (AMT), at 2 ms and 4 ms interstimulus intervals (ISI). The iMEP ratio (C/NC) was calculated for each condition to assess the amount of inhibition. Inhibition of iMEPs was present at 2 ms ISI with 100% and 115% AMT (bothP< 0.03), mediated by a reduction in persistence and size (allP< 0.05). To our knowledge, this is the first demonstration of SICI of iMEPs. This technique may be useful as a tool to better understand the role of ipsilateral M1 during functional motor tasks.

Neurophysiological and behavioural effects of dual-hemisphere transcranial direct current stimulation on the proximal upper limb.

Dual-hemisphere transcranial direct current stimulation over the primary motor cortex (M1-M1 tDCS) is assumed to modulate neural excitability in a polarity-dependent manner and improve motor performance of the hand. In the proximal upper limb, the neurophysiological and behavioural after-effects of M1-M1 tDCS are not well known. This study investigated the after-effects of M1-M1 tDCS on contralateral, ipsilateral and transcallosal excitability to the proximal upper limb muscle biceps brachii (BB). Circle tracing was used to assess motor performance before and after tDCS as this task requires coordination of proximal and distal musculature. Sixteen healthy right-handed adults participated in the study, each receiving M1-M1 tDCS (1 mA, 15 min) or sham tDCS in separate sessions. The anode was positioned over right M1 and cathode over left M1. M1-M1 tDCS suppressed transcallosal inhibition from the M1 under the cathode (P < 0.045). No other neurophysiologic or behavioural effects were observed (P > 0.6). The study provides important information regarding inconsistent neurophysiological and behavioural changes following tDCS that have implications for future tDCS research on the motor system.

Delayed grip relaxation and altered modulation of intracortical inhibition with aging.

Grip relaxation is a voluntary action that requires an increase in short-interval intracortical inhibition (SICI) in healthy young adults, rather than a simple termination of excitatory drive. The way aging affects this voluntary inhibitory action and timing of grip relaxation is currently unknown. The objective of this study was to examine aging-related delays in grip relaxation and SICI modulation for the flexor digitorum superficialis muscle during grip relaxation. The main finding was that young adults increased SICI to relax their grips, whereas older adults did not increase SICI with a prolonged grip relaxation time (p < 0.05 for both SICI modulation and grip relaxation time). A secondary experiment showed that both young and older adults did not change H reflex excitability during grip relaxation. Our data suggest that grip relaxation is mediated by increased cortical inhibitory output in young adults, and aging-related impairment in increasing cortical inhibitory output may hamper timely cessation of muscle activity. Our data also suggest a lesser role of the spinal circuits in grip muscle relaxation. This knowledge may contribute to understanding of aging-related movement deterioration and development of interventions for improving modulation of SICI to improve muscle relaxation and movement coordination.

Effects of a Single Session of High Intensity Interval Treadmill Training on Corticomotor Excitability following Stroke: Implications for Therapy.

Objective. High intensity interval treadmill training (HIITT) has been gaining popularity for gait rehabilitation after stroke. In this study, we examined the changes in excitability of the lower limb motor cortical representation (M1) in chronic stroke survivors following a single session of HIITT. We also determined whether exercise-induced changes in excitability could be modulated by transcranial direct current stimulation (tDCS) enhanced with a paretic ankle skill acquisition task. Methods. Eleven individuals with chronic stroke participated in two 40-minute treadmill-training sessions: HIITT alone and HITT preceded by anodal tDCS enhanced with a skill acquisition task (e-tDCS+HIITT). Transcranial magnetic stimulation (TMS) was used to assess corticomotor excitability of paretic and nonparetic tibialis anterior (TA) muscles. Results. HIIT alone reduced paretic TA M1 excitability in 7 of 11 participants by ≥ 10%. e-tDCS+HIITT increased paretic TA M1 excitability and decreased nonparetic TA M1 excitability. Conclusions. HIITT suppresses corticomotor excitability in some people with chronic stroke. When HIITT is preceded by tDCS in combination with a skill acquisition task, the asymmetry of between-hemisphere corticomotor excitability is reduced. Significance. This study provides preliminary data indicating that the cardiovascular benefits of HIITT may be achieved without suppressing motor excitability in some stroke survivors.

A dissociation between propriospinal facilitation and inhibition after bilateral transcranial direct current stimulation.

