Identifying and Assessing Inter-Muscular Fat at the Distal Diaphyseal Femur Measured by Peripheral Quantitative Computed Tomography (pQCT).

INTRODUCTION: Inter-/intramuscular fat can be assessed with peripheral Quantitative Computed Tomography (pQCT) and is of interest as an indicator of "muscle quality." Typical pQCT scan sites (forearm, lower leg) have a low amount of inter-/intramuscular fat, however distal diaphyseal femur scan sites with conspicuous inter-/intramuscular fat have been identified as potentially more prudent scan sites, even in healthy adolescents. However, current state of the art analysis methods require labor-intensive manual segmentation of the scan. The purpose of the present study was to evaluate the reliability of a novel open source automated enclosing convex polygon approach (source code https://github.com/tjrantal/pQCT, commit cec9bce) to quantify inter-/intramuscular fat from femoral pQCT scans in healthy adults. METHODOLOGY: The distal diaphyseal femur (25% of tibial length from the knee joint towards the hip) of 27 adults aged 18-50 yr were scanned twice, 1 wk apart, using pQCT. Subcutaneous fat, muscle, inter-/intramuscular fat, and marrow areas, and corresponding densities were evaluated using a method we have reported previously, as well as the novel enclosing convex polygon method. RESULTS: The session-to-session reliability of the assessments was fair to excellent using the previously reported method as indicated by intraclass correlation coefficient (ICC2,1) ranging from 0.45 to 1.00, while the novel method produced excellent reliability (ICC2,1 0.78-1.00). CONCLUSION: Distal diaphyseal femur appears to be a potentially informative and prudent scan site for inter-/intramuscular fat evaluation with pQCT.

The effects of verbal cueing for high intended movement velocity on power, neuromuscular activation, and performance.

It is widely believed that lifting heavy loads slowly, but with a conscious intention to move at high velocity, can produce resistance training (RT) adaptations indicative of rapid movements. This study investigated the effects of verbally cued high "intended" movement velocity (HIMV) during RT on neuromuscular and performance outcomes. 20 untrained volunteers (aged 24.2 ± 3.9 years) participated in 3 weeks of knee extension training. Participants were randomly allocated to receive verbal cues focusing on high intended movement velocity, HIMV, or steady and controlled movement, TRAD (traditional training). All other training variables, including actual movement velocity (30° s-1 ), remained constant. Increase in mean power output at 30° s-1 was greater for TRAD than HIMV (76% and 33%, respectively, P = 0.027). There were main effects for time (but no between-group differences) for maximal isometric force (+14%, P = 0.003), peak torque at 180° s-1 (+22%, P = 0.006), peak torque at 30° s-1 (+29%, P < 0.001), 3-repetition maximum (+20%, P < 0.001), and resting corticospinal excitability (+43%, P = 0.017). There were no differences between groups or across time for voluntary activation (P = 0.793), spinal excitability (P = 0.686), or intracortical inhibition (all P > 0.05). HIMV verbal cueing did not produce additional neurophysiological or performance benefits when compared to traditional cueing. Overall, our results demonstrated that verbal cueing did not alter the principle of velocity-specific adaptation. Cueing that increases the duration of maximal effort may be optimal for maximizing average power output at low speeds.

Investigating the effects of muscle contraction and conditioning stimulus intensity on short-interval intracortical inhibition.

A reduction in short-interval intracortical inhibition (SICI) has been shown to accompany acute or chronic resistance exercise; however, little is known about how SICI is modulated under different contraction intensities. Therefore, the purpose of this study was to assess the effect of muscle contraction and conditioning stimulus intensity on the modulation of SICI. Single- and paired-pulse transcranial magnetic stimulation was applied to the primary motor cortex (M1), and motor evoked potentials (MEPs) were recorded from the biceps brachii in 16 adults (10M/6F). A conditioning-test stimulus paradigm (3 ms inter-stimulus intervals) was delivered during 10%, 20%, 40% and 75% of maximal voluntary isometric contraction (MVIC). At each force level, conditioning stimulus intensities of 60%, 70% and 80% of active motor threshold (AMT) were tested. Single-pulse MEPs were expressed as a proportion of the maximal muscle compound action potential, while SICI was quantified as a ratio of the unconditioned MEP. MEP amplitude increased with force output, with the greatest increase at 75% of MVIC. A reduction in SICI was observed from 40% to 75% of MVIC, but not 10%-40% of MVIC. There was no significant interaction between conditioning stimulus intensity and force level. The conditioning stimulus intensity (60%, 70% or 80% of AMT) did not alter the modulation of SICI. SICI was reduced at 75% of MVIC compared with the lower force outputs, and the magnitude of SICI in individual participants at different force outputs was not related. The findings suggest that strong muscle contractions are accompanied by less inhibition, which may have implications for neuroplasticity in exercise interventions.

