Training of a discrete motor skill in humans is accompanied by increased excitability of the fastest corticospinal connections at movement onset.

KEY POINTS: The primary motor cortex (M1) is fundamentally important for the acquisition of skilled motor behaviours. We tested the excitability changes of distinct M1 circuits at movement onset with TMS H-reflex conditioning. Human subjects trained a discrete spatiotemporal motor skill. Practice was associated with reduced kinematic variability and improved motor performance. Performance improvements were paralleled by task-specific excitability increases of the fastest corticospinal connections at infragranular layer 5b of M1. No task-related changes in excitability were observed at supragranular layers. Excitability changes in the fastest corticospinal connections were not directly related to changes in motor performance. ABSTRACT: The primary motor cortex (M1) is fundamentally important for the acquisition of skilled motor behaviours. Recent advances in imaging and electrophysiological techniques have improved our understanding of M1 neural circuit modulation in rodents and non-human primates during motor learning. However, little remains known about the learning-related changes of distinct elements in the human brain. In this study, we tested excitability changes of different neural circuits (infragranular and supragranular layers) in the M1 of human subjects who underwent training in a discrete spatiotemporal motor skill. Excitability modulations were assessed by recording H-reflex facilitation from transcranial magnetic stimulation at movement onset. Motor practice improved the consistency of movements and was accompanied by an excitability increase of the fastest corticospinal connections during the initial stages of motor practice. No such excitability changes were observed for training in a simple motor skill and circuits at supragranular layers of M1. Notably, changes in excitability were not associated with changes in motor performance. Our findings could reflect learning-related increases in the recruitment and/or reorganisation of the fastest corticospinal connections.

Evidence that distinct human primary motor cortex circuits control discrete and rhythmic movements.

KEY POINTS: Discrete and rhythmic dynamics are inherent components of (human) movements. We provide evidence that distinct human motor cortex circuits contribute to discrete and rhythmic movements. Excitability of supragranular layer circuits of the human motor cortex was higher during discrete movements than during rhythmic movements. Conversely, more complex corticospinal circuits showed higher excitability during rhythmic movements than during discrete movements. No task-specific differences existed for corticospinal output neurons at infragranular layers. The excitability differences were found to be time(phase)-specific and could not be explained by the kinematic properties of the movements. The same task-specific differences were found between the last cycle of a rhythmic movement period and ongoing rhythmic movements. ABSTRACT: Human actions entail discrete and rhythmic movements (DM and RM, respectively). Recent insights from human and animal studies indicate different neural control mechanisms for DM and RM, emphasizing the intrinsic nature of the task. However, how distinct human motor cortex circuits contribute to these movements remains largely unknown. In the present study, we tested distinct primary motor cortex and corticospinal circuits and proposed that they show differential excitability between DM and RM. Human subjects performed either 1) DM or 2) RM using their right wrist. We applied an advanced electrophysiological approach involving transcranial magnetic stimulation and peripheral nerve stimulation to test the excitability of the neural circuits. Probing was performed at different movement phases: movement initiation (MI, 20 ms after EMG onset) and movement execution (ME, 200 ms after EMG onset) of the wrist flexion. At MI, excitability at supragranular layers was significantly higher in DM than in RM. Conversely, excitability of more complex corticospinal circuits was significantly lower in DM than RM at ME. No task-specific differences were found for direct corticospinal output neurons at infragranular layers. The neural differences could not be explained by the kinematic properties of the movements and also existed between ongoing RM and the last cycle of RM. Our results therefore strengthen the hypothesis that different neural control mechanisms engage in DM and RM.

Non-invasive assessment of superficial and deep layer circuits in human motor cortex.

KEY POINTS: The first indirect (I) corticospinal volley from stimulation of the motor cortex consists of two parts: one that originates from infragranular layer 5 and a subsequent part with a delay of 0.6 ms to which supragranular layers contribute. Non-invasive probing of these two parts was performed in humans using a refined electrophysiological method involving transcranial magnetic stimulation and peripheral nerve stimulation. Activity modulation of these two parts during a sensorimotor discrimination task was consistent with previous results in monkeys obtained with laminar recordings. ABSTRACT: Circuits in superficial and deep layers play distinct roles in cortical computation, but current methods to study them in humans are limited. Here, we developed a novel approach for non-invasive assessment of layer-specific activity in the human motor cortex. We first conducted brain slice and in vivo experiments on monkey motor cortex to investigate the output timing from layer 5 (including corticospinal neurons) following extracellular stimulation. Neuron responses contained cyclical waves. The first wave was composed of two parts: the earliest part originated only from stimulation of layer 5; after 0.6 ms, stimuli to superficial layers 2/3 could also contribute. In healthy humans we then assessed different parts of the first corticospinal volley elicited by transcranial magnetic stimulation (TMS), by interacting TMS with stimulation of the median nerve generating an H-reflex. By adjusting the delay between stimuli, we could assess the earliest volley evoked by TMS, and the part 0.6 ms later. Measurements were made while subjects performed a visuo-motor discrimination task, which has been previously shown in monkey to modulate superficial motor cortical cells selectively depending on task difficulty. We showed a similar selective modulation of the later part of the TMS volley, as expected if this part of the volley is sensitive to superficial cortical excitability. We conclude that it is possible to segregate different cortical circuits which may refer to different motor cortex layers in humans, by exploiting small time differences in the corticospinal volleys evoked by non-invasive stimulation.