Propriospinal premotoneurons (PN) are essential for accurate control of the upper limb. They receive bilateral input from premotor (PM) and primary motor (M1) cortices. In humans, excitability of PNs can be estimated from motor-evoked potentials (MEPs) by pairing a descending volley using transcranial magnetic stimulation (TMS) to summate with an ascending volley from peripheral nerve stimulation at the C3-C4 level of the spinal cord. Transcranial direct current stimulation (tDCS) alters excitability of cortical and subcortical areas. A recent study demonstrated that cathodal tDCS can suppress facilitatory (FAC) and inhibitory (INH) components of PN excitability, presumably via effects on corticoreticulospinal neurons (Bradnam LV, Stinear CM, Lewis GN, Byblow WD. J Neurophysiol 103: 2382-2389, 2010). The present study investigated the effects of bilateral tDCS with healthy subjects. The cathode was placed over left dorsal PM or M1 and the anode over right M1 in separate sessions (PM-M1, M1-M1, or Sham). TMS of right M1 elicited MEPs in left biceps brachii across a range of TMS intensities chosen to examine PN-mediated FAC and INH. Conditioning was applied using median nerve stimulation with an interstimulus interval that coincided with TMS and peripheral volleys summating at the C3-C4 level. All participants showed FAC at TMS intensities near active motor threshold and INH at slightly higher intensities. After tDCS, FAC was reduced for M1-M1 compared with Sham but not after PM-M1 stimulation. Contrary to an earlier study with cathodal tDCS, INH was unchanged across all sessions. The difference between these and earlier findings may relate to dual- vs. single-hemisphere M1 stimulation. M1-M1 tDCS may be a useful adjuvant to techniques that aim to reduce upper limb impairment after stroke.

The effect of intensive nutrition interventions on weight gain after kidney transplantation: protocol of a randomised controlled trial.

BACKGROUND: Weight gain and obesity are common after kidney transplantation, particularly during the first year. Obesity is a risk factor for the development of new-onset diabetes after transplantation, and is associated with reduced graft survival. There is a lack of evidence for effective interventions to prevent weight gain after kidney transplantation. METHODS/DESIGN: The effect of INTEnsive Nutrition interventions on weight gain after kidney Transplantation (INTENT) trial is a single-blind (outcomes assessor), randomised controlled trial to assess the effect of intensive nutrition interventions, including exercise advice, on weight gain and metabolic parameters in the first year after transplantation. Participants will be randomised during the first post-transplant month to either standard care (four visits with a renal dietitian over twelve months) or intensive nutrition intervention (eight visits with a renal dietitian over the first six months, four visits over the second six months, and three visits over the first six months with an exercise physiologist). In the intensive intervention group, nutrition counselling will be provided using motivational interviewing techniques to encourage quality engagement. Collaborative goal setting will be used to develop personalised nutrition care plans. Individualised advice regarding physical activity will be provided by an exercise physiologist. The primary outcome of the study is weight at six months after transplant, adjusted for baseline (one month post-transplant) weight, obesity and gender. Secondary outcomes will include changes in weight and other anthropometric measures over 12 months, body composition (in vivo neutron activation analysis, total body potassium, dual-energy X-ray absorptiometry, and bioelectrical impedance), biochemistry (fasting glucose, lipids, haemoglobin A1c and insulin), dietary intake and nutritional status, quality of life, and physical function. DISCUSSION: There are currently few randomised clinical trials of nutrition interventions after kidney transplantation. The INTENT trial will thus provide important data on the effect of intensive nutrition interventions on weight gain after transplant and the associated metabolic consequences. Additionally, by assessing changes in glucose metabolism, the study will also provide data on the feasibility of undertaking larger multi-centre trials of nutrition interventions to reduce the incidence or severity of diabetes after transplantation. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry Number: ACTRN12614000155695.

Primary motor and premotor cortex in implicit sequence learning--evidence for competition between implicit and explicit human motor memory systems.

Implicit and explicit memory systems for motor skills compete with each other during and after motor practice. Primary motor cortex (M1) is known to be engaged during implicit motor learning, while dorsal premotor cortex (PMd) is critical for explicit learning. To elucidate the neural substrates underlying the interaction between implicit and explicit memory systems, adults underwent a randomized crossover experiment of anodal transcranial direct current stimulation (AtDCS) applied over M1, PMd or sham stimulation during implicit motor sequence (serial reaction time task, SRTT) practice. We hypothesized that M1-AtDCS during practice will enhance online performance and offline learning of the implicit motor sequence. In contrast, we also hypothesized that PMd-AtDCS will attenuate performance and retention of the implicit motor sequence. Implicit sequence performance was assessed at baseline, at the end of acquisition (EoA), and 24 h after practice (retention test, RET). M1-AtDCS during practice significantly improved practice performance and supported offline stabilization compared with Sham tDCS. Performance change from EoA to RET revealed that PMd-AtDCS during practice attenuated offline stabilization compared with M1-AtDCS and sham stimulation. The results support the role of M1 in implementing online performance gains and offline stabilization for implicit motor sequence learning. In contrast, enhancing the activity within explicit motor memory network nodes such as the PMd during practice may be detrimental to offline stabilization of the learned implicit motor sequence. These results support the notion of competition between implicit and explicit motor memory systems and identify underlying neural substrates that are engaged in this competition.