Effects of eccentric versus concentric contractions of the biceps brachii on intracortical inhibition and facilitation.

Differences in the neural mechanisms underpinning eccentric (ECC) and concentric (CON) contractions exist; however, the acute effects of fatiguing muscle contractions on intracortical and corticospinal excitability are not well understood. Therefore, we compared maximal ECC and CON contractions of the right biceps brachii (BB) muscle for changes in corticospinal excitability, short- (SICI) and long-interval intracortical inhibition (LICI) and intracortical facilitation (ICF) up to 1 hour post-exercise. Fourteen right-handed adults (11 M/3F; 26.8 ± 2.9 year) undertook a single session of 3 sets of 10 maximal ECC or CON contractions (180-second rest between sets) on an isokinetic dynamometer (40°/s) separated by 1 week, in a randomized crossover study. Maximum voluntary isometric contraction torque (MVIC), maximal muscle compound waves (MMAX ), and motor-evoked potentials elicited through transcranial magnetic stimulation (TMS) were recorded via surface electromyography from the right BB. MVIC decreased (P < 0.001) immediately after ECC and CON contractions similarly, but the decrease was sustained at 1 hour post-ECC contractions only. MMAX was reduced immediately (P = 0.014) and 1 hour post-exercise (P = 0.019) only for ECC contractions. SICI and ICF increased immediately after ECC and CON contractions (P < 0.001), but LICI increased only after ECC contractions (P < 0.001), and these increases remained at 1 hour post-ECC contractions only. These findings suggest that ECC contractions induced a longer-lasting neuromodulatory effect on intracortical inhibition and facilitation, which could indicate a central compensatory response to peripheral fatigue.

Effects of acute resistance training modality on corticospinal excitability, intra-cortical and neuromuscular responses.

OBJECTIVE: Although neural adaptations from strength training are known to occur, the acute responses associated with heavy-strength (HST) and hypertrophy training (HYT) remain unclear. Therefore, we aimed to compare the acute behaviour of corticospinal responses following a single session of HST vs HYT over a 72-h period. METHODS: Fourteen participants completed a random counterbalanced, crossover study that consisted of a single HST session [5 sets × 3 repetition maximum (RM)], a HYT session (3 sets × 12 RM) of the leg extensors and a control session (CON). Single- and paired-pulse transcranial magnetic stimulation (TMS) was used to measure changes in motor-evoked potential (MEP) amplitude, corticospinal silent period (CSP), intra-cortical facilitation (ICF), short-interval intra-cortical inhibition (SICI) and long-interval intra-cortical inhibition (LICI). Additionally, maximal muscle compound wave (M MAX) of the rectus femoris (RF) and maximal voluntary isometric contraction (MVIC) of the leg extensors were taken. All measures were taken at baseline, immediately post and 2, 6, 24, 48 and 72 h post-training. RESULTS: A significant condition x time interaction was observed for MVIC (P = 0.001), M MAX (P = 0.003), MEP amplitude (P < 0.001) and CSP (P = 0.002). No differences were observed between HST and HYT for all neurophysiological measures. No changes in SICI, ICF and LICI were observed compared to baseline. CONCLUSION: Our results suggest that: (1) the acute behaviour of neurophysiological measures is similar between HST and HYT; and (2) the increase in corticospinal excitability may be a compensatory response to attenuate peripheral fatigue.

Anodal-tDCS applied during unilateral strength training increases strength and corticospinal excitability in the untrained homologous muscle.