Assessing TMS-induced D and I waves with spinal H-reflexes.

Transcranial magnetic stimulation (TMS) of motor cortex produces a series of descending volleys known as D (direct) and I (indirect) waves. In the present study, we questioned whether spinal H-reflexes can be used to dissect D waves and early and late I waves from TMS. We therefore probed H-reflex facilitation at arrival times of D and I waves at the spinal level and thereby changed TMS parameters that have previously been shown to have selective effects on evoked D and different I waves. We changed TMS intensity and current direction and applied a double-pulse paradigm known as short-interval intracortical inhibition (SICI). Experiments were conducted in flexor carpi radialis (FCR) in the arm and soleus (SOL) in the leg. There were two major findings: 1) in FCR, H-reflex facilitation showed characteristic modulations with altered TMS parameters that correspond to the changes of evoked D and I waves; and 2) H-reflexes in SOL did not, possibly because of increased interference from other spinal circuits. Therefore, the most significant outcome of this study is that in FCR, H-reflexes combined with TMS seem to be a useful technique to dissect TMS-induced D and I waves. NEW & NOTEWORTHY Questions that relate to corticospinal function in pathophysiology and movement control demand sophisticated techniques to provide information about corticospinal mechanisms. We introduce a noninvasive electrophysiological technique that may be useful in describing such mechanisms in more detail by dissecting D and I waves from transcranial magnetic stimulation (TMS). Based on the combination of spinal H-reflexes and TMS in the flexor carpi radialis muscle, the technique was shown to measure selective effects on D and I waves from changing TMS parameters.

Evidence for a subcortical contribution to intracortical facilitation.

Intracortical facilitation (ICF) describes the facilitation of an EMG response (motor evoked potential) to a suprathreshold pulse (S2) of transcranial magnetic stimulation (TMS) by a preceding subthreshold pulse (S1) given 10-15 ms earlier. ICF is widely assumed to originate from intracortical mechanisms. In this study, we used spinal H-reflexes to test whether subcortical mechanisms can also contribute to the facilitation. Measurements were performed in the upper limb muscle flexor carpi radialis in 17 healthy volunteers, and in the lower limb muscle soleus in 16 healthy volunteers. S2 given alone facilitated the H-reflex. When S1 preceded S2 by 10 ms, the amount of facilitation increased, compatible with ICF. However, S1 given alone also facilitated the H-reflex, suggesting that it had evoked descending activity even though its intensity was well below resting motor threshold. Across participants, the amount of H-reflex facilitation from S1 alone was proportional to the degree of H-reflex facilitation with combined S1-S2. These results indicate that subcortical mechanisms can contribute to ICF and potentially add to the variability of the ICF measure reported in previous studies.

Perceived Benefit and Satisfaction With a Tablet Computer and an Emergency Smartwatch by Older Adults and Their Relatives: Prospective Real-World Pilot Study.

