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• Repeated spaced multi-coil TMS protocol impacts motor cortex plasticity. • Repeated spaced cortical paired associative stimulation (cPAS) caused a cumulative, dose-dependent effect on motor cortex excitability. • Repeated spaced cPAS may provide a more direct and effective method for modifying specific neural circuits. Repeated spaced sessions of repetitive transcranial magnetic stimulation (TMS) to the human primary motor cortex can lead to dose-dependent increases in motor cortical excitability. However, this has yet to be demonstrated in a defined cortical circuit. We aimed to examine the effects of repeated spaced cortical paired associative stimulation (cPAS) on excitability in the motor cortex. cPAS was delivered to the primary motor cortex (M1) and posterior parietal cortex (PPC) with two coils. In the multi-dose condition, three sessions of cPAS were delivered 50-min apart. The single-dose condition had one session of cPAS, followed by two sessions of a control cPAS protocol. Motor-evoked potentials were evaluated before and up to 40 min after each cPAS session as a measure of cortical excitability. Compared to a single dose of cPAS, motor cortical excitability significantly increased after multi-dose cPAS. Increasing the number of cPAS sessions resulted in a cumulative, dose-dependent effect on excitability in the motor cortex, with each successive cPAS session leading to notable increases in potentiation. Repeated spaced cPAS sessions summate to increase motor cortical excitability induced by single cPAS. Repeated spaced cPAS could potentially restore abilities lost due to disorders like stroke. [ABSTRACT FROM AUTHOR]

People experiencing kinesiophobia are more likely to develop persistent disabilities and chronic pain. However, the impact of kinesiophobia on the motor system remains poorly understood. We investigated whether kinesiophobia could modulate shoulder pain-induced changes in (1) kinematic parameters and muscle activation during functional movement and (2) corticospinal excitability. Thirty healthy, pain-free subjects took part in the study. Shoulder, elbow, and finger kinematics, as well as electromyographic activity of the upper trapezius and anterior deltoid muscles, were recorded while subjects performed a pointing task before and during pain induced by capsaicin at the shoulder. Anterior deltoid cortical changes in excitability were assessed through the slope of transcranial magnetic stimulation input-output curves obtained before and during pain. Results revealed that pain reduced shoulder electromyographic activity and had a variable effect on finger kinematics, with individuals with higher kinesiophobia showing greater reduction in finger target traveled distance. Kinesiophobia scores were also correlated with the changes in deltoid corticospinal excitability, suggesting that the latter can influence motor activity as soon as the motor signal emerges. Taken together, these results suggest that pain and kinesiophobia interact with motor control adaptation. [ABSTRACT FROM AUTHOR]

Human corticospinal excitability (CSE) modulates during movement, when muscles are active, but also at rest, when muscles are not active. These changes in resting motor system excitability can be transient or longer lasting. Evidence from transcranial magnetic stimulation (TMS) studies suggests even relatively short periods of motor learning on the order of minutes can have lasting effects on resting CSE. Whether individuals are able to return CSE to out-of-task resting levels during the intertrial intervals (ITI) of behavioral tasks that do not include an intended motor learning component is an important question. Here, in twenty-five healthy young adults, we used single-pulse TMS and electromyography (EMG) to measure motor evoked potentials (MEPs) during two different resting contexts: (1) prior to engaging in the response task during which participants were instructed only to rest (out-of-task), and (2) ITI of a choice-reaction time task (in-task). In both contexts, five TMS intensities were used to evaluate possible differences in recruitment of corticospinal (CS) output across a range of inputs. We hypothesized resting state CSE would be greater during ITI than out-of-task rest, reflected in larger MEP amplitudes. Contrary to our hypothesis, we observed no significant difference in MEP amplitudes between out-of-task rest and in-task ITI, and instead found evidence of equivalence, indicating that humans are able to return to a stable motor resting state within seconds after a response. These data support the interpretation that rest is a uniform motor state in the healthy nervous system. In the future, our data may be a useful reference for motor disorder populations with an impaired ability to return to rest. [ABSTRACT FROM AUTHOR]

Abstract Tactile Imagery (TI) remains a fairly understudied phenomenon despite growing attention to this topic in recent years. Here, we investigated the effects of TI on corticospinal excitability by measuring motor evoked potentials (MEPs) induced by single-pulse transcranial magnetic stimulation (TMS). The effects of TI were compared with those of tactile stimulation (TS) and kinesthetic motor imagery (kMI). Twenty-two participants performed three tasks in randomly assigned order: imagine finger tapping (kMI); experience vibratory sensations in the middle finger (TS); and mentally reproduce the sensation of vibration (TI). MEPs increased during both kMI and TI, with a stronger increase for kMI. No statistically significant change in MEP was observed during TS. The demonstrated differential effects of kMI, TI and TS on corticospinal excitability have practical implications for devising the imagery-based and TS-based brain–computer interfaces (BCIs), particularly the ones intended to improve neurorehabilitation by evoking plasticity changes in sensorimotor circuitry.

Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation tool with potential for managing neuromuscular fatigue, possibly due to alterations in corticospinal excitability. However, inconsistencies in intra- and inter- individual variability responsiveness to tDCS limit its clinical use. Emerging evidence suggests harnessing homeostatic metaplasticity induced via tDCS may reduce variability and boost its outcomes, yet little is known regarding its influence on neuromuscular fatigue in healthy adults. We explored whether cathodal tDCS (ctDCS) prior to exercise combined with anodal tDCS (atDCS) could augment corticospinal excitability and attenuate neuromuscular fatigue. 15 young healthy adults (6 males, 22 ± 4 years) participated in four pseudo-randomised neuromodulation sessions: sham stimulation prior and during exercise, sham stimulation prior and atDCS during exercise, ctDCS prior and atDCS during exercise, ctDCS prior and sham stimulation during exercise. The exercise constituted an intermittent maximal voluntary contraction (MVC) of the right first dorsal interosseous (FDI) for 10 min. Neuromuscular fatigue was quantified as an attenuation in MVC force, while motor evoked potential (MEP) amplitude provided an assessment of corticospinal excitability. MEP amplitude increased during the fatiguing exercise, whilst across time, force decreased. There were no differences in MEP amplitudes or force between neuromodulation sessions. These outcomes highlight the ambiguity of harnessing metaplasticity to ameliorate neuromuscular fatigue in young healthy individuals. [ABSTRACT FROM AUTHOR]

Prior studies suggest resistance exercise as a potential form of motor learning due to task-specific corticospinal responses observed in single sessions of motor skill and resistance training. While existing literature primarily focuses on upper limb muscles, revealing a task-dependent nature in eliciting corticospinal responses, our aim was to investigate such responses after a single session of lower limb motor skill and resistance training. Twelve participants engaged in a visuomotor force tracking task, self-paced knee extensions, and a control task. Corticospinal, spinal, and neuromuscular responses were measured using transcranial magnetic stimulation (TMS) and peripheral nerve stimulation (PNS). Assessments occurred at baseline, immediately post, and at 30-min intervals over two hours. Force steadiness significantly improved in the visuomotor task (P < 0.001). Significant fixed-effects emerged between conditions for corticospinal excitability, corticospinal inhibition, and spinal excitability (all P < 0.001). Lower limb motor skill training resulted in a greater corticospinal excitability compared to resistance training (mean difference [MD] = 35%, P < 0.001) and control (MD; 37%, P < 0.001). Motor skill training resulted in a lower corticospinal inhibition compared to control (MD; – 10%, P < 0.001) and resistance training (MD; – 9%, P < 0.001). Spinal excitability was lower following motor skill training compared to control (MD; – 28%, P < 0.001). No significant fixed effect of Time or Time*Condition interactions were observed. Our findings highlight task-dependent corticospinal responses in lower limb motor skill training, offering insights for neurorehabilitation program design. [ABSTRACT FROM AUTHOR]