Evidence suggests that the cross-transfer of strength following unilateral training may be modulated by increased corticospinal excitability of the ipsilateral primary motor cortex, due to cross-activation. Anodal-tDCS (a-tDCS) has been shown to acutely increase corticospinal excitability and motor performance, which may enhance this process. Therefore, we sought to examine changes in neural activation and strength of the untrained limb following the application of a-tDCS during a single unilateral strength training session. Ten participants underwent three conditions in a randomized, double-blinded crossover design: (1) strength training + a-tDCS, (2) strength training + sham-tDCS and (3) a-tDCS alone. a-tDCS was applied for 20 min at 2 mA over the right motor cortex. Unilateral strength training of the right wrist involved 4 × 6 wrist extensions at 70 % of maximum. Outcome measures included maximal voluntary strength, corticospinal excitability, short-interval intracortical inhibition, and cross-activation. We observed a significant increase in strength of the untrained wrist (5.27 %), a decrease in short-interval intracortical inhibition (-13.49 %), and an increase in cross-activation (15.71 %) when strength training was performed with a-tDCS, but not following strength training with sham-tDCS, or tDCS alone. Corticospinal excitability of the untrained wrist increased significantly following both strength training with a-tDCS (17.29 %), and a-tDCS alone (15.15 %), but not following strength training with sham-tDCS. These findings suggest that a single session of a-tDCS combined with unilateral strength training of the right limb increases maximal strength and cross-activation to the contralateral untrained limb.

Differences in the gut microbiome across typical ageing and in Parkinson's disease.

The microbiota-gut-brain axis' role in Parkinson's disease (PD) pathophysiology, and how this differs from typical ageing, is poorly understood. Presently, gut-bacterial diversity, taxonomic abundance and metabolic bacterial pathways were compared across healthy young (n = 22, 18-35 years), healthy older (n = 33, 50-80 years), and PD groups (n = 18, 50-80 years) using shotgun sequencing and compositional data analysis. Associations between the gut-microbiome and PD symptoms, and between lifestyle factors (fibre intake, physical activity, and sleep) and the gut-microbiome were conducted. Alpha-diversity did not differ between PD participants and older adults, whilst beta-diversity differed between these groups. Lower abundance of Butyricimonas synergistica, a butyrate-producer, was associated with worse PD non-motor symptoms in the PD group. Regarding typical ageing, Bifidobacterium bifidum, was greater in the younger compared to older group, with no difference between the older and PD group. Abundance of metabolic pathways related to butyrate production did not differ among the groups, while other metabolic pathways differed among the three groups. Sleep efficiency was positively associated with Roseburia inulinivorans in the older group. These results highlight the relevance of gut-microbiota to PD and that reduced butyrate-production may be involved with PD pathophysiology. Future studies should account for lifestyle factors when investigating gut-microbiomes across ageing and in PD. This article is part of the Special Issue on "Microbiome & the Brain: Mechanisms & Maladies".

A meta-analytical review of transcranial direct current stimulation parameters on upper limb motor learning in healthy older adults and people with Parkinson's disease.

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.

Acute Effects of High-Intensity Aerobic Exercise on Motor Cortical Excitability and Inhibition in Sedentary Adults.

Transcranial magnetic stimulation studies have demonstrated increased cortical facilitation and reduced inhibition following aerobic exercise, even when examining motor regions separate to the exercised muscle group. These changes in brain physiology following exercise may create favorable conditions for adaptive plasticity and motor learning. One candidate mechanism behind these benefits is the increase in brain-derived neurotropic factor (BDNF) observed following exercise, which can be quantified from a venous blood draw. The aim of this study was to investigate changes in motor cortex excitability and inhibition of the upper limb, and circulating BDNF, following high-intensity interval training (HIIT) on a stationary bicycle. Nineteen sedentary adults participated in a randomized crossover design study involving a single bout of high-intensity interval cycling for 20 min or seated rest. Venous blood samples were collected, and transcranial magnetic stimulation (TMS) was used to stimulate the extensor carpi radialis (ECR), where motor evoked potentials (MEP) were recorded pre- and post-condition. Following exercise, there was a significant increase (29.1%, p < 0.001) in corticospinal excitability measured at 120% of resting motor threshold (RMT) and a reduction in short-interval cortical inhibition (SICI quantified as 86.2% increase in the SICI ratio, p = 0.002). There was a non-significant (p = 0.125) 23.6% increase in BDNF levels. Collectively, these results reflect a net reduction in gamma aminobutyric acid (GABA)ergic synaptic transmission and increased glutamatergic facilitation, resulting in increased corticospinal excitability. This study supports the notion that acute high-intensity exercise provides a potent stimulus for inducing cortical neuroplasticity, which may support enhanced motor learning.

To the Gut Microbiome and Beyond: The Brain-First or Body-First Hypothesis in Parkinson's Disease.