Non-invasive brain stimulation enhances fine motor control of the hemiparetic ankle: implications for rehabilitation.

We set out to answer two questions with this study: 1. Can stroke patients improve voluntary control of their paretic ankle by practising a visuo-motor ankle-tracking task? 2. Are practice effects enhanced with non-invasive brain stimulation? A carefully selected sample of chronic stroke patients able to perform the experimental task attended three data collection sessions. Facilitatory transcranial direct current stimulation (tDCS) was applied in a random order over the lower limb primary motor cortex of the lesioned hemisphere or the non-lesioned hemisphere or sham stimulation was delivered over the lesioned hemisphere. In each session, tDCS was applied as patients practiced tracking a sinusoidal waveform for 15 min using dorsiflexion-plantarflexion movements of their paretic ankle. The difference in tracking error prior to, and after, the 15 min of practice was calculated. A practice effect was revealed following sham stimulation, and this effect was enhanced with tDCS applied over the lesioned hemisphere. The practice effect observed following sham stimulation was eliminated by tDCS applied over the non-lesioned hemisphere. The study provides the first evidence that non-invasive brain stimulation applied to the lesioned motor cortex of moderate- to well-recovered stroke patients enhances voluntary control of the paretic ankle. The results provide a basis for examining whether this enhanced ankle control can be induced in patients with greater impairments and whether enhanced control of a single or multiple lower limb joints improves hemiparetic gait patterns.

A paradox: after stroke, the non-lesioned lower limb motor cortex may be maladaptive.

What are the neuroplastic mechanisms that allow some stroke patients to regain high-quality control of their paretic leg, when others do not? One theory implicates ipsilateral corticospinal pathways projecting from the non-lesioned hemisphere. We devised a new transcranial magnetic stimulation protocol to identify ipsilateral corticospinal tract conductivity from the non-lesioned hemisphere to the paretic limb in chronic stroke patients. We also assessed corticospinal tract degeneration by diffusion tensor imaging, and used an ankle tracking task to assess lower limb motor control. We found greater tracking error during antiphase bilateral ankle movement for patients with strong conductivity from the non-lesioned hemisphere to the paretic ankle than for those with weak or no conductivity. These findings suggest that, instead of assisting motor control, contributions to lower limb motor control from the non-lesioned hemisphere of some stroke survivors may be maladaptive.

EMG breakthrough during cortical silent period in congenital hemiparesis: a descriptive case series.

BACKGROUND: The cortical silent period is a transient suppression of electromyographic activity after a transcranial magnetic stimulation pulse, attributed to spinal and supraspinal inhibitory mechanisms. Electromyographic breakthrough activity has been observed in healthy adults as a result of a spinal reflex response within the cortical silent period. OBJECTIVES: The objective of this case series is to report the ipsilesional and contralesional cortical silent period and the electromyographic breakthrough activity of 7 children with congenital hemiparesis. METHODS: TMS was delivered over the ipsilesional and contralesional primary motor cortices with resting motor threshold and cortical silent period measures recorded from first dorsal interosseous muscle. RESULTS: Seven children (13±2 years) were included. Ipsilesional and contralesional resting motor thresholds ranged from 49 to 80% and from 38 to 63% of maximum stimulator output, respectively. Ipsilesional (n=4) and contralesional (n=7) cortical silent period duration ranged from 49 to 206ms and 81 to 150ms, respectively. Electromyographic breakthrough activity was observed ipsilesionally in 3/4 (75%) and contralesionally in 3/7 (42.8%) participants. In the 3 children with ipsilesional breakthrough activity during the cortical silent period, all testing trials showed breakthrough. Contralesional breakthrough activity was observed in only one of the analyzable trials in each of those 3 participants. The mean peak amplitude of breakthrough activity ranged from 45 to 214µV (ipsilesional) and from 23 to 93µV (contralesional). CONCLUSION: Further research is warranted to understand the mechanisms and significance of electromyographic breakthrough activity within the cortical silent period in congenital hemiparesis. Understanding these mechanisms may lead to the design of tailored neuromodulation interventions for physical rehabilitation. TRIAL REGISTRATION: NCT02250092 (https://clinicaltrials.gov/ct2/show/NCT02250092).

