Paired corticomotoneuronal stimulation of the preactivated ankle dorsiflexor: an open-label study of magnetic and electrical painless protocols.

Paired corticomotoneuronal stimulation (or electrical PCMS: ePCMS) is the repetitive pairing of an electrical stimulus to a nerve with a transcranial magnetic stimulation of the primary motor cortex (TMS-of-M1) to noninvasively influence spinal plasticity. We compared ePCMS with the new painless PCMS protocol pairing a magnetic stimulus to the nerve with TMS-of-M1 (mPCMS) in the preactivated tibial anterior muscle (TA). Sixteen healthy adults participated in two sessions (mPCMS, ePCMS), each with 180 pairs of [low-intensity TMS-of-M1 + nerve stimulation] at 0.2 Hz. TA motor-evoked potentials (MEP) to single-pulse TMS at pre-PCMS, immediately and 30 min after PCMS, were cluster-analyzed to discriminate responders and non-responders. Paired-pulse TMS-of-M1 and F-waves were also tested and BDNF polymorphism influence was explored. Both PCMS protocols significantly increased MEP amplitudes (n = 9 responders each), but the time-course differed with mPCMS inducing larger MEP increase over time. The number of BDNF-methionine carriers tended to be larger than Val66Val in mPCMS and the reverse in ePCMS, thus warranting further investigations. The MEP changes of the preactivated TA likely occurred at the pre-motoneuronal level and larger mPCMS after-effects over time may be related to the afferents recruited. mPCMS seems relevant to be tested in future studies as a painless noninvasive approach to induce sustained pre-motoneuronal plasticity in spinal cord injury.

Repetitive peripheral magnetic stimulation to improve ankle function and gait in cerebral palsy at adulthood: An open-label case study.

Repetitive peripheral magnetic stimulation (rPMS) is noninvasive and painless. It drives plasticity of the primary motor cortex (M1) in children with cerebral palsy (CP) and this improves the ankle function and gait. Our study explored whether rPMS of muscles could influence motricity in an adult CP case. A 30-year-old woman with mixed CP participated in four sessions (S1 to S4, one per week) where rPMS was applied bilaterally on leg and trunk muscles (tibialis anterior-TA, hamstrings, transverse abdominis, paraspinal multifidus). Clinical scores and M1 excitability (probed by transcranial magnetic stimulation) were tested at pre-rPMS at S1 (baseline) and S4, then 40 days later (follow-up). The active ankle dorsiflexion was significantly increased and the plantar flexors resistance to stretch reduced as compared to baseline. The improvement of the ankle function was carried-over to the quality of locomotor patterns. Changes persisted until follow-up and were paralleled by drastic changes of M1 excitability. These original findings of rPMS influence on M1 plasticity and motricity are promising for the functional improvement of adult people living with CP and should be replicated in larger-sampled studies.

Noninvasive stimulation of the unlesioned hemisphere and phonological treatment in a case of chronic anomia post-stroke.

Chronic lexical anomia after left hemisphere (LH) stroke improves under personalized phonological treatment (PT). Cortical linking between language and hand motor areas (hand_M1) questioned whether PT-related improvement relies on the unlesioned hemisphere (UH) plasticity when LH is dysfunctional. Our 70-yo-woman case study showed that 10 sessions of excitatory stimulation of UH_hand-M1 combined with PT hastened oral picture naming improvement as compared to sham+PT and changes were maintained together with changes of untrained items andcorticomotor excitability increase. This supports a role of stimulation-induced plasticity of UH_hand M1 in language recovery, at least in the improvement of lexical anomia in chronic stroke.

Checklist on the Quality of the Repetitive Peripheral Magnetic Stimulation (rPMS) Methods in Research: An International Delphi Study.

An increasing number of clinical research studies have used repetitive peripheral magnetic stimulation (rPMS) in recent years to alleviate pain or improve motor function. rPMS is non-invasive, painless, and administrated over peripheral nerve, spinal cord roots, or a muscle using a coil affixed to the skin and connected to a rapid-rate magnetic stimulator. Despite the clinical impact and scientific interest, the methodological inconsistencies or incomplete details and findings between studies could make the rPMS demonstration difficult to replicate. Given the lack of guidelines in rPMS literature, the present study aimed at developing a checklist to improve the quality of rPMS methods in research. An international panel of experts identified among those who had previously published on the topic were enrolled in a two-round web-based Delphi study with the aim of reaching a consensus on the items that should be reported or controlled in any rPMS study. The consensual rPMS checklist obtained comprises 8 subject-related items (e.g., age, sex), 16 methodological items (e.g., coil type, pulse duration), and 11 stimulation protocol items (e.g., paradigm of stimulation, number of pulses). This checklist will contribute to new interventional or exploratory rPMS research to guide researchers or clinicians on the methods to use to test and publish rPMS after-effects. Overall, the checklist will guide the peer-review process on the quality of rPMS methods reported in a publication. Given the dynamic nature of a consensus between international experts, it is expected that future research will affine the checklist.

