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.

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.

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.

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.

Prevalence of metabolic syndrome and metabolic syndrome components in young adults: A pooled analysis.

Metabolic syndrome (MetSyn) represents a clustering of different metabolic abnormalities. MetSyn prevalence is present in approximately 25% of all adults with increased prevalence in advanced ages. The presence of one component of MetSyn increases the risk of developing MetSyn later in life and likely represents a high lifetime burden of cardiovascular disease risk. Therefore we pooled data from multiple studies to establish the prevalence of MetSyn and MetSyn component prevalence across a broad range of ethnicities. PubMed, SCOPUS and Medline databases were searched to find papers presenting MetSyn and MetSyn component data for 18-30 year olds who were apparently healthy, free of disease, and MetSyn was assessed using either the harmonized, National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATPIII), American Heart Association/National Heart, Blood and Lung Institute (AHA/NHBLI), or International Diabetes Federation (IDF) definitions of MetSyn. After reviewing returned articles, 26,609 participants' data from 34 studies were included in the analysis and the data were pooled. MetSyn was present in 4.8-7% of young adults. Atherogenic dyslipidaemia defined as low high density lipoprotein (HDL) cholesterol was the most prevalent MetSyn component (26.9-41.2%), followed by elevated blood pressure (16.6-26.6%), abdominal obesity (6.8-23.6%), atherogenic dyslipidaemia defined as raised triglycerides (8.6-15.6%), and raised fasting glucose (2.8-15.4%). These findings highlight that MetSyn is prevalent in young adults. Establishing the reason why low HDL is the most prevalent component may represent an important step in promoting primary prevention of MetSyn and reducing the incidence of subsequent clinical disease.

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.

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.

Can motor imagery and hypnotic susceptibility explain Conversion Disorder with motor symptoms?

Marked distortions in sense of agency can be induced by hypnosis in susceptible individuals, including alterations in subjective awareness of movement initiation and control. These distortions, with associated disability, are similar to those experienced with Conversion Disorder (CD), an observation that has led to the hypothesis that hypnosis and CD share causal mechanisms. The purpose of this review is to explore the relationships among motor imagery (MI), hypnotic susceptibility, and CD, then to propose how MI ability may contribute to hypnotic responding and CD. Studies employing subjective assessments of mental imagery have found little association between imagery abilities and hypnotic susceptibility. A positive association between imagery abilities and hypnotic susceptibility becomes apparent when objective measures of imagery ability are employed. A candidate mechanism to explain motor responses during hypnosis is kinaesthetic MI, which engages a strategy that involves proprioception or the "feel" of movement when no movement occurs. Motor suppression imagery (MSI), a strategy involving inhibition of movement, may provide an alternate objective measurable phenomenon that underlies both hypnotic susceptibility and CD. Evidence to date supports the idea that there may be a positive association between kinaesthetic MI ability and hypnotic susceptibility. Additional evidence supports a positive association between hypnotic susceptibility and CD. Disturbances in kinaesthetic MI performance in CD patients indicate that MI mechanisms may also underlie CD symptoms. Further investigation of the above relationships is warranted to explain these phenomena, and establish theoretical explanations underlying sense of agency.

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.

'I-wave' Recruitment Determines Response to tDCS in the Upper Limb, but Only So Far.

BACKGROUND: Anodal transcranial direct current stimulation (a-tDCS) can facilitate primary motor cortex (M1), but the modulation of motor evoked potentials (MEPs) by a-tDCS varies between participants, and may depend on the balance between early versus late I-wave recruitment, as assessed by the difference in MEP latency between latero-medial and anterior-posterior cortical currents induced by transcranial magnetic stimulation (TMS). OBJECTIVE: To date, the dependence of tDCS after-effects on I-wave recruitment has only been investigated in intrinsic hand muscles. In order to better understand the effects of tDCS across the upper limb, the present study examined I-wave recruitment and MEP modulation by a-tDCS or dual-hemisphere tDCS in muscles of the forearm (Extensor Carpi Radialis; ECR) and proximal upper limb (Biceps Brachii; BB). METHODS: We conducted a randomized double-blind study with 18 healthy adults. Each received anodal, dual-hemisphere, or sham tDCS over M1 in separate sessions (tDCS, 1 mA for 15 min). RESULTS: Linear regression analyzes showed a-tDCS modulated MEP size dependent on the latency difference in the ECR (P = 0.01) but not BB (P = 0.28). Individuals with small MEP latency differences showed the expected facilitation of ECR MEPs after a-tDCS, whereas those with large MEP latency differences had suppressed ECR MEPs after a-tDCS. This relationship was not present after dual-hemisphere or sham tDCS in either muscle (all P > 0.32). CONCLUSIONS: I-wave recruitment can predict the after-effects of a-tDCS in the distal but not proximal upper limb. These findings provide further insight into the variability of tDCS after-effects, and the relationship between I-wave recruitment and putative mechanisms of tDCS.