Transcranial magnetic stimulation (TMS) measures the excitability and inhibition of corticomotor networks. Despite its task-specificity, few studies have used TMS during dynamic movements and the reliability of TMS paired pulses has not been assessed during cycling. This study aimed to evaluate the reliability of motor evoked potentials (MEP) and short- and long-interval intracortical inhibition (SICI and LICI) on vastus lateralis and rectus femoris muscle activity during a fatiguing single-leg cycling task. Nine healthy adults (2 female) performed two identical sessions of counterweighted single-leg cycling at 60% peak power output until failure. Five single pulses and ten paired pulses were delivered to the motor cortex, and two maximal femoral nerve stimulations (Mmax) were administered during two baseline cycling bouts (unfatigued) and every 5 min throughout cycling (fatigued). When comparing both baseline bouts within the same session, MEP·Mmax−1 and LICI (both ICC: >0.9) were rated excellent while SICI was rated good (ICC: 0.7–0.9). At baseline, between sessions, in the vastus lateralis, Mmax (ICC: >0.9) and MEP·Mmax−1 (ICC: 0.7) demonstrated good reliability; LICI was moderate (ICC: 0.5), and SICI was poor (ICC: 0.3). Across the fatiguing task, Mmax demonstrated excellent reliability (ICC > 0.8), MEP·Mmax−1 ranged good to excellent (ICC: 0.7–0.9), LICI was moderate to excellent (ICC: 0.5–0.9), and SICI remained poorly reliable (ICC: 0.3–0.6). These results corroborate the cruciality of retaining mode-specific testing measurements and suggest that during cycling, Mmax, MEP·Mmax−1, and LICI measures are reliable whereas SICI, although less reliable across days, can be reliable within the same session. [ABSTRACT FROM AUTHOR]

After musculoskeletal injuries, there is often a loss of corticospinal control. Current tendon rehabilitation may not adequately address the corticospinal control of the muscle which may contribute to the recalcitrance of symptom recurrence. This review provides a summary of the current literature regarding the effectiveness of tempo-controlled resistance training (TCRT) in (1) promoting corticospinal plasticity, (2) improving physical performance, and (3) improving strength outcomes in healthy adults. A comprehensive literature search was conducted using electronic databases (PubMed, CINAHL, Embase, and Google Scholar) to identify relevant studies published between 2010 and 2023. Randomized control (RCT) studies that included recreationally trained and untrained healthy adults between 18 and 60 years of age and that compared a TCRT intervention to a control condition were included. Twelve of the 1255 studies identified in the initial search were included in the final analysis. Throughout all included studies, TCRT was shown to elicit greater neural adaptations compared to traditional resistance training methods (i.e., self-paced strength training). These results indicate that TCRT holds promise as an effective method for modulating corticospinal plasticity in healthy adults and may enhance neuromuscular adaptations, including improvements in CSE, decreased SICI, enhanced motor unit synchronization, and voluntary muscle activation. [ABSTRACT FROM AUTHOR]

Tactile Imagery (TI) remains a fairly understudied phenomenon despite growing attention to this topic in recent years. Here, we investigated the effects of TI on corticospinal excitability by measuring motor evoked potentials (MEPs) induced by single-pulse transcranial magnetic stimulation (TMS). The effects of TI were compared with those of tactile stimulation (TS) and kinesthetic motor imagery (kMI). Twenty-two participants performed three tasks in randomly assigned order: imagine finger tapping (kMI); experience vibratory sensations in the middle finger (TS); and mentally reproduce the sensation of vibration (TI). MEPs increased during both kMI and TI, with a stronger increase for kMI. No statistically significant change in MEP was observed during TS. The demonstrated differential effects of kMI, TI and TS on corticospinal excitability have practical implications for devising the imagery-based and TS-based brain–computer interfaces (BCIs), particularly the ones intended to improve neurorehabilitation by evoking plasticity changes in sensorimotor circuitry. [ABSTRACT FROM AUTHOR]

• Thirty-nine studies explored the effect of age on responsiveness to non-invasive brain stimulation neuroplasticity paradigms. • Pooled findings revealed age-dependent reduction in corticospinal excitability following certain neuroplasticity paradigms. • Considerable heterogeneity within some paradigms was evident, limiting interpretations of pooled analyses. We aimed to summarise and critically appraise the available evidence for the effect of age on responsiveness to non-invasive brain stimulation (NBS) paradigms delivered to the primary motor cortex. Four databases (Medline, Embase, PsycINFO and Scopus) were searched from inception to February 7, 2023. Studies investigating age group comparisons and associations between age and neuroplasticity induction from NBS paradigms were included. Only studies delivering neuroplasticity paradigms to the primary motor cortex and responses measured via motor-evoked potentials (MEPs) in healthy adults were considered. 39 studies, encompassing 40 experiments and eight NBS paradigms were included: paired associative stimulation (PAS; n = 12), repetitive transcranial magnetic stimulation (rTMS; n = 2), intermittent theta burst stimulation (iTBS; n = 8), continuous theta burst stimulation (cTBS; n = 7), transcranial direct and alternating current stimulation ((tDCS; n = 7; tACS; n = 2)), quadripulse stimulation (QPS; n = 1) and i-wave periodic transcranial magnetic stimulation (iTMS; n = 1). Pooled findings from PAS paradigms suggested older adults have reduced post-paradigm responses, although there was considerable heterogeneity. Mixed results were observed across all other NBS paradigms and post-paradigm timepoints. Whilst age-dependent reduction in corticospinal excitability is possible, there is extensive inter- and intra-individual variability both within and between studies, making it difficult to draw meaningful conclusions from pooled analyses. [ABSTRACT FROM AUTHOR]

State-dependent non-invasive brain stimulation (NIBS) informed by electroencephalography (EEG) has contributed to the understanding of NIBS inter-subject and inter-session variability. While these approaches focus on local EEG characteristics, it is acknowledged that the brain exhibits an intrinsic long-range dynamic organization in networks. This proof-of-concept study explores whether EEG connectivity of the primary motor cortex (M1) in the pre-stimulation period aligns with the Motor Network (MN) and how the MN state affects responses to the transcranial magnetic stimulation (TMS) of M1. One thousand suprathreshold TMS pulses were delivered to the left M1 in eight subjects at rest, with simultaneous EEG. Motor-evoked potentials (MEPs) were measured from the right hand. The source space functional connectivity of the left M1 to the whole brain was assessed using the imaginary part of the phase locking value at the frequency of the sensorimotor μ-rhythm in a 1 s window before the pulse. Group-level connectivity revealed functional links between the left M1, left supplementary motor area, and right M1. Also, pulses delivered at high MN connectivity states result in a greater MEP amplitude compared to low connectivity states. At the single-subject level, this relation is more highly expressed in subjects that feature an overall high cortico-spinal excitability. In conclusion, this study paves the way for MN connectivity-based NIBS. [ABSTRACT FROM AUTHOR]

Background: An essential factor in the validity of motor evoked potential (MEP)s recorded by transcranial magnetic stimulation (TMS) over multiple times is their test-retest reliability which to a large extent depends on the accuracy and competence of the assessor (intra-rater reliability). However, intra-rater reliability is infrequently reported in TMS studies suggesting that this is rarely done. Objectives: This study was conducted to determine the intra-rater within and between-session reliability of a newly trained TMS assessor prior to a main TMS study and report on the methodology used to encourage similar practice. Methods: Fourteen (10 males, 4 females; mean age: 32 ± 5.8 years) participants took part in the study. Motor evoked potentials were elicited from a relaxed, right first dorsal interosseous (FDI) muscle three times (T1, T2 and T3) across two testing sessions at least 48 hours apart. During the first session, MEPs were recorded twice (T1 and T2) within an interval of 20 minutes to determine the within (intra) session reliability of the assessor. During the second session, a single measurement was carried out (T3) which was compared to T1 to determine the inter-session reliability. Results: Repeated measure analysis of variance (ANOVA) did not reveal significant difference in the amplitude of the MEPs obtained across the three time periods (P = 0.196) demonstrating agreement in the MEPs and hence the reliability of the assessor. Additionally, the intraclass correlation coefficient (ICC) between T1 and T2; and T1 and T3 were 0.952 (P < 0.001) and 0.833 (P = 0.001) respectively further indicating the within and between sessions reliability of the assessor. Conclusions: The agreement between the three measured MEPs amplitude and the significant ICC demonstrates the reliability of the assessor in this study to use TMS for research. We suggest that the intra-rater reliability of new TMS operators should be established using the methodology in this report prior to main TMS studies. [ABSTRACT FROM AUTHOR]