Theta-Burst Stimulation of Forearm Muscles in Patients With Complex Regional Pain Syndrome: Influence on Brain and Clinical Outcomes.

Objective: Complex regional pain syndrome (CRPS) is a common pain condition characterized by the changes in the brain that are not yet addressed by conventional treatment regimens. Repetitive peripheral magnetic stimulation (rPMS) of muscles is painless and non-invasive and can influence these changes (the induction of brain plasticity) to reduce pain and improve motricity. In patients with CRPS, this open-label pilot study tested rPMS after-effects on the pain intensity and sensorimotor control of the upper limb along with the excitability changes of the primary motor cortex (M1). Methods: Eight patients with CRPS were enrolled in a single-session program. Patients were tested at pre- and post-rPMS over the flexor digitorum superficialis (FDS) muscle. The clinical outcomes were pain intensity, proprioception, active range of motion (ROM), and grip strength. M1 excitability was tested using the single- and paired-pulse transcranial magnetic stimulation (TMS) of M1. Results: In our small sample study, rPMS reduced instant and week pain, improved proprioception and ROM, and reduced the hemispheric imbalance of several TMS outcomes. The more M1 contralateral to the CRPS side was hyperactivated at baseline, the more pain was reduced. Discussion: This open-label pilot study provided promising findings for the use of rPMS in CRPS with a focus on M1 plastic changes. Future randomized, placebo-controlled clinical trials should confirm the existence of a causal relationship between the TMS outcomes and post-rPMS decrease of pain. This will favor the development of personalized treatments of peripheral non-invasive neurostimulation in CRPS.

Complex Regional Pain Syndrome. A Comprehensive Review on Neuroplastic Changes Supporting the Use of Non-invasive Neurostimulation in Clinical Settings.

Background: Complex regional pain syndrome (CRPS) is a rare debilitating disorder characterized by severe pain affecting one or more limbs. CRPS presents a complex multifactorial physiopathology. The peripheral and sensorimotor abnormalities reflect maladaptive changes of the central nervous system. These changes of volume, connectivity, activation, metabolism, etc., could be the keys to understand chronicization, refractoriness to conventional treatment, and developing more efficient treatments. Objective: This review discusses the use of non-pharmacological, non-invasive neurostimulation techniques in CRPS, with regard to the CRPS physiopathology, brain changes underlying chronicization, conventional approaches to treat CRPS, current evidence, and mechanisms of action of peripheral and brain stimulation. Conclusion: Future work is warranted to foster the evidence of the efficacy of non-invasive neurostimulation in CRPS. It seems that the approach has to be individualized owing to the integrity of the brain and corticospinal function. Non-invasive neurostimulation of the brain or of nerve/muscles/spinal roots, alone or in combination with conventional therapy, represents a fertile ground to develop more efficient approaches for pain management in CRPS.

A new method to elicit and measure movement illusions in stroke by means of muscle tendon vibration: the Standardized Kinesthetic Illusion Procedure (SKIP).

Purpose: Muscle tendon vibration (MTV) strongly activates muscle spindles and can evoke kinaesthetic illusions. Although potentially relevant for sensorimotor rehabilitation in stroke, MTV is scarcely used in clinical practice, likely because of the absence of standardised procedures to elicit and characterise movement illusions. This work developed and validated a Standardised Kinaesthetic Illusion Procedure (SKIP) to favour the use of MTV-induced illusions in clinical settings.Materials and methods: SKIP scores were obtained in 15 individuals with chronic stroke and 18 age- and gender-matched healthy counterparts. A further 13 healthy subjects were tested to provide more data with the general population. MTV was applied over the Achilles tendon and SKIP scoring system characterised the clearness and direction of the illusions of ankle dorsiflexion movements.Results: All healthy and stroke participants perceived movement illusions. SKIP scores on the paretic side were significantly lower compared to the non paretic and healthy. Illusions were less clear and sometimes in unexpected directions with the impaired ankle, but still possible to elicit in the presence of sensorimotor deficits.Conclusions: SKIP represents an ancillary and potentially useful clinical method to elicit and characterise illusions of movements induced by MTV. SKIP could be relevant to further assess the processing of proprioceptive afferents in stroke and their potential impact on motor control and recovery. It may be used to guide therapy and improve sensorimotor recovery. Future work is needed to investigate the metrological properties of our method (reliability, responsiveness, etc.), and also the neurophysiological underpinnings of MTV-induced illusions.