There is continued debate regarding Parkinson's disease etiology and whether it originates in the brain or begins in the gut. Recently, evidence has been provided for both, with Parkinson's disease onset presenting as either a "body-first" or "brain-first" progression. Most research indicates those with Parkinson's disease have an altered gut microbiome compared to controls. However, some studies do not report gut microbiome differences, potentially due to the brain or body-first progression type. Based on the etiology of each proposed progression, individuals with the body-first progression may exhibit altered gut microbiomes, i.e., where short-chain fatty acid producing bacteria are reduced, while the brain-first progression may not. Future microbiome research should consider this hypothesis and investigate whether gut microbiome differences exist between each type of progression. This may further elucidate the impact of the gut microbiome in Parkinson's disease and show how it may not be homogenous across individuals with Parkinson's disease.

A Review of the Measurement of the Neurology of Gait in Cognitive Dysfunction or Dementia, Focusing on the Application of fNIRS during Dual-Task Gait Assessment.

Poor motor function or physical performance is a predictor of cognitive decline. Additionally, slow gait speed is associated with poor cognitive performance, with gait disturbances being a risk factor for dementia. Parallel declines in muscular and cognitive performance (resulting in cognitive frailty) might be driven primarily by muscle deterioration, but bidirectional pathways involving muscle-brain crosstalk through the central and peripheral nervous systems are likely to exist. Following screening, early-stage parallel declines may be manageable and modifiable through simple interventions. Gait-brain relationships in dementia and the underlying mechanisms are not fully understood; therefore, the current authors critically reviewed the literature on the gait-brain relationship and the underlying mechanisms and the feasibility/accuracy of assessment tools in order to identify research gaps. The authors suggest that dual-task gait is involved in concurrent cognitive and motor activities, reflecting how the brain allocates resources when gait is challenged by an additional task and that poor performance on dual-task gait is a predictor of dementia onset. Thus, tools or protocols that allow the identification of subtle disease- or disorder-related changes in gait are highly desirable to improve diagnosis. Functional near-infrared spectroscopy (fNIRS) is a non-invasive, cost-effective, safe, simple, portable, and non-motion-sensitive neuroimaging technique, widely used in studies of clinical populations such as people suffering from Alzheimer's disease, depression, and other chronic neurological disorders. If fNIRS can help researchers to better understand gait disturbance, then fNIRS could form the basis of a cost-effective means of identifying people at risk of cognitive dysfunction and dementia. The major research gap identified in this review relates to the role of the central/peripheral nervous system when performing dual tasks.

The Reliability of Neurological Measurement in the Vastus Medialis: Implications for Research and Practice.

The integrity of the corticomotor pathway is paramount in the optimal functioning of skeletal muscle. However, variability of neurophysiological assessment via peripheral nerve and transcranial magnetic stimulation can render interpretation difficult. Seldom evidence exists regarding the reliability of such measurements in the leg extensors, which have important locomotive and functional roles. This study aimed to assess the test-retest reliability of peripheral, corticospinal and intracortical responses in the vastus medialis. Transcranial magnetic and direct current electrical nerve stimulation were delivered to sixteen healthy young adults (8M and 8F) on two separate occasions. The Hoffmann reflex, maximal compound wave, motor evoked potential, corticospinal silent period, intracortical facilitation, and short-interval intracortical inhibition were recorded from the vastus medialis at rest, and during controlled submaximal voluntary contraction. Relative reliability was quantified using intra-class correlation coefficient (ICC2,1). Absolute reliability was quantified using standard error of measurement (SEm) and minimal detectable change (MDC). Corticospinal silent period, corticospinal silent period/motor evoked potential ratio, active motor evoked potential, maximal Hoffman reflex, and passive short-interval intracortical inhibition demonstrated "good to excellent" relative reliability (ICC ≥ 0.643). Intracortical facilitation demonstrated the lowest relative reliability (ICC = 0.420-0.908). Corticospinal silent period displayed the lowest absolute reliability (SEm ≤ 18.68%). Good reliability of the maximal compound wave, Hoffman reflex, motor evoked potential, and corticospinal silent period allow for reliable neurological evaluation of peripheral and corticospinal pathways in the vastus medialis. Future research should investigate reliability of the intracortical (short-interval intracortical inhibition and intracortical facilitation) measures by using different paired-pulse stimulus parameters. These findings hold important implications for neurophysiological assessment conducted in the leg extensor group.

Sensory manipulation results in increased dorsolateral prefrontal cortex activation during static postural balance in sedentary older adults: An fNIRS study.