Transcutaneous spinal cord stimulation (TSCS) has been shown to improve motor recovery in people with spinal cord injury (SCI). Some groups deliver TSCS modulated with a kHz‐frequency (TSCS–kHz); the intensity used for TSCS–kHz is usually set based on the motor threshold for TSCS, even though TSCS–kHz threshold is considerably higher than TSCS. As a result, TSCS–kHz interventions tend to be delivered at low intensities with respect to the motor threshold (~40%). In this study, we compared the effects of sub‐threshold TSCS and TSCS–kHz, when delivered at similar intensity relative to their own motor threshold. Experiment I compared the after‐effects of 20 min of sub‐threshold (40% threshold) TSCS and TSCS–kHz on spinal and corticospinal excitability in able‐bodied participants. Experiment II assessed the dose–response relationship of delivering short (10‐pulse) trains of TSCS and TSCS–kHz at three different current intensities relative to the threshold (40%, 60%, and 80%). Experiment I found that 20 min of TSCS–kHz at a 40% threshold decreased posterior root reflex amplitude (p < 0.05), whereas TSCS did not. In experiment II, motor‐evoked potential (MEP) amplitude increased following short trains of TSCS and TSCS–kHz of increasing intensity. MEP amplitude was significantly greater for TSCS–kHz compared with TSCS when delivered at 80% of the threshold (p < 0.05). These results suggest that TSCS and TSCS–kHz have different effects when delivered at similar intensity relative to their own threshold; both for immediate effects on corticospinal excitability and following prolonged stimulation on spinal excitability. These different effects may be utilized for optimal rehabilitation in people with SCI. [ABSTRACT FROM AUTHOR]

Contextual information may shape motor resonance and support intention understanding during observation of incomplete, ambiguous actions. It is unclear, however, whether this effect is contingent upon kinematics ambiguity or contextual information is continuously integrated with kinematics to predict the overarching action intention. Moreover, a differentiation between the motor mapping of the intention suggested by context or kinematics has not been clearly demonstrated. In a first action execution phase, 29 participants were asked to perform reaching-to-grasp movements towards big or small food objects with the intention to eat or to move; electromyography from the First Dorsal Interosseous (FDI) and Abductor Digiti Minimi (ADM) was recorded. Depending on object size, the intentions to eat or to move were differently implemented by a whole-hand or a precision grip kinematics, thus qualifying an action-muscle dissociation. Then, in a following action prediction task, the same participants were asked to observe an actor performing the same actions and to predict his/her intention while motor resonance was assessed for the same muscles. Of note, videos were interrupted at early or late action phases, and actions were embedded in contexts pointing toward an eating or a moving intention, congruently or incongruently with kinematics. We found greater involvement of the FDI or ADM in the execution of precision or whole-hand grips, respectively. Crucially, this pattern of activation was mirrored during observation of the same actions in congruent contexts, but it was cancelled out or reversed in the incongruent ones, either when videos were interrupted at either early or long phases of action deployment. Our results extend previous evidence by showing that contextual information shapes motor resonance not only under conditions of perceptual uncertainty but also when more informative kinematics is available.

Context: Arthrogenic muscle inhibition (AMI) continues to be a limiting factor in joint rehabilitation as the inability to volitionally activate muscle significantly dampens recovery. New evidence acquired at higher brain centers and in clinical populations continues to reshape our perspective of what AMI is and how to treat it. This review aims to stimulate discussion about the far-reaching effects of AMI by exploring the interconnected pathways by which it evolves. Objectives: To discuss how reflexive inhibition can lead to adaptations in brain activity, to illustrate how changes in descending motor pathways limit our ability to contract muscle following injury, and to summarize the emerging literature on the wide-reaching effects of AMI on other interconnected systems. Data Sources: The databases PubMed, SPORTDiscus, and Web of Science were searched for articles pertaining to AMI. Reference lists from appropriate articles were cross-referenced. Conclusion: AMI is a sequential and cumulative neurological process that leads to complex clinical impairments. Originating with altered afferent information arising from an injured joint, patients experience changes in afferent information, reflexive muscle inhibition, deficiencies in somatosensation, neuroplastic compensations in higher brain centers, and ultimately decreased motor output to the muscle surrounding the joint. Other aspects of clinical function, like muscle structure and psychological responses to injury, are also impaired and influenced by AMI. Removing, or reducing, AMI should continue to be a focus of rehabilitation programs to assist in the optimization of health after joint injury. [ABSTRACT FROM AUTHOR]

Local vibration (LV) applied over the muscle tendon constitutes a powerful stimulus to activate the muscle spindle primary (Ia) afferents that project to the spinal level and are conveyed to the cortical level. This study aimed to identify the neuromuscular changes induced by a 30-min LV-inducing illusions of hand extension on the vibrated flexor carpi radialis (FCR) and the antagonist extensor carpi radialis (ECR) muscles. We studied the change of the maximal voluntary isometric contraction (MVIC, experiment 1) for carpal flexion and extension, motor-evoked potentials (MEPs, experiment 2), cervicomedullary motor-evoked potentials (CMEPs, experiment 2), and Hoffmann's reflex (H-reflex, experiment 3) for both muscles at rest. Measurements were performed before (PRE) and at 0, 30, and 60 min after LV protocol. A lasting decrease in strength was only observed for the vibrated muscle. The reduction in CMEPs observed for both muscles seems to support a decrease in alpha motoneurons excitability. In contrast, a slight decrease in MEPs responses was observed only for the vibrated muscle. The MEP/CMEP ratio increase suggested greater cortical excitability after LV for both muscles. In addition, the H-reflex largely decreased for the vibrated and the antagonist muscles. The decrease in the H/CMEP ratio for the vibrated muscle supported both pre- and postsynaptic causes of the decrease in the H-reflex. Finally, LV-inducing illusions of movement reduced alpha motoneurons excitability for both muscles with a concomitant increase in cortical excitability. [ABSTRACT FROM AUTHOR]

Based on human motor cortex, the effective spatial resolution of transcranial magnetic stimulation (TMS) is often described as 5-20 mm, because small changes in TMS coil position can have large effects on motor-evoked potentials (MEPs). MEPs are often studied at rest, with muscles relaxed. During muscle contraction and movement, corticospinal excitability is higher, thresholds for effective stimulation are lower, and MEPs can be evoked from larger regions of scalp, so the effective spatial resolution of TMS is larger. We found that TMS over the supramarginal gyrus (SMG) impaired manual dexterity in the grooved pegboard task. It also resulted in short-latency MEPs in hand muscles, despite the coil being 55 mm away from the motor cortex hand area (M1). MEPs might be evoked by either a specific corticospinal connection from SMG or a remote but direct electromagnetic stimulation of M1. To distinguish these alternatives, we mapped MEPs across the scalp during rest, isotonic contraction, and manual dexterity tasks and ran electric field simulations to model the expected M1 activation from 27 scalp locations and four coil orientations. We also systematically reviewed studies using TMS during movement. Across five experiments, TMS over SMG reliably evoked MEPs during hand movement. These MEPs were consistent with direct M1 stimulation and substantially decreased corticospinal thresholds during natural movement. Systematic review suggested that 54 published experiments may have suffered from similar motor activation confounds. Our results have implications for the assumed spatial resolution of TMS, and especially when TMS is presented within 55 mm of the motor cortex. [ABSTRACT FROM AUTHOR]