Altered transcallosal inhibition evidenced by transcranial magnetic stimulation highlights neurophysiological consequences of premature birth in early adulthood.

BACKGROUND AND OBJECTIVE: A very preterm birth can induce deleterious neurophysiological consequences beyond childhood; alterations of the corpus callosum (CC) are reported in adolescents born very preterm along with cognitive impairments. The question remains whether neurophysiological alterations are still detectable in adulthood such as an alteration in CC inhibitory function. The aim of the present study was thus to examine transcallosal inhibition in young adults born very preterm compared to counterparts born at term. STUDY PARTICIPANTS & METHODS: Transcallosal inhibition was probed by measuring the ipsilateral silent period (iSP) using transcranial magnetic stimulation (TMS) in 13 young adults born at 33w of gestation or less (20 ±â€¯3. 2y) and 12 young adults born at term (22 ±â€¯1. 75y). Single high-intensity TMS were delivered to the primary motor cortex (M1) ipsilateral to the preactivated first dorsal interosseous (FDI) muscle. Occurrence, latency, and duration of iSP were measured in the FDI EMG activity, for both hemispheres alternatively (10-12 trials each) along with their resting motor threshold (RMT). RESULTS: In individuals born very preterm as compared to individuals born at term, ISP occurred less frequently (p < .0001), its latency was longer (p = .004), especially in the non-dominant hemisphere, its duration shorter (p < .0001), and RMT was higher in the non-dominant M1 than in the dominant. CONCLUSIONS: Impairment of transcallosal inhibition along with asymmetry of M1 excitability in young adults born very preterm as compared to those born at term underline that neurophysiological consequences of a preterm birth can still be detected in early adulthood.

"Discrete peaks" of excitability and map overlap reveal task-specific organization of primary motor cortex for control of human forearm muscles.

The primary motor cortex (M1) presents a somatotopic organization of body parts, but with overlap between muscle/movement representations. This distinct but overlapping M1 organization is believed to be important for individuated control and movement coordination, respectively. Discrete peaks of greater excitability observed within M1 might underpin organization of cortical motor control. This study aimed to examine interactions between M1 representations of synergist and antagonist forearm muscles, compare regions of greater excitability during different functional tasks, and compare characteristics of M1 representation recorded using surface and fine-wire (fw ) electrodes. Transcranial magnetic stimulation (TMS) was applied over M1 for mapping the representation of 4 forearm muscles (extensor carpi radialis brevis [ECRB], extensor digitorum communis, flexor carpi radialis, and flexor digitorum superficialis) during three tasks: rest, grip, and wrist extension in 14 participants. There are three main findings. First, discrete areas of peak excitability within the M1 representation of ECRBfw were identified during grip and wrist extension suggesting that different M1 areas are involved in different motor functions. Second, M1 representations of synergist muscles presented with greater overlap of M1 representations than muscles with mainly antagonist actions, which suggests a role in muscle coordination. Third, as larger normalized map volume and overlap were observed using surface than fine-wire electrodes, data suggest that cross-talk from adjacent muscles compromised interpretation of recordings made with surface electrodes in response to TMS. These results provide a novel understanding of the spatial organization of M1 with evidence of "functional somatotopy." This has important implications for cortical control of movement. Hum Brain Mapp 38:6118-6132, 2017. © 2017 Wiley Periodicals, Inc.

Reliability of lower limb transcranial magnetic stimulation outcomes in the ipsi- and contralesional hemispheres of adults with chronic stroke.

OBJECTIVE: To investigate the ability of transcranial magnetic stimulation (TMS) outcomes in the chronic stroke population to (i) track individual plastic changes and (ii) detect differences between individuals. To this end, intrarater "test-retest" reliability (relative and absolute) was tested for the ipsilesional and contralesional hemispheres. METHODS: Thirteen participants with a unilateral stroke (≥6months ago) and sensorimotor impairments were enrolled. Single and paired-pulse TMS outcomes were obtained from the primary motor cortex (M1) representation of the tibialis anterior muscle in both hemispheres and at two sessions separated by one week. The standard error of the measurement (SEMeas), minimal detectable change (MDC) and intraclass correlation coefficient (ICC) were studied. RESULTS: Active motor threshold and latency of motor evoked potentials provided the lowest SEMeas and highest ICCs for both ipsi- and contralesional hemispheres. However, MDC were generally large, thus questioning the use of TMS outcomes to track individual plastic changes of M1. CONCLUSIONS: Our study provided supporting evidence of good to excellent intrarater reliability for a few TMS outcomes and proposed recommendations on the interpretation and the use of that knowledge in future work. SIGNIFICANCE: Psychometric properties of TMS measures should be further addressed in order to better understand how to refine their use in clinical settings.