Parent's Cardiorespiratory Fitness, Body Mass, and Chronic Disease Status Is Associated with Metabolic Syndrome in Young Adults: A Preliminary Study.

We sought to determine if there was an intergenerational association between parental weight, cardiorespiratory fitness (CRF), and disease status, with the prevalence of metabolic syndrome (MetSyn) in their young adult offspring. Young adults (n = 270, 21 ± 1 years, 53.3% female) were assessed for MetSyn and self-reported parent's CRF, body mass status, and disease status. MetSyn was present in 11.9% of participants, 27.4% had one or two components, and 58.5% had no components. A significantly higher percentage (93.9%) of young adults with MetSyn identified at least one parent as being overweight or obese, 84.8% reported low parental CRF and 87.9% reported a parent with disease (all p < 0.017). MetSyn in offspring is more likely when parents are perceived to have low CRF, increased body mass, and a diagnosis of disease. Evaluating the offspring of people with low CRF, elevated body mass, or who have a history of cardiovascular disease (CVD) or diabetes should be considered to promote early identification and treatment of young adults to reduce future premature CVD in these at-risk individuals.

Abnormal corticomotor excitability assessed in biceps brachii preceding pronator contraction post-stroke.

OBJECTIVE: To assess corticomotor (CM) excitability of the antagonist biceps brachii (BB) post-stroke in preparation for pronator contraction. In healthy subjects, we previously demonstrated that prior to pronator contraction CM excitability of the antagonist BB was suppressed. METHODS: Transcranial magnetic stimulation (TMS) was used to assess pre-contraction changes in motor evoked potential (MEP) amplitude of the BB, when BB was acting either as an antagonist or an agonist. TMS was applied 100-200ms prior to rhythmic isometric BB or pronator contractions in chronic stroke survivors and age/gender matched healthy control subjects. RESULTS: Prior to pronator contraction, MEPs in BB were elicited in the stroke group but were absent in healthy controls indicating that CM excitability of the antagonist BB was increased post-stroke. The extent of the abnormal increase in excitability positively correlated with the extent of upper limb motor impairment. CONCLUSIONS: Our results suggest that an alteration of cortical control mechanisms regulating motor excitability of the antagonist BB may contribute to the impairment of upper limb motor coordination post-stroke. SIGNIFICANCE: This study offers a unique approach to study the potential for a cortical origin of post-stroke motor discoordination.

Contralesional paired associative stimulation increases paretic lower limb motor excitability post-stroke.

Following stroke, an abnormally high interhemispheric inhibitory drive from the contralesional to the ipsilesional primary motor cortex (M1) is evident during voluntary movement. Down-regulating motor excitability of the contralesional M1 using inhibitory neuromodulatory protocols has demonstrated a correlation between balanced interhemispheric interactions and increased motor recovery. In 2005, our laboratory first reported bidirectional modulation of healthy subjects' tibialis anterior (TA) motor excitability during walking, using a stimulation paradigm known as paired associative stimulation (PAS). Suprathreshold transcranial magnetic stimulation (TMS) of the lower limb M1 paired with electrical stimulation of the common peroneal nerve produced a persistent modulation of TA corticomotor excitability. The present study tested the hypothesis that the excitability of the ipsilesional lower limb motor cortex during walking is increased when inhibitory PAS is applied to the contralesional motor cortex in chronic stroke survivors. We applied inhibitory PAS (120 pairs at 0.5 Hz) to the quiescent paretic TA of ten chronic stroke patients and the right TA of ten age-matched healthy subjects. Post intervention excitability measures were taken immediately following PAS, and again 5, 10 and 15 min later. When inhibitory PAS was applied to the non-paretic TA of chronic stroke subjects, the non-paretic TA motor evoked potential (MEP) amplitude decreased to 91% and paretic TA MEP amplitude increased to 130% (of pre-PAS values) during post-PAS walking. In healthy subjects, MEPs in response to TMS revealed that mean MEP amplitude from the stimulated TA decreased to 87% and the mean MEP amplitude from the non-stimulated TA increased to 126%. This is the first study to demonstrate that inhibitory PAS applied to the contralesional lower limb motor system of stroke survivors increases motor excitability of the paretic lower limb assessed during walking. This finding suggests that inhibitory PAS may be a useful tool to study how the human lower limb motor cortex recovers after neural injury, and that PAS may be a candidate adjuvant therapy for patients with neurological walking impairments.