BACKGROUND: The dorsolateral prefrontal cortex (DLPFC) is involved with allocating attentional resources to maintain postural control. However, it is unknown whether age-related structural and functional declines of the DLPFC may impair postural control during sensory manipulation. In this study, we aim to understand the effects of aging on the DLPFC when sensory cues were removed or presented inaccurately (i.e., increased sensory complexity) during the sensory orientation test (SOT). METHODS: Twenty young (18-25 years) and 18 older (66-73 years) healthy adults were recruited to undertake the SOT, which consisted of six conditions aimed at removing or disrupting the visual, vestibular, and proprioceptive senses. During these six SOT conditions, functional near-infrared spectroscopy (fNIRS), consisting of eight transmitter-receiver optode pairs (four channels over the left and right DLPFC), was used to measure hemodynamic responses (i.e., changes in oxy- [O2 Hb] and deoxyhemoglobin [HHb]) from the bilateral DLPFC. RESULTS: Our results show an increase in bilateral DLPFC activation (i.e., increase in O2 Hb and concomitant smaller decrease in HHb) with increasing sensory complexity in both young and older adults. The increase in left and right DLPFC activation during more complex sensory conditions was greater, which was concomitant with reduced balance performance in older adults compared to younger adults. Furthermore, we observed a right lateralized DLPFC activation in younger adults. Finally, a significant positive association was observed between balance performance and increased bilateral DLPFC activation particularly for SOT conditions with greater sensory disruptions. CONCLUSION: Our findings highlight the involvement of the DLPFC in maintaining postural control, particularly during complex sensory tasks, and provide direct evidence for the role of the DLPFC during postural control of a clinically relevant measure of balance.

The Cross-Education Phenomenon: Brain and Beyond.

Objectives: Unilateral resistance training produces strength gains in the untrained homologous muscle group, an effect termed "cross-education." The observed strength transfer has traditionally been considered a phenomenon of the nervous system, with few studies examining the contribution of factors beyond the brain and spinal cord. In this hypothesis and theory article, we aim to discuss further evidence for structural and functional adaptations occurring within the nervous, muscle, and endocrine systems in response to unilateral resistance training. The limitations of existing cross-education studies will be explored, and novel potential stakeholders that may contribute to the cross-education effect will be identified. Design: Critical review of the literature. Method: Search of online databases. Results: Studies have provided evidence that functional reorganization of the motor cortex facilitates, at least in part, the effects of cross-education. Cross-activation of the "untrained" motor cortex, ipsilateral to the trained limb, plays an important role. While many studies report little or no gains in muscle mass in the untrained limb, most experimental designs have not allowed for sensitive or comprehensive investigation of structural changes in the muscle. Conclusions: Increased neural drive originating from the "untrained" motor cortex contributes to the cross-education effect. Adaptive changes within the muscle fiber, as well as systemic and hormonal factors require further investigation. An increased understanding of the physiological mechanisms contributing to cross-education will enable to more effectively explore its effects and potential applications in rehabilitation of unilateral movement disorders or injury.

Cross-Activation of the Motor Cortex during Unilateral Contractions of the Quadriceps.

Transcranial magnetic stimulation (TMS) studies have demonstrated that unilateral muscle contractions in the upper limb produce motor cortical activity in both the contralateral and ipsilateral motor cortices. The increase in excitability of the corticomotor pathway activating the resting limb has been termed "cross-activation", and is of importance due to its involvement in cross-education and rehabilitation. To date, very few studies have investigated cross-activation in the lower limb. Sixteen healthy participants (mean age 29 ± 9 years) took part in this study. To determine the effect of varying contraction intensities in the lower limb, we investigated corticomotor excitability and intracortical inhibition of the right rectus femoris (RF) while the left leg performed isometric extension at 0%, 25%, 50%, 75% and 100% of maximum force output. Contraction intensities of 50% maximal force output and greater produced significant cross-activation of the corticomotor pathway. A reduction in silent period duration was observed during 75% and 100% contractions, while the release of short-interval intracortical inhibition (SICI) was only observed during maximal (100%) contractions. We conclude that increasing isometric contraction intensities produce a monotonic increase in cross-activation, which was greatest during 100% force output. Unilateral training programs designed to induce cross-education of strength in the lower limb should therefore be prescribed at the maximal intensity tolerable.

Corrigendum: Does a Combination of Virtual Reality, Neuromodulation and Neuroimaging Provide a Comprehensive Platform for Neurorehabilitation? - A Narrative Review of the Literature.

[This corrects the article on p. 284 in vol. 10, PMID: 27445739.].

Using non-invasive transcranial stimulation to improve