After-effects of peripheral neurostimulation on brain plasticity and ankle function in chronic stroke: The role of afferents recruited.

AIMS OF THE STUDY: This study tested the after-effects of neuromuscular electrical stimulation (NMES), repetitive peripheral magnetic stimulation (rPMS) and muscle tendon vibration (VIB) on brain plasticity and sensorimotor impairments in chronic stroke to investigate whether different results could depend on the nature of afferents recruited by each technique. MATERIALS AND METHODS: Fifteen people with chronic stroke participated in five sessions (one per week). Baseline measures were collected in session one, then, each participant received 4 randomly ordered interventions (NMES, rPMS, VIB and a 'control' intervention of exercises). Interventions were applied to the paretic ankle muscles and parameters of application were matched as closely as possible. Standardized clinical measures of the ankle function on the paretic side and transcranial magnetic stimulation (TMS) outcomes of both primary motor cortices (M1) were collected at pre- and post-application of each intervention. RESULTS: The ankle muscle strength was significantly improved by rPMS and VIB (P≤0.02). rPMS influenced M1 excitability (increase in the contralesional hemisphere, P=0.03) and inhibition (decrease in both hemispheres, P≤0.04). The group mean of a few clinical outcomes improved across sessions, i.e. independently of the order of interventions. Some TMS outcomes at baseline could predict the responsiveness to rPMS and VIB. CONCLUSION: This original study suggests that rPMS and VIB were efficient to drive M1 plasticity and sensorimotor improvements, likely via massive inflows of 'pure' proprioceptive information generated. Usefulness of some TMS outcomes to predict which intervention a patient could be more responsive to should be further tested in future studies.

Repetitive peripheral magnetic neurostimulation of multifidus muscles combined with motor training influences spine motor control and chronic low back pain.

OBJECTIVE: The study tested whether combining repetitive peripheral magnetic stimulation (RPMS) and motor training of the superficial multifidus muscle (MF) better improved the corticomotor control of spine than training alone in chronic low back pain (CLBP). METHODS: Twenty-one participants with CLBP were randomly allocated to [RPMS+training] and [Sham+training] groups for three sessions (S1-S3) over a week where MF was stimulated before training (volitional contraction). Training was also home-practiced twice a day. Changes were tested at S1 and S3 for anticipatory postural adjustments (APAs) of MF and semi-tendinosus (ST), MF EMG activation, cortical motor plasticity (transcranial magnetic stimulation) and pain/disability. RESULTS: The RPMS group showed immediate decrease of pain at S1, then improvement of MF activation, ST APA, M1 facilitation, and pain/disability at S3. Changes were larger when brain excitability was lower at baseline. Disability index remained improved one month later. CONCLUSIONS: Combining RPMS with training of MF in CLBP impacted motor planning, MF and lumbopelvic spine motor control and pain/disability one week after the onset of protocol. Brain plasticity might have favoured motor learning and improved daily lumbopelvic spine control without pain generation. SIGNIFICANCE: Clinically, RPMS impacted the function by improving the gains beyond those reached by training alone in CLBP.

Reliability and minimal detectable change of transcranial magnetic stimulation outcomes in healthy adults: A systematic review.

BACKGROUND: Transcranial magnetic stimulation (TMS) is used worldwide for noninvasively testing human motor systems but its psychometric properties remain unclear. OBJECTIVE/HYPOTHESIS: This work systematically reviewed studies on the reliability of TMS outcome measures of primary motor cortex (M1) excitability in healthy humans, with an emphasis on retrieving minimal detectable changes (MDC). METHODS: The literature search was performed in three databases (Pubmed, CINAHL, Embase) up to June 2016 and additional studies were identified through hand-searching. French and English-written studies had to report the reliability of at least one TMS outcome of M1 in healthy humans. Two independent raters assessed the eligibility of potential studies, and eligible articles were reviewed using a structured data extraction form and two critical appraisal scales. RESULTS: A total of 34 articles met the selection criteria, which tested the intra- and inter-rater reliability (relative and absolute subtypes) of several TMS outcomes. However, our critical appraisal of studies raised concerns on the applicability and generalization of results because of methodological and statistical pitfalls. Importantly, MDC were generally large and likely affected by various factors, especially time elapsed between sessions and number of stimuli delivered. CONCLUSIONS: This systematic review underlined that the evidence about the reliability of TMS outcomes is scarce and affected by several methodological and statistical problems. Data and knowledge of the review provided however relevant insights on the ability of TMS outcomes to track plastic changes within an individual or within a group, and recommendations were made to level up the quality of future work in the field.