Revisiting interhemispheric imbalance in chronic stroke: A tDCS study.

OBJECTIVE: Chronic stroke patients with moderate-severe motor impairment may have an increased reliance on contralesional vs ipsilesional motor areas to control the paretic arm. We hypothesised that increasing contralesional excitability with anodal transcranial direct current stimulation (a-tDCS) would benefit motor performance in patients with moderate-severe impairment. METHODS: Ten patients with motor impairment at the chronic stage after stroke received a-tDCS, cathodal (c-tDCS) and sham with the target electrode over contralesional motor cortex (M1). Motor performance was quantified from the circularity and size of planar movements made with the paretic arm. Contralateral and ipsilateral corticospinal excitability was inferred using transcranial magnetic stimulation. Corticospinal tract integrity and basal GABA concentration were assessed with magnetic resonance imaging and spectroscopy. RESULTS: Anodal tDCS increased contralesional corticomotor excitability evident from motor evoked potentials in both wrist extensors (both P<0.043). Cathodal tDCS did not affect corticomotor excitability (P>0.37). The effect of tDCS on motor performance with the paretic limb was negatively associated with ipsilesional GABA concentration after c-tDCS (P=0.001). CONCLUSIONS: Further investigation of noninvasive brain stimulation protocols that facilitate contralesional M1 is warranted. SIGNIFICANCE: The inter-hemispheric imbalance model of stroke recovery may not apply to patients with more severe impairment.

The use of transcranial magnetic stimulation to evaluate cortical excitability of lower limb musculature: Challenges and opportunities.

Neuroplasticity is a fundamental yet relatively unexplored process that can impact rehabilitation of lower extremity (LE) movements. Transcranial magnetic stimulation (TMS) has gained widespread application as a non-invasive brain stimulation technique for evaluating neuroplasticity of the corticospinal pathway. However, a majority of TMS studies have been performed on hand muscles, with a paucity of TMS investigations focused on LE muscles. This perspective review paper proposes that there are unique methodological challenges associated with using TMS to evaluate corticospinal excitability of lower limb muscles. The challenges include: (1) the deeper location of the LE motor homunculus; (2) difficulty with targeting individual LE muscles during TMS; and (3) differences in corticospinal circuity controlling upper and lower limb muscles. We encourage future investigations that modify traditional methodological approaches to help address these challenges. Systematic TMS investigations are needed to determine the extent of overlap in corticomotor maps for different LE muscles. A simple, yet informative methodological solution involves simultaneous recordings from multiple LE muscles, which will provide the added benefit of observing how other relevant muscles co-vary in their responses during targeted TMS assessment directed toward a specific muscle. Furthermore, conventionally used TMS methods (e.g., determination of hot spot location and motor threshold) may need to be modified for TMS studies involving LE muscles. Additional investigations are necessary to determine the influence of testing posture as well as activation state of adjacent and distant LE muscles on TMS-elicited responses. An understanding of these challenges and solutions specific to LE TMS will improve the ability of neurorehabilitation clinicians to interpret TMS literature, and forge novel future directions for neuroscience research focused on elucidating neuroplasticity processes underlying locomotion and gait training.

Spike-timing-dependent plasticity induced in resting lower limb cortex persists during subsequent walking.

Transcranial magnetic stimulation (TMS) of human lower limb motor cortex paired with common peroneal nerve electrical stimulation produces a lasting modulation of motor cortex excitability following the principles of spike-timing-dependent plasticity. We previously demonstrated that this "paired associative stimulation" (PAS) protocol applied during walking induced a bidirectional modulation of cortical excitability. The present study tested the hypothesis that the excitability of lower limb motor cortex assessed during walking is increased when PAS is applied to the resting cortex. PAS was delivered as a block of 120 pairs at 0.5 Hz to healthy subjects (n=13) in three separate sessions. TMS intensity was related to the active threshold obtained in tibialis anterior (TA) during the late swing phase of walking. Therefore, intensities used were below resting thresholds. When PAS using TMS intensities above active threshold was applied to the resting cortex, the normalized amplitude of potentials evoked in TA during subsequent walking increased to 124%. Using the same parameters and applying PAS during the late swing phase of walking, response amplitude increased to 114% of baseline. When the TMS intensity was set to active threshold, PAS applied to the resting cortex did not significantly modulate cortical excitability.