Background: Assistive technologies (ATs) have the potential to promote the quality of life and independent living of older adults and, further, to relieve the burden of formal and informal caregivers and relatives. Technological developments over the last decades have led to a boost of available ATs. However, evidence on the benefits and satisfaction with ATs in real-world applications remains scarce. Objective: This prospective, real-world, pilot study tested the perceived benefit and satisfaction with different ATs in the real-world environment. Methods: Community-dwelling adults aged ≥65 and their relatives tested a tablet computer with a simplified interface or a smartwatch with programmable emergency contacts for 8 weeks in their everyday life. Perceived benefits and satisfaction with ATs were assessed by all older adults and their relatives using different assessment tools before and after the intervention. Outcome measures included the Technology Usage Inventory, Quebec User Evaluation of Satisfaction with Assistive Technology 2.0, and Canadian Occupational Performance Measure. Results: A total of 17 older adults (tablet computer: n=8, 47% and smartwatch: n=9, 53%) and 16 relatives (tablet computer: n=7, 44% and smartwatch: n=9, 56%) were included in the study. The number of participants that were frail (according to the Clinical Frailty Scale) and received care was higher in the smartwatch group than in the tablet computer group. Older adults of the smartwatch group reported higher technology acceptance (Technology Usage Inventory) and satisfaction (Quebec User Evaluation of Satisfaction with Assistive Technology 2.0) scores than those of the tablet computer group, although the differences were not significant (all P>.05). In the tablet computer group, relatives had significantly higher ratings on the item intention to use than older adults (t12.3=3.3, P=.006). Identified everyday issues with the Canadian Occupational Performance Measure included contact/communication and entertainment/information for the tablet computer, safety and getting help in emergency situations for the smartwatch, and the usability of the AT for both devices. While the performance (t8=3.5, P=.008) and satisfaction (t8=3.2, P=.01) in these domains significantly improved in the smartwatch group, changes in the tablet computer group were inconsistent (all P>.05). Conclusions: This study highlights the remaining obstacles for the widespread and effective application of ATs in the everyday life of older adults and their relatives. While the results do not provide evidence for a positive effect regarding communication deficits, perceived benefits could be shown for the area of safety. Future research and technical developments need to consider not only the preferences, problems, and goals of older adults but also their relatives and caregivers to improve the acceptability and effectiveness of ATs.

Effects of dynamic and isometric motor practice on position control, force control and corticomuscular coherence in preadolescent children.

In this study, we investigated the effects of motor practice with an emphasis on either position or force control on motor performance, motor accuracy and variability in preadolescent children. Furthermore, we investigated corticomuscular coherence and potential changes following motor practice. We designed a setup allowing discrete wrist flexions of the non-dominant hand and tested motor accuracy and variability when the task was to generate specific movement endpoints (15-75 deg) or force levels (5-25% MVC). All participants were tested in both tasks at baseline and post motor practice without augmented feedback on performance. Following baseline assessment, participants (44 children aged 9-11 years) were randomly assigned to either position (PC) or force control (FC) motor practice or a resting control group (CON). The PC and FC groups performed four blocks of 40 trials motor practice with augmented feedback on performance. Following practice, improvements in movement accuracy were significantly greater in the PC group compared to the FC and CON groups (p < 0.001). None of the groups displayed changes in force task performance indicating no benefits of force control motor practice and low transfer between tasks (p-values:0.08-0.45). Corticomuscular coherence (C4-FCR) was demonstrated during the hold phase in both tasks with no difference between tasks. Corticomuscular coherence did not change from baseline to post practice in any group. Our findings demonstrate that preadolescent children improve position control following dynamic accuracy motor practice. Contrary to previous findings in adults, preadolescent children displayed smaller or no improvements in force control following isometric motor practice, low transfer between tasks and no changes in corticomuscular coherence.

Dynamic motor practice improves movement accuracy, force control and leads to increased corticospinal excitability compared to isometric motor practice.

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 between-task 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.

Trial-to-trial Variability and Cortical Processing Depend on Recent Outcomes During Human Reinforcement Motor Learning.

The history of our actions and their outcomes represent important information, informing choices and efficiently guiding future behavior. While unsuccessful (S-) outcomes are expected to lead to more explorative motor states and increased behavioral variability, successful (S+) outcomes are expected to reinforce the use of the previous action. Here, we show that humans attribute different values to previous actions during reinforcement motor learning when they experience S- compared to S+ outcomes. Behavioral variability after an S- outcome is influenced more by the previous outcome than after S+ outcomes. Using electroencephalography, we show that theta band oscillations of the prefrontal cortex are most prominent during changes in two consecutive outcomes, potentially reflecting the need for enhanced cognitive control. Our results suggest that S+ experiences 'overwrite' previous motor states to a greater extent than S- experiences and that modulations in neural oscillations in the prefrontal cortex play a potential role in encoding changes in movement variability state during reinforcement motor learning.

Correction to: Effects of Blood Flow Restriction Training on Muscular Strength and Hypertrophy in Older Individuals: A Systematic Review and Meta-Analysis.

Figures 2 and 3 were transposed.

Effects of Blood Flow Restriction Training on Muscular Strength and Hypertrophy in Older Individuals: A Systematic Review and Meta-Analysis.