The side of chronic low back pain matters: evidence from the primary motor cortex excitability and the postural adjustments of multifidi muscles.

Hemispheric lateralization of pain processing was reported with overactivation of the right frontal lobe. Specifically in chronic low back pain (CLBP), functional changes in the left primary motor cortex (M1) with impaired anticipatory postural activation (APA) of trunk muscles have been observed. Given the connections between frontal and M1 areas for motor planning, it is hypothesized that the pain side could differently influence M1 function and APA of paravertebral multifidus (MF) muscles. This study aimed at testing whether people with right- versus left-sided CLBP showed different M1 excitability and APA. Thirty-five individuals with lateralized CLBP (19 right-sided and 16 left-sided) and 13 pain-free subjects (normative values) were tested for the excitability of MF M1 area (active motor threshold-AMT) with transcranial magnetic stimulation and for the latency of MF APA during bilateral shoulder flexion and during unilateral hip extension in prone lying. In the right-sided CLBP group, the AMT of both M1 areas was lower than in the left-sided group and the pain-free subjects; the latency of MF APA was shorter in bilateral shoulder flexion and in the left hip extension tasks as compared to the left-sided group. In CLBP, an earlier MF APA was correlated with lower AMT in both tasks. People with right-sided CLBP presented with increased M1 excitability in both hemispheres and earlier MF APA. These results likely rely on cortical motor adaptation related to the tasks and axial muscles tested. Future studies should investigate whether CLBP side-related differences have a clinical impact, e.g. in diagnosis and intervention.

A Multi-facetted Visual Analytics Tool for Exploratory Analysis of Human Brain and Function Datasets.

Brain research typically requires large amounts of data from different sources, and often of different nature. The use of different software tools adapted to the nature of each data source can make research work cumbersome and time consuming. It follows that data is not often used to its fullest potential thus limiting exploratory analysis. This paper presents an ancillary software tool called BRAVIZ that integrates interactive visualization with real-time statistical analyses, facilitating access to multi-facetted neuroscience data and automating many cumbersome and error-prone tasks required to explore such data. Rather than relying on abstract numerical indicators, BRAVIZ emphasizes brain images as the main object of the analysis process of individuals or groups. BRAVIZ facilitates exploration of trends or relationships to gain an integrated view of the phenomena studied, thus motivating discovery of new hypotheses. A case study is presented that incorporates brain structure and function outcomes together with different types of clinical data.

Revisiting the Corticomotor Plasticity in Low Back Pain: Challenges and Perspectives.

Chronic low back pain (CLBP) is a recurrent debilitating condition that costs billions to society. Refractoriness to conventional treatment, lack of improvement, and associated movement disorders could be related to the extensive brain plasticity present in this condition, especially in the sensorimotor cortices. This narrative review on corticomotor plasticity in CLBP will try to delineate how interventions such as training and neuromodulation can improve the condition. The review recommends subgrouping classification in CLBP owing to brain plasticity markers with a view of better understanding and treating this complex condition.

Paired-Pulse TMS and Fine-Wire Recordings Reveal Short-Interval Intracortical Inhibition and Facilitation of Deep Multifidus Muscle Fascicles.

OBJECTIVE: Paired-pulse transcranial magnetic stimulation (ppTMS) is used to probe inhibitory and excitatory networks within the primary motor cortex (M1). These mechanisms are identified for limb muscles but it is unclear whether they share properties with trunk muscles. The aim was to determine whether it was possible to test the intracortical inhibition and facilitation of the deep multifidus muscle fascicles (DM) and at which inter-stimulus intervals (ISI). METHODS: In ten pain-free individuals, TMS was applied over M1 and motor evoked potentials (MEP) were recorded using fine-wire electrodes in DM. MEPs were conditioned with subthreshold stimuli at ISIs of 1 to 12 ms to test short-interval intracortical inhibition (SICI) and at 15 ms for long-interval intracortical facilitation. Short-interval facilitation (SICF) was tested using 1-ms ISI. RESULTS: SICI of DM was consistently obtained with ISI of 1-, 3-, 4- and 12-ms. Facilitation of DM MEP was only identified using SICF paradigm. CONCLUSIONS: A similar pattern of MEP modulation with ISI changes for deep trunk and limb muscles implies that M1 networks share some functional properties. SIGNIFICANCE: The ppTMS paradigm presents a potential to determine how M1 inhibitory and excitatory mechanisms participate in brain re-organization in back pain that affects control of trunk muscles.