Suppression of motor evoked potentials in biceps brachii preceding pronator contraction.

Reciprocal control of antagonists is essential for coordinated limb movement. While Ia afferent dependent reciprocal inhibition has been extensively studied, reports of the control of antagonists during preparation for a motor action are limited. It has been demonstrated that corticomotor (CM) excitability of antagonists is suppressed prior to wrist extension/flexion suggesting the existence of a pre-contraction cortical control mechanism for distal upper limb antagonists. It is unknown whether pre-contraction suppression is evident in the control of proximal upper limb antagonists. Here we used transcranial magnetic stimulation and a rhythmic motor task to assess pre-contraction changes in excitability of corticospinal pathways projecting to biceps brachii (BB), when BB was an agonist (forearm supinator) or an antagonist. We found a suppression of motor evoked potential (MEP) amplitude in BB prior to pronator contraction and facilitation prior to BB contracting as a supinator. The extent of modulation was more profound as the agonist contraction approached. In contrast, there was no suppression evident in brachioradialis and triceps brachii under similar conditions indicating that pre-contraction suppression was specific to the antagonist BB. Our data in combination with published data from wrist muscles suggest that pre-contraction suppression of CM excitability may be a centrally induced mechanism to prevent antagonistic activity before Ia afferent dependent reciprocal inhibition is imposed. The importance of assessment of this inhibitory mechanism in neurologically impaired populations is discussed.

Propriospinal cutaneous-induced EMG suppression is unaltered by anodal tDCS of healthy motor cortex.

OBJECTIVE: Cervical propriospinal premotoneurons (PN) relay descending motor commands and integrate peripheral afferent feedback. Effects of anodal transcranial direct current stimulation (a-tDCS) on propriospinal excitability in the upper limbs are unknown. METHODS: Healthy right-handed adults received a-tDCS or sham tDCS over primary motor cortex (M1) at 1mA (Experiment 1, n=18) or 2mA current intensity (Experiment 2, n=15). Propriospinal excitability was assessed by suppression of background electromyography (EMG) in extensor carpi radialis (ECR) from electrical stimulation of the superficial radial nerve during bilateral (Experiment 1 and 2) or unilateral (Experiment 2 only) activation of the left and/or right ECR. EMG suppression could be attributed to an early propriospinal component and late cortical component. Motor evoked potentials (MEP) were obtained as a manipulation check. RESULTS: Before tDCS, propriospinal-mediated cutaneous-induced suppression was present in each arm for early and late components. ECR MEP amplitude increased after 1mA, but not 2mA, a-tDCS. Neither 1mA nor 2mA a-tDCS modulated either component of ipsilateral or contralateral propriospinal excitability during bilateral or unilateral tasks. CONCLUSIONS: Propriospinal-mediated cutaneous-induced suppression was not modulated by a-tDCS in healthy adults. SIGNIFICANCE: Reporting non-significant findings is paramount for the development of clinically-relevant tDCS protocols.

Effects of non-target leg activation, TMS coil orientation, and limb dominance on lower limb motor cortex excitability.

Transcranial magnetic stimulation (TMS) is used to examine corticospinal tract integrity after stroke, however, generating motor-evoked potentials (MEPs) in the lower limb (LL) can be difficult. Previous studies have used activation of the target leg to facilitate MEPs in the LL but this may not be possible after stroke due to hemiplegia. The dominance of the target limb may also be important, however the neurophysiological effects of LL dominance are not known. We investigated whether voluntary activation of the non-target leg combined with optimal TMS coil orientation increases corticomotor excitability in healthy adults, and whether limb dominance influences these results. TMS was delivered to induce a posterior-anterior (PA) and a medial-lateral (ML) cortical current in 22 healthy adults. MEPs were recorded in tibialis anterior (TA) with the participant at rest and when activating the non-target leg. We found that non-target leg activation increased corticomotor excitability in the target leg (reduced rest motor threshold (RMT) and MEP latency, and increased recruitment curve slope). ML cortical current also reduced RMT and MEP latency. The degree of footedness correlated with the degree of RMT asymmetry, with a PA but not ML cortical current direction. In summary, cross-facilitation by activating the non-target leg in a task requiring postural stabilisation and inducing ML current increase corticomotor excitability regardless of limb dominance. This protocol may have practical application in testing CST integrity after stroke when paretic limb thresholds are high, by increasing the likelihood of eliciting a MEP.