In the absence of disease, humans produce smooth and accurate movement trajectories. Despite such 'macroscopic' aspect, the 'microscopic' structure of movements reveals recurrent (quasi‐rhythmic) discontinuities. To date, it is unclear how the sensorimotor system contributes to the macroscopic and microscopic architecture of movement. Here, we investigated how corticospinal excitability changes in relation to microscopic fluctuations that are naturally embedded within larger macroscopic variations in motor output. Participants performed a visuomotor tracking task. In addition to the 0.25 Hz modulation that is required for task fulfilment (macroscopic scale), the motor output shows tiny but systematic fluctuations at ∼2 and 8 Hz (microscopic scales). We show that motor‐evoked potentials (MEPs) elicited by transcranial magnetic stimulation (TMS) during task performance are consistently modulated at all (time) scales. Surprisingly, MEP modulation covers a similar range at both micro‐ and macroscopic scales, even though the motor output differs by several orders of magnitude. Thus, corticospinal excitability finely maps the multiscale temporal patterning of the motor output, but it does so according to a principle of scale invariance. These results suggest that corticospinal excitability indexes a relatively abstract level of movement encoding that may reflect the hierarchical organisation of sensorimotor processes. Key points: Motor behaviour is organised on multiple (time)scales.Small but systematic ('microscopic') fluctuations are engrained in larger and slower ('macroscopic') variations in motor output, which are instrumental in deploying the desired motor plan.Corticospinal excitability is modulated in relation to motor fluctuations on both macroscopic and microscopic (time)scales.Corticospinal excitability obeys a principle of scale invariance, that is, it is modulated similarly at all (time)scales, possibly reflecting hierarchical mechanisms that optimise motor encoding. [ABSTRACT FROM AUTHOR]

Both motor imagery and resistance–training enhance motor function and corticospinal excitability. We tested the hypothesis that young participants with significant resistance–training experience would show heightened corticospinal excitability during a single session of motor imagery training. Fifty-six participants (mean ± SD age = 22 ± 2 years) were divided into resistance–trained and untrained groups. Forty-one upper-body resistance trained (21 males, 20 females; mean ± SD relative one repetition maximum bench press = 0.922 ± 0.317 kg/kg) and 15 untrained (4 males, 11 females; mean ± SD relative one repetition maximum bench press = 0.566 ± 0.175 kg/kg) participants visited the laboratory on three separate occasions. The first visit served as the familiarization session. During visits 2 and 3, participants engaged in a hand/wrist motor imagery protocol or rested quietly (control condition) in a randomized order. Before and after the interventions, single-pulse transcranial magnetic stimulation (TMS) over the motor cortex was used to measure resting motor–evoked potential amplitude of the first dorsal interosseous muscle. Our main finding was that motor imagery acutely increased corticospinal excitability by ~64% (marginal means pre = 784.1 µV, post = 1246.6 µV; p < 0.001, d = 0.487). However, there was no evidence that the increase in corticospinal excitability was influenced by resistance–training experience. We suspect that our results may have been influenced by the specific nature of the motor imagery task. Our findings have important implications for motor imagery prescription and suggest that motor imagery training may be equally beneficial for both resistance–trained and untrained populations. This study was prospectively registered at ClinicalTrials.gov (Identifier: NCT03889548). [ABSTRACT FROM AUTHOR]

After musculoskeletal injuries, there is often a loss of corticospinal control. Current tendon rehabilitation may not adequately address the corticospinal control of the muscle which may contribute to the recalcitrance of symptom recurrence. This review provides a summary of the current literature regarding the effectiveness of tempo-controlled resistance training (TCRT) in (1) promoting corticospinal plasticity, (2) improving physical performance, and (3) improving strength outcomes in healthy adults. A comprehensive literature search was conducted using electronic databases (PubMed, CINAHL, Embase, and Google Scholar) to identify relevant studies published between 2010 and 2023. Randomized control (RCT) studies that included recreationally trained and untrained healthy adults between 18 and 60 years of age and that compared a TCRT intervention to a control condition were included. Twelve of the 1255 studies identified in the initial search were included in the final analysis. Throughout all included studies, TCRT was shown to elicit greater neural adaptations compared to traditional resistance training methods (i.e., self-paced strength training). These results indicate that TCRT holds promise as an effective method for modulating corticospinal plasticity in healthy adults and may enhance neuromuscular adaptations, including improvements in CSE, decreased SICI, enhanced motor unit synchronization, and voluntary muscle activation.

We tested previous post-hoc findings indicating a relationship between functional connectivity (FC) in the motor network and corticospinal excitability (CsE), in a real-time EEG-TMS experiment in healthy participants.We hypothesized that high FC between left and right motor cortex predicts high CsE.FC was quantified in real-time by single-trial phase-locking value (stPLV), and TMS single pulses were delivered based on the current FC. CsE was indexed by motor-evoked potential (MEP) amplitude in a hand muscle. Possible confounding factors (pre-stimulus μ-power and phase, interstimulus interval) were evaluated post hoc.MEPs were significantly larger during high FC compared to low FC. Post hoc analysis revealed that the FC condition showed a significant interaction with μ-power in the stimulated hemisphere. Further, inter-stimulus interval (ISI) interacted with high vs. low FC conditions. In summary, FC was confirmed to be predictive of CsE, but should not be considered in isolation from μ-power and ISI. Moreover, FC was complementary to μ-phase in predicting CsE. Motor network FC is another marker of real-time accessible CsE beyond previously established markers, in particular phase and power of the μ rhythm, and may help define a more robust composite biomarker of high/low excitability states of human motor cortex.

To enhance smooth muscle contraction and relaxation during rehabilitation and sports activities, a comprehensive understanding of the motor control mechanisms within the central nervous system is necessary. However, current knowledge on these aspects is insufficient. Therefore, this study aimed to deepen our understanding of motor controls, by investigating the alterations in corticospinal excitability within cortical motor areas related to muscle contraction and relaxation using motor imagery with a reaction time task paradigm. Transcranial magnetic stimulation was used to measure the motor‐evoked potentials in the first dorsal interosseous muscle of the right hand after the 'go' signal. Static weak muscle contraction (Experiment 1: 18 healthy participants) and resting state (Experiment 2: 16 healthy participants) were applied as background factors, and a trial without motor imagery was performed as a control. Muscle contraction was maintained in the background in the contraction motor imagery. A decrease in excitability in the relaxation motor imagery task occurred compared with the control. When the muscles were at rest, an increase in excitability in the contraction motor imagery and a transient increase in excitability in the relaxation motor imagery occurred compared with the control condition. Hence, the excitability of contraction and relaxation motor imagery is characterized by a continuous increase in excitability, transient increase and subsequent decrease in excitability, respectively. These results suggest that muscle contraction sensory information in the background condition may be necessary for muscle relaxation. Matching the background conditions may be crucial when utilizing motor imagery for rehabilitation or sports training. [ABSTRACT FROM AUTHOR]

Background: Major depressive disorder (MDD) is a prevalent mental health condition affecting millions worldwide, leading to disability and reduced quality of life. MDD poses a global health priority due to its early onset and association with other disabling conditions. Available treatments for MDD exhibit varying effectiveness, and a substantial portion of individuals remain resistant to treatment. Repetitive transcranial magnetic stimulation (rTMS), applied to the left and/or right dorsolateral prefrontal cortex (DLPFC), is an alternative treatment strategy for those experiencing treatment-resistant MDD. The objective of this study is to investigate whether this newer form of rTMS, namely theta burst stimulation (TBS), when performed unilaterally or bilaterally, is efficacious in treatment-resistant MDD. Methods: In this naturalistic, randomized double-blinded non-inferiority trial, participants with a major depressive episode will be randomized to receive either unilateral (i.e., continuous TBS [cTBS] to the right and sham TBS to the left DLPFC) or bilateral sequential TBS (i.e., cTBS to the right and intermittent TBS [iTBS] to the left DLPFC) delivered 5 days a week for 4–6 weeks. Responders will move onto a 6-month flexible maintenance phase where TBS treatment will be delivered at a decreasing frequency depending on degree of symptom mitigation. Several clinical assessments and neuroimaging and neurophysiological biomarkers will be collected to investigate treatment response and potential associated biomarkers. A non-inferiority analysis will investigate whether bilateral sequential TBS is non-inferior to unilateral TBS and regression analyses will investigate biomarkers of treatment response. We expect to recruit a maximal of 256 participants. This trial is approved by the Research Ethics Board of The Royal's Institute of Mental Health Research (REB# 2,019,071) and will follow the Declaration of Helsinki. Findings will be published in peer-reviewed journals. Discussion: Comprehensive assessment of symptoms and neurophysiological biomarkers will contribute to understanding the differential efficacy of the tested treatment protocols, identifying biomarkers for treatment response, and shedding light into underlying mechanisms of TBS. Our findings will inform future clinical trials and aid in personalizing treatment selection and scheduling for individuals with MDD. Trial registration: The trial is registered on https://clinicaltrials.gov/ct2/home (#NCT04142996). [ABSTRACT FROM AUTHOR]

Purpose: We tested if an acute ascending to 2320 m above sea level (asl) affects corticospinal excitability (CSE) and intracortical inhibition (SICI) measured with transcranial magnetic stimulation (TMS) at rest, before, during and after a traditional hypertrophy-oriented resistance training (RT) session. We also explored whether blood lactate concentration (BLa), ratings of perceived exertion (RPE), perceived muscular pain and total training volume differed when the RT session was performed at hypoxia (H) or normoxia (N). Methods: Twelve resistance-trained men performed eight sets of 10 repetitions at 70% of one repetition maximum of a bar biceps curl at N (SpO2 = 98.0 ± 0.9%) and H (at 2320 asl, SpO2 = 94.0 ± 1.9%) in random order. Before each session, a subjective well-being questionnaire, the resting motor threshold (rMT) and a single pulse recruitment curve were measured. Before, during and after the RT session, BLa, RPE, muscle pain, CSE and SICI were measured. Results: Before the RT session only the rMT differed between H (− 5.3%) and N (ES = 0.38). RPE, muscle pain and BLa increased through the RT session and were greater at H than N (12%, 54% and 15%, respectively) despite a similar training volume (1618 ± 468 kg vs. 1638 ± 509 kg). CSE was reduced during the RT session (~ 27%) but recovered ten minutes after, regardless of the environmental condition. SICI did not change after any RT session. Conclusions: The data suggest that acute exposure to moderate hypoxia slightly increased the excitability of the most excitable structures of the corticospinal tract but did not influence intracortical or corticospinal responses to a single RT session. [ABSTRACT FROM AUTHOR]

The link between emotional experience and motor body responses has long been acknowledged. A well-established approach to exploring the effect of the perception of emotional stimuli on the motor system is measuring variations in the excitability of the corticospinal tract (CSE) through motor-evoked potentials (MEP) elicited via transcranial magnetic stimulation (TMS). Previous evidence has indicated a selective increase in MEP amplitude while participants view emotional stimuli, such as emotional facial expressions, compared to neutral cues. However, it is still not clear whether this effect depends on the specific emotional meaning conveyed by the stimulus. In the present study, we explored whether viewing faces expressing the primary emotions compared to faces with a neutral expression affects individuals' CSE, measured using TMS-elicited MEPs. Specifically, we elicited MEPs from the left motor cortex (M1) while participants passively viewed the same faces expressing either anger, fear, disgust, happiness, sadness, surprise, and no emotion (in different blocks). We found that the observation of fearful, angry, disgusted, and happy facial expressions was associated with a significant increase in the MEPs' amplitude compared to neutral facial expressions, with a comparable enhancement in the CSE occurring across these emotions. In turn, viewing sad and surprised faces did not modulate the CSE. Overall, our findings suggest that only facial expressions that signal (real or potential) danger or a rewarding stimulus, but not emotional facial expressions per se, are capable of activating action-related mechanisms. [ABSTRACT FROM AUTHOR]

State-dependent non-invasive brain stimulation (NIBS) informed by electroencephalography (EEG) has contributed to the understanding of NIBS inter-subject and inter-session variability. While these approaches focus on local EEG characteristics, it is acknowledged that the brain exhibits an intrinsic long-range dynamic organization in networks. This proof-of-concept study explores whether EEG connectivity of the primary motor cortex (M1) in the pre-stimulation period aligns with the Motor Network (MN) and how the MN state affects responses to the transcranial magnetic stimulation (TMS) of M1. One thousand suprathreshold TMS pulses were delivered to the left M1 in eight subjects at rest, with simultaneous EEG. Motor-evoked potentials (MEPs) were measured from the right hand. The source space functional connectivity of the left M1 to the whole brain was assessed using the imaginary part of the phase locking value at the frequency of the sensorimotor μ-rhythm in a 1 s window before the pulse. Group-level connectivity revealed functional links between the left M1, left supplementary motor area, and right M1. Also, pulses delivered at high MN connectivity states result in a greater MEP amplitude compared to low connectivity states. At the single-subject level, this relation is more highly expressed in subjects that feature an overall high cortico-spinal excitability. In conclusion, this study paves the way for MN connectivity-based NIBS.

• Contralateral pain during submaximal contractions impaired exercise tolerance. • Neuromuscular function and corticospinal excitability were not altered by pain. • Pain may modulate exercise through pathways independent of corticomotor. Muscle pain is an important determinant of exercise tolerance, but its relationship with neurophysiological responses during a submaximal exercise trial is unclear. The purpose of this study was to determine the effect of persistent contralateral pain on neurophysiological function and perceptual responses during ipsilateral isometric knee extensions to task failure. Ten participants performed a single-leg repeated submaximal isometric knee extensions with (PAIN) or without (CTRL) constant pain induced by intermittent blood flow occlusion combined with evoked muscle contraction applied to the contralateral, resting leg. Transcranial magnetic stimulation (TMS) applied over the motor cortex was used to assess corticospinal excitability (quantified as motor evoked potentials), corticospinal inhibition (quantified as silent period duration), and short interval intracortical inhibition. Maximal voluntary contractions (MVCs), coupled with femoral nerve stimulation to the exercising leg, were performed every 12 submaximal contractions to assess neuromuscular function. Perceived leg pain and effort were also assessed throughout the exercise. The experimental pain shortened the time to task failure compared to CTRL (P = 0.019). Although time effects were present, no differences appeared between conditions for MVC force, voluntary activation, or potentiated twitch force across both tasks (all P > 0.05). Additionally, no differences between CTRL and PAIN were demonstrated for any TMS-derived measures assessing corticospinal responses. Exercising leg pain was higher in CTRL (P = 0.018), as was perceived exertion (P = 0.030). Overall, when using a persistent, submaximal experimental pain intervention, it appears that although muscle pain compromises exercise tolerance, this phenomenon occurs independently of potential alterations in corticomotor mechanisms. [ABSTRACT FROM AUTHOR]

Background: Interactions between the somatosensory and motor cortices are of fundamental importance for motor control. Although physically distant, face and hand representations are side by side in the sensorimotor cortex and interact functionally. Traumatic brachial plexus injury (TBPI) interferes with upper limb sensorimotor function, causes bilateral cortical reorganization, and is associated with chronic pain. Thus, TBPI may affect sensorimotor interactions between face and hand representations. Objective: The aim of this study was to investigate changes in hand-hand and face-hand sensorimotor integration in TBPI patients using an afferent inhibition (AI) paradigm. Method: The experimental design consisted of electrical stimulation (ES) applied to the hand or face followed by transcranial magnetic stimulation (TMS) to the primary motor cortex to activate a hand muscle representation. In the AI paradigm, the motor evoked potential (MEP) in a target muscle is significantly reduced when preceded by an ES at short-latency (SAI) or long-latency (LAI) interstimulus intervals. We tested 18 healthy adults (control group, CG), evaluated on the dominant upper limb, and nine TBPI patients, evaluated on the injured or the uninjured limb. A detailed clinical evaluation complemented the physiological investigation. Results: Although hand-hand SAI was present in both the CG and the TBPI groups, hand-hand LAI was present in the CG only. Moreover, less AI was observed in TBPI patients than the CG both for face-hand SAI and LAI. Conclusion: Our results indicate that sensorimotor integration involving both hand and face sensorimotor representations is affected by TBPI. [ABSTRACT FROM AUTHOR]

Transcranial direct current stimulation (tDCS) is a non‐invasive brain stimulation technique that can modulate brain activity through the application of low‐intensity electrical currents. Based on its reported effects on corticospinal excitability (CSE), tDCS has been used to study cognition in healthy individuals and reduce symptoms in a variety of clinical conditions. Despite its increasing popularity as a research and clinical tool, high interindividual variability has been reported in the response to protocols using transcranial magnetic stimulation (TMS) to assess tDCS‐induced changes in CSE leading to several nonsignificant findings. In this systematic review, studies that reported no significant modulation of CSE following tDCS were identified from PubMed and Embase (Ovid) databases. Forty‐three articles were identified where demographic, TMS and tDCS parameters were extracted. Overall, stimulation parameters, CSE measurements and participant characteristics were similar to those described in studies reporting positive results and were likewise heterogeneous between studies. Small sample sizes and inadequate blinding were notable features of the reviewed studies. This systematic review suggests that studies reporting nonsignificant findings do not markedly differ from those reporting significant modulation of CSE. [ABSTRACT FROM AUTHOR]

Purpose: The effectiveness of a neuromuscular electrical stimulation (NMES) program is proportional to the level of evoked torque, which can be achieved with either conventional or wide‐pulse stimulations. The aim of this study was to compare evoked torque, objective fatigability, and related peripheral and central alterations, as well as changes in central nervous system (CNS) excitability induced by an acute session of conventional versus wide‐pulse NMES. Methods: Seventeen young men underwent three 20‐min NMES sessions: conventional (0.2 ms/50 Hz), wide‐pulse at 50 Hz (1 ms/50 Hz), and wide‐pulse at 100 Hz (1 ms/100 Hz). Neuromuscular measurements (i.e., maximal voluntary contraction, voluntary activation, evoked responses to femoral nerve stimulation, and CNS excitability) were performed on the right quadriceps femoris muscle before and after each NMES session. CNS excitability was measured using transcranial magnetic, thoracic, and transcutaneous spinal cord stimulations. Results: The level of evoked torque was not significantly different between conventional and wide‐pulse protocols applied at the maximal tolerable current intensity. All NMES protocols induced objective fatigability (~14% decrease in maximal voluntary contraction torque, p < 0.001) associated with peripheral (decrease in doublet torque and potentiated M‐wave amplitude, p = 0.002 and p < 0.001, respectively) but not central (unchanged voluntary activation, p = 0.79) alterations. However, these acute changes did not differ between NMES protocols and none of the NMES protocols modified markers of CNS excitability. Conclusion: These results may allow to conjecture that chronic effects and treatment effectiveness could be comparable between conventional and wide‐pulse NMES. [ABSTRACT FROM AUTHOR]

Background: After spinal cord injury (SCI), the excitability of the primary motor cortex (M1) lower extremity area decreases or disappears. A recent study reported that the M1 hand area of the SCI patient encodes the activity information of both the upper and lower extremities. However, the characteristics of the M1 hand area corticospinal excitability (CSE) changes after SCI and its correlation with extremities motor function are still unknown. Methods: A retrospective study was conducted on the data of 347 SCI patients and 80 healthy controls on motor evoked potentials (MEP, reflection of CSE), extremity motor function, and activities of daily living (ADL) ability. Correlation analysis and multiple linear regression analysis were conducted to analyze the relationship between the degree of MEP hemispheric conversion and extremity motor function/ADL ability. Results: The CSE of the dominant hemisphere M1 hand area decreased in SCI patients. In 0--6 m, AIS A grade, or non-cervical injury SCI patients, the degree of M1 hand area MEP hemispheric conversion was positively correlated with total motor score, lower extremity motor score (LEMS), and ADL ability. Multiple linear regression analysis further confirmed the contribution of MEP hemispheric conversion degree in ADL changes as an independent factor. Conclusion: The closer the degree of M1 hand area MEP hemispheric conversion is to that of healthy controls, the better the extremity motor function/ADL ability patients achieve. Based on the law of this phenomenon, targeted intervention to regulate the excitability of bilateral M1 hand areas might be a novel strategy for SCI overall functional recovery. [ABSTRACT FROM AUTHOR]

Repetitive Transcranial Magnetic Stimulation (rTMS) and transspinal electrical stimulation (tsES) have been proposed as a novel neurostimulation modality for individuals with incomplete spinal cord injury (iSCI). In this study, we integrated magnetic and electrical stimulators to provide neuromodulation therapy to individuals with incomplete spinal cord injury (iSCI). We designed a clinical trial comprising an 8-week treatment period and a 4-week treatment-free observation period. Cortical excitability, clinical features, inertial measurement unit and surface electromyography were assessed every 4 weeks. Twelve individuals with iSCI were recruited and randomly divided into a combined therapy group, a magnetic stimulation group, an electrical stimulation group, or a sham stimulation group. The magnetic and electric stimulations provided in this study were intermittent theta-burst stimulation (iTBS) and 2.5-mA direct current (DC) stimulation, respectively. Combined therapy, which involves iTBS and transspinal DC stimulation (tsDCS), was more effective than was iTBS alone or tsDCS alone in terms of increasing corticospinal excitability. In conclusion, the effectiveness of 8-week combined therapy in increasing corticospinal excitability faded 4 weeks after the cessation of treatment. According to the results, combination of iTBS rTMS and tsDCS treatment was more effective than was iTBS rTMS alone or tsDCS alone in enhancing corticospinal excitability. Although promising, the results of this study must be validated by studies with longer interventions and larger sample sizes.

Abstract Background Idiopathic normal pressure hydrocephalus (iNPH) is a multifactorial disease presenting with a classical symptom triad of cognitive decline, gait disturbance and urinary incontinence. The symptoms can be alleviated with shunt surgery but the etiology of the symptoms remains unclear. Navigated transcranial magnetic stimulation (nTMS) was applied to characterize corticospinal excitability and cortical motor function before and after shunt surgery in order to elucidate the pathophysiology of iNPH. We also aimed to determine, whether nTMS could be applied as a predictive tool in the pre-surgical work-up of iNPH. Methods 24 patients with possible or probable iNPH were evaluated at baseline, after cerebrospinal fluid drainage test (TAP test) and three months after shunt surgery (follow-up). Symptom severity was evaluated on an iNPH scale and with clinical tests (walking test, Box & Block test, grooved pegboard). In the nTMS experiments, resting motor threshold (RMT), silent period (SP), input–output curve (IO-curve), repetition suppression (RS) and mapping of cortical representation areas of hand and foot muscles were assessed. Results After shunt surgery, all patients showed improved performance in gait and upper limb function. The nTMS parameters showed an increase in the RMTs (hand and foot) and the maximum value of the IO-curve increased in subject with a good surgical outcome. The improvement in gait correlated with an increase in the maximum value of the IO-curve. SP, RS and mapping remained unchanged. Conclusion The excitability of the motor cortex and the corticospinal tract increased in iNPH patients after shunt surgery. A favorable clinical outcome of shunt surgery is associated with a higher ability to re-form and maintain neuronal connectivity.

Featured Application: PAS and MI are easy-to-implement rehabilitation interventions whose potential appears to be confirmed for hand motor recovery after stroke. However, there does not seem to be a specific advantage in combining PAS and MI interventions, as designed in MIPAS. Paired associative stimulation (PAS) is an intervention that modulates cortical plasticity. Motor imagery (MI) is used in the rehabilitation of stroke patients. We aimed to evaluate the possible synergistic effect of associating both interventions for potentiating motor recovery poststroke. MIPAS is a single-center, randomized controlled trial that enrolled 24 hemiparetic poststroke participants. Three single-session interventions were tested in a crossover design: PAS/MI, PAS, and ShamPAS/MI during which the affected Extensor Carpi Radialis (ECR) muscle was targeted. During MI, the participants were instructed to imagine extending their paretic wrist. We used Sham, subthreshold stimulation during ShamPAS. Changes in ECR Motor-Evoked Potential (MEP) areas and paretic wrist Range of Motion (aROM) during active extension were compared between the interventions. We observed no significant superior effect of any intervention, neither on MEP nor on wrist aROM. A time of assessment effect was highlighted for both outcome measures, with MEP- and aROM-measured post-interventions significantly higher than those measured pre-intervention. Despite the beneficial effect of each intervention on participant paretic wrist motor function, not always associated with MEP change, our results do not highlight a specific advantage in combining PAS and MI interventions in post-stroke motor rehabilitation. [ABSTRACT FROM AUTHOR]

Physical activity (PA) has been shown to benefit various cognitive functions and promote neuroplasticity. Whereas the effects of PA on brain anatomy and function have been well documented in older individuals, data are scarce in young adults. Whether high levels of cardiorespiratory fitness (CRF) achieved through regular PA are associated with significant structural and functional changes in this age group remains largely unknown. In the present study, twenty young adults that engaged in at least 8 hours per week of aerobic exercise during the last 5 years were compared to twenty sedentary controls on measures of cortical excitability, white matter microstructure, cortical thickness and metabolite concentration. All measures were taken in the left primary motor cortex and CRF was assessed with VO 2max. Transcranial magnetic stimulation (TMS) revealed higher corticospinal excitability in high- compared to low-fit individuals reflected by greater input/output curve amplitude and slope. No group differences were found for other TMS (short-interval intracortical inhibition and intracortical facilitation), diffusion MRI (fractional anisotropy and apparent fiber density), structural MRI (cortical thickness) and magnetic resonance spectroscopy (NAA, GABA, Glx) measures. Taken together, the present data suggest that brain changes associated with increased CRF are relatively limited, at least in primary motor cortex, in contrast to what has been observed in older adults. [ABSTRACT FROM AUTHOR]

Current literature lacks consolidated evidence for the impact of stimulation parameters on the effects of transcranial direct current stimulation (tDCS) in enhancing upper limb motor learning. Hence, we aim to synthesise available methodologies and results to guide future research on the usage of tDCS on upper limb motor learning, specifically in older adults and Parkinson's disease (PD). Thirty-two studies (Healthy older adults, N = 526, M = 67.25, SD = 4.30 years; PD, N = 216, M = 66.62, SD = 6.25 years) were included in the meta-analysis. All included studies consisted of active and sham protocols. Random effect meta-analyses were conducted for (i) subjects (healthy older adults and PD); (ii) intensity (1.0, 1.5, 2 mA); (iii) electrode montage (unilateral anodal, bilateral anodal, unilateral cathodal); (iv) stimulation site (cerebellum, frontal, motor, premotor, SMA, somatosensory); (v) protocol (online, offline). Significant tDCS effect on motor learning was reported for both populations, intensity 1.0 and 2.0 mA, unilateral anodal and cathodal stimulation, stimulation site of the motor and premotor cortex, and both online and offline protocols. Regression showed no significant relationship between tDCS effects and density. The efficacy of tDCS is also not affected by the number of sessions. However, studies that reported only single session tDCS found significant negative association between duration with motor learning outcomes. Our findings suggest that different stimulation parameters enhanced upper limb motor learning in older adults and PD. Future research should combine tDCS with neuroimaging techniques to help with optimisation of the stimulation parameters, considering the type of task and population. [ABSTRACT FROM AUTHOR]

Motor skill training alters the human nervous system; however, lower limb motor tasks have been less researched compared to upper limb tasks. This meta-analysis with best evidence synthesis aimed to determine the cortical and subcortical responses that occur following lower limb motor skill training, and whether these responses are accompanied by improvements in motor performance. Following a literature search that adhered to the PRISMA guidelines, data were extracted and analysed from six studies (n = 172) for the meta-analysis, and 11 studies (n = 257) were assessed for the best evidence synthesis. Pooled data indicated that lower limb motor skill training increased motor performance, with a standardised mean difference (SMD) of 1.09 being observed. However, lower limb motor skill training had no effect on corticospinal excitability (CSE), Hoffmann's reflex (H-reflex) or muscle compound action potential (MMAX) amplitude. The best evidence synthesis found strong evidence for improved motor performance and reduced short-interval cortical inhibition (SICI) following lower limb motor skill training, with conflicting evidence towards the modulation of CSE. Taken together, this review highlights the need for further investigation on how motor skill training performed with the lower limb musculature can modulate corticospinal responses. This will also help us to better understand whether these neuronal measures are underpinning mechanisms that support an improvement in motor performance. [ABSTRACT FROM AUTHOR]

BackgroundInteractions between the somatosensory and motor cortices are of fundamental importance for motor control. Although physically distant, face and hand representations are side by side in the sensorimotor cortex and interact functionally. Traumatic brachial plexus injury (TBPI) interferes with upper limb sensorimotor function, causes bilateral cortical reorganization, and is associated with chronic pain. Thus, TBPI may affect sensorimotor interactions between face and hand representations.ObjectiveThe aim of this study was to investigate changes in hand–hand and face–hand sensorimotor integration in TBPI patients using an afferent inhibition (AI) paradigm.MethodThe experimental design consisted of electrical stimulation (ES) applied to the hand or face followed by transcranial magnetic stimulation (TMS) to the primary motor cortex to activate a hand muscle representation. In the AI paradigm, the motor evoked potential (MEP) in a target muscle is significantly reduced when preceded by an ES at short-latency (SAI) or long-latency (LAI) interstimulus intervals. We tested 18 healthy adults (control group, CG), evaluated on the dominant upper limb, and nine TBPI patients, evaluated on the injured or the uninjured limb. A detailed clinical evaluation complemented the physiological investigation.ResultsAlthough hand–hand SAI was present in both the CG and the TBPI groups, hand–hand LAI was present in the CG only. Moreover, less AI was observed in TBPI patients than the CG both for face–hand SAI and LAI.ConclusionOur results indicate that sensorimotor integration involving both hand and face sensorimotor representations is affected by TBPI.

Context: Assessment of physical function for individuals after anterior cruciate ligament reconstruction (ACL-R) is complex and warrants the use of diverse evaluation strategies. To maximize the efficiency of assessment, there is a need to identify tests that provide the most meaningful information about this population. Objective: To investigate underlying constructs of quadriceps muscle function that uniquely describe aspects of performance in patients after ACL-R and establish clinical thresholds for measures able to classify patients with and without ACL-R. Design: Cross-sectional. Setting: Research laboratory. Patients (or Other Participants): Seventy-two patients with a primary, unilateral ACL-R (32 males and 40 females, age = 26.0 [9.3] y, time since surgery = 46.5 [58.0] mo) and 30 healthy controls (12 males and 18 females, age = 22.7 [4.6] y). Intervention(s): Quadriceps function was assessed bilaterally during 1 study visit. Main Outcome Measures: Isokinetic strength (peak torque, total work, and average power) at 90° and 180°/s, maximal voluntary isometric contraction torque, fatigue index, central activation ratio, Hoffmann reflex, and active motor threshold. Principal component analyses were performed for the involved limb, contralateral limb, and limb symmetry. Receiver–operator characteristic curve analyses were conducted to determine the diagnostic utility of each variable. Binary logistic regression was used to predict group membership (ACL-R vs healthy). Results: Three components of peripheral, central, and combined (peripheral and central) muscle function were identified, explaining 70.7% to 80.5% of variance among measures of quadriceps function. Total knee-extensor work at 90°/s (≥18.4 J/kg), active motor threshold (≥39.5%), and central activation ratio (≥94.7%) of the involved limb were strong predictors of patient status and correctly classified 83.5% of patients with ACL-R (P <.001). Conclusions: Unique constructs of peripheral, central, and combined muscle function exist in patients with ACL-R. Total knee-extensor work at 90°/s, active motor threshold, and central activation ratio consistently explained a significant portion of variance in measures of quadriceps function, demonstrated acceptable to excellent diagnostic utility, and predicted group membership with 72.8% to 83.5% accuracy. [ABSTRACT FROM AUTHOR]

The central nervous system has a remarkable ability to plan motor actions, to predict and monitor the sensory consequences during and following motor actions and integrate these into future actions. Numerous studies investigating human motor learning have employed tasks involving either force control during isometric contractions or position control during dynamic tasks. To our knowledge, it remains to be elucidated how motor practice with an emphasis on position control influences force control and vice versa. Furthermore, it remains unexplored whether these distinct types of motor practice are accompanied by differential effects on corticospinal excitability. In this study, we tested motor accuracy and effects of motor practice in a force or position control task allowing wrist flexions of the non-dominant hand in the absence of online visual feedback. For each trial, motor performance was quantified as errors (pixels) between the displayed target and the movement endpoint. In the main experiment, 46 young adults were randomized into three groups: position control motor practice (PC), force control motor practice (FC), and a resting control group (CON). Following assessment of baseline motor performance in the position and force control tasks, intervention groups performed motor practice with, augmented visual feedback on performance. Motor performance in both tasks was assessed following motor practice. In a supplementary experiment, measures of corticospinal excitability were obtained in twenty additional participants by application of transcranial magnetic stimulation to the primary motor cortex hot spot of the flexor carpi radialis muscle before and following either position or force control motor practice. Following motor practice, accuracy in the position task improved significantly more for PC compared to FC and CON. For the force control task, both the PC and FC group improved more compared to CON. The two types of motor practice thus led to distinct effects including positive betweentask transfer accompanying dynamic motor practice The results of the supplementary study demonstrated an increase in corticospinal excitability following dynamic motor practice compared to isometric motor practice. In conclusion, dynamic motor practice improves movement accuracy, and force control and leads to increased corticospinal excitability compared to isometric motor practice. [ABSTRACT FROM AUTHOR]

Motor imagery (MI) refers to the mental simulation of an action without overt movement. While numerous transcranial magnetic stimulation (TMS) studies provided evidence for a modulation of corticospinal excitability and intracortical inhibition during MI, the neural signature within the primary motor cortex is not clearly established. In the current study, we used directional TMS to probe the modulation of the excitability of early and late indirect waves (I‐waves) generating pathways during MI. Corticospinal responses evoked by TMS with posterior–anterior (PA) and anterior–posterior (AP) current flow within the primary motor cortex evoke preferentially early and late I‐waves, respectively. Seventeen participants were instructed to stay at rest or to imagine maximal isometric contractions of the right flexor carpi radialis. We demonstrated that the increase of corticospinal excitability during MI is greater with PA than AP orientation. By using paired‐pulse stimulations, we confirmed that short‐interval intracortical inhibition (SICI) increased during MI in comparison to rest with PA orientation, whereas we found that it decreased with AP orientation. Overall, these results indicate that the pathways recruited by PA and AP orientations that generate early and late I‐waves are differentially modulated by MI. [ABSTRACT FROM AUTHOR]

Introduction: Obsessive-compulsive disorder (OCD) is a highly prevalent chronic disorder, often refractory to treatment. While remaining elusive, a full understanding of the pathophysiology of OCD is crucial to optimize treatment. Transcranial magnetic stimulation (TMS) is a noninvasive technique that, paired with other neurophysiological techniques, such as electromyography, allows for in vivo assessment of human corticospinal neurophysiology. It has been used in clinical populations, including comparisons of patients with OCD and control volunteers. Results are often contradictory, and it is unclear if such measures change after treatment. Here we summarize research comparing corticospinal excitability between patients with OCD and control volunteers, and explore the effects of treatment with repetitive TMS (rTMS) on these excitability measures. Methods: We conducted a systematic review and meta-analysis of casecontrol studies comparing various motor cortical excitability measures in patients with OCD and control volunteers. Whenever possible, we metaanalyzed motor cortical excitability changes after rTMS treatment. Results: From 1,282 articles, 17 reporting motor cortex excitability measures were included in quantitative analyses. Meta-analysis regarding cortical silent period shows inhibitory deficits in patients with OCD, when compared to control volunteers. We found no statistically significant differences in the remaining meta-analyses, and no evidence, in patients with OCD, of pre- to post-rTMS changes in resting motor threshold, the only excitability measure for which longitudinal data were reported. Discussion: Our work suggests an inhibitory deficit of motor cortex excitability in patients with OCD when compared to control volunteers. Cortical silent period is believed to reflect activity of GABAB receptors, which is in line with neuroimaging research, showing GABAergic deficits in patients with OCD. Regardless of its effect on OCD symptoms, rTMS apparently does not modify Resting Motor Threshold, possibly because this measure reflects glutamatergic synaptic transmission, while rTMS is believed to mainly influence GABAergic function. Our meta-analyses are limited by the small number of studies included, and their methodological heterogeneity. Nonetheless, cortical silent period is a reliable and easily implementable measurement to assess neurophysiology in humans, in vivo. The present review illustrates the importance of pursuing the study of OCD pathophysiology using cortical silent period and other easily accessible, non-invasive measures of cortical excitability. [ABSTRACT FROM AUTHOR]

The Coronavirus disease 2019 (COVID-19), an illness caused by a SARS-CoV-2 viral infection, has been associated with neurological and neuropsychiatric disorders, revealing its impact beyond the respiratory system. Most related research involved individuals with post-acute or persistent symptoms of COVID-19, also referred to as long COVID or Post-Acute Sequelae of COVID-19 (PASC). In this longitudinal unique report, we aimed to describe the acute supraspinal and corticospinal changes and functional alterations induced by a COVID-19 infection using neuroimaging, neurophysiological and clinical assessment of a participant during acute infection, as compared to three other visits where the participant had no COVID-19. The results favor a multisystem impairment, impacting cortical activity, functional connectivity, and corticospinal excitability, as well as motor and cardiovascular function. The report suggests pathophysiological alteration and impairment already present at the acute stage, that if resolved tend to lead to a full clinical recovery. Such results could be also insightful into PASC symptomatology. • SARS-CoV-2 infection results in acute multisystem alterations. • Acute supraspinal changes involve cortical activity and connectivity alterations. • Increased cortical sensorimotor activity allows normal task performance. • Corticospinal excitability increases parallels GABAergic dysregulation. • Clinical recovery potentially promoted by pathophysiological processes resolution. [ABSTRACT FROM AUTHOR]

Evidence continues to accumulate that acute aerobic exercise (AAE) impacts neurophysiological excitability as measured by transcranial magnetic stimulation (TMS). Yet, uncertainty exists about which TMS measures are modulated after AAE in young adults. The influence of AAE intensity and duration of effects are also uncertain. This pre-registered meta-analysis (CRD42017065673) addressed these uncertainties by synthesizing data from 23 studies (including 474 participants) published until February 2024. Meta-analysis was run using a random-effects model and Hedge's g used as effect size. Our results demonstrated a decrease in short-interval intracortical inhibition (SICI) following AAE (g = 0.27; 95 % CI [0.16–0.38]; p <.0001), particularly for moderate (g = 0.18; 95 % CI [0.05–0.31]; p <.01) and high (g = 0.49; 95 % CI [0.27–0.71]; p <.0001) AAE intensities. These effects remained for 30 minutes after AAE. Additionally, increased corticospinal excitability was only observed for high intensity AAE (g = 0.28; 95 % CI, [0.07–0.48]; p <.01). Our results suggest potential mechanisms for inducing a more susceptible neuroplastic environment following AAE. • Acute aerobic exercise (AAE) decreases intracortical inhibition in young adults. • Short-interval intracortical inhibition (SICI) consistently decreased after AAE. • Moderate and high intensity AAE importantly contributes to the decrease in SICI. • Overall, AAE did not increase corticospinal excitability in young adults. • Corticospinal excitability was only increased after high intensity AAE. [ABSTRACT FROM AUTHOR]