Stance limb ground reaction forces in high functioning stroke and healthy subjects during gait initiation.

BACKGROUND: Following stroke, little is known about ground reaction forces during gait initiation. OBJECTIVE: To compare stroke patients' with healthy subjects' anterior, medial, and lateral ground reaction forces generated during gait initiation. METHODS: Patients with left paresis, right paresis, and age-similar healthy subjects were recruited. During gait initiation the average peak anterior, medial, and lateral ground reaction forces acting on each lower limb were calculated when it was the stance limb. FINDINGS: Anterior ground reaction forces acting on the right and left stance limbs of healthy subjects were greater than anterior forces acting on the nonparetic and paretic limbs of stroke patients. Medial ground reaction forces for the nonparetic and paretic limbs of stroke patients and for the right and left stance limbs of healthy subjects were equivalent. While lateral ground reaction forces acting on the nonparetic and paretic limbs were equivalent for left paretic patients, for right paretic patients lateral forces acting on the nonparetic limb were greater compared to the paretic limb and also greater compared to the left limb of healthy subjects. INTERPRETATION: An effect of side-of-lesion was revealed in average peak lateral ground reaction force data. Larger lateral ground reaction forces acting on the left nonparetic stance limb of right paretic patients compared to the right nonparetic stance limb of left paretic patients during gait initiation may be an indication of differing adaptations that depend on the side-of-lesion.

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.

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.

Corticomotor excitability of arm muscles modulates according to static position and orientation of the upper limb.

OBJECTIVE: We investigated how multi-joint changes in static upper limb posture impact the corticomotor excitability of the posterior deltoid (PD) and biceps brachii (BIC), and evaluated whether postural variations in excitability related directly to changes in target muscle length. METHODS: The amplitude of individual motor evoked potentials (MEPs) was evaluated in each of thirteen different static postures. Four functional postures were investigated that varied in shoulder and elbow angle, while the forearm was positioned in each of three orientations. Posture-related changes in muscle lengths were assessed using a biomechanical arm model. Additionally, M-waves were evoked in the BIC in each of three forearm orientations to assess the impact of posture on recorded signal characteristics. RESULTS: BIC-MEP amplitudes were altered by shoulder and elbow posture, and demonstrated robust changes according to forearm orientation. Observed changes in BIC-MEP amplitudes exceeded those of the M-waves. PD-MEP amplitudes changed predominantly with shoulder posture, but were not completely independent of influence from forearm orientation. CONCLUSIONS: Results provide evidence that overall corticomotor excitability can be modulated according to multi-joint upper limb posture. SIGNIFICANCE: The ability to alter motor pathway excitability using static limb posture suggests the importance of posture selection during rehabilitation aimed at retraining individual muscle recruitment and/or overall coordination patterns.

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.

Rewiring the brain: potential role of the premotor cortex in motor control, learning, and recovery of function following brain injury.

The brain is a plastic organ with a capability to reorganize in response to behavior and/or injury. Following injury to the motor cortex or emergent corticospinal pathways, recovery of function depends on the capacity of surviving anatomical resources to recover and repair in response to task-specific training. One such area implicated in poststroke reorganization to promote recovery of upper extremity recovery is the premotor cortex (PMC). This study reviews the role of distinct subdivisions of PMC: dorsal (PMd) and ventral (PMv) premotor cortices as critical anatomical and physiological nodes within the neural networks for the control and learning of goal-oriented reach and grasp actions in healthy individuals and individuals with stroke. Based on evidence emerging from studies of intrinsic and extrinsic connectivity, transcranial magnetic stimulation, functional neuroimaging, and experimental studies in animals and humans, the authors propose 2 distinct patterns of reorganization that differentially engage ipsilesional and contralesional PMC. Research directions that may offer further insights into the role of PMC in motor control, learning, and poststroke recovery are also proposed. This research may facilitate neuroplasticity for maximal recovery of function following brain injury.