BACKGROUND: The combination of low-load resistance training with blood flow restriction (BFR) has recently been shown to promote muscular adaptations in various populations. To date, however, evidence is sparse on how this training regimen influences muscle mass and strength in older adults. PURPOSE: The purpose of this systematic review and meta-analysis was to quantitatively identify the effects of low-load BFR (LL-BFR) training on muscle mass and strength in older individuals in comparison with conventional resistance training programmes. Additionally, the effectiveness of walking with and without BFR was assessed. METHODS: A PRISMA-compliant systematic review and meta-analysis was conducted. The systematic literature research was performed in the following electronic databases from inception to 1 June 2018: PubMed, Web of Science, Scopus, CINAHL, SPORTDiscus and CENTRAL. Subsequently, a random-effects meta-analysis with inverse variance weighting was conducted. RESULTS: A total of 2658 articles were screened, and 11 studies with a total population of N = 238 were included in the meta-analysis. Our results revealed that during both low-load training and walking, the addition of BFR elicits significantly greater improvements in muscular strength with pooled effect sizes (ES) of 2.16 (95% CI 1.61 to 2.70) and 3.09 (95% CI 2.04 to 4.14), respectively. Muscle mass was also increased when comparing walking with and without BFR [ES 1.82 (95% CI 1.32 to 2.32)]. In comparison with high-load training, LL-BFR promotes similar muscle hypertrophy [ES 0.21 (95% CI - 0.14 to 0.56)] but lower strength gains [ES - 0.42 (95% CI - 0.70 to - 0.14)]. CONCLUSION: This systematic review and meta-analysis reveals that LL-BFR and walking with BFR is an effective interventional approach to stimulate muscle hypertrophy and strength gains in older populations. As BFR literature is still scarce with regard to potential moderator variables (e.g. sex, cuff pressure or training volume/frequency), further research is needed for strengthening the evidence for an effective application of LL-BFR training in older people.

Applications of Functional Near-Infrared Spectroscopy (fNIRS) Neuroimaging in Exercise⁻Cognition Science: A Systematic, Methodology-Focused Review.

For cognitive processes to function well, it is essential that the brain is optimally supplied with oxygen and blood. In recent years, evidence has emerged suggesting that cerebral oxygenation and hemodynamics can be modified with physical activity. To better understand the relationship between cerebral oxygenation/hemodynamics, physical activity, and cognition, the application of state-of-the art neuroimaging tools is essential. Functional near-infrared spectroscopy (fNIRS) is such a neuroimaging tool especially suitable to investigate the effects of physical activity/exercises on cerebral oxygenation and hemodynamics due to its capability to quantify changes in the concentration of oxygenated hemoglobin (oxyHb) and deoxygenated hemoglobin (deoxyHb) non-invasively in the human brain. However, currently there is no clear standardized procedure regarding the application, data processing, and data analysis of fNIRS, and there is a large heterogeneity regarding how fNIRS is applied in the field of exercise⁻cognition science. Therefore, this review aims to summarize the current methodological knowledge about fNIRS application in studies measuring the cortical hemodynamic responses during cognitive testing (i) prior and after different physical activities interventions, and (ii) in cross-sectional studies accounting for the physical fitness level of their participants. Based on the review of the methodology of 35 as relevant considered publications, we outline recommendations for future fNIRS studies in the field of exercise⁻cognition science.

Functional near-infrared spectroscopy in movement science: a systematic review on cortical activity in postural and walking tasks.

Safe locomotion is a crucial aspect of human daily living that requires well-functioning motor control processes. The human neuromotor control of daily activities such as walking relies on the complex interaction of subcortical and cortical areas. Technical developments in neuroimaging systems allow the quantification of cortical activation during the execution of motor tasks. Functional near-infrared spectroscopy (fNIRS) seems to be a promising tool to monitor motor control processes in cortical areas in freely moving subjects. However, so far, there is no established standardized protocol regarding the application and data processing of fNIRS signals that limits the comparability among studies. Hence, this systematic review aimed to summarize the current knowledge about application and data processing in fNIRS studies dealing with walking or postural tasks. Fifty-six articles of an initial yield of 1420 publications were reviewed and information about methodology, data processing, and findings were extracted. Based on our results, we outline the recommendations with respect to the design and data processing of fNIRS studies. Future perspectives of measuring fNIRS signals in movement science are discussed.

Brain activity during walking: A systematic review.

BACKGROUND: This systematic review provides an overview of the literature deducing information about brain activation during (1) imagined walking using MRI/fMRI or (2) during real walking using measurement systems as fNIRS, EEG and PET. METHODS: Three independent reviewers undertook an electronic database research browsing six databases. The search request consisted of three search fields. The first field comprised common methods to evaluate brain activity. The second search field comprised synonyms for brain responses to movements. The third search field comprised synonyms for walking. RESULTS: 48 of an initial yield of 1832 papers were reviewed. We found differences in cortical activity regarding young vs. old individuals, physically fit vs. physically unfit cohorts, healthy people vs. patients with neurological diseases, and between simple and complex walking tasks. CONCLUSIONS: We summarize that the dimension of brain activity in different brain areas during walking is highly sensitive to task complexity, age and pathologies supporting previous assumptions underpinning the significance of cortical control. Many compensation mechanisms reflect the brain's plasticity which ensures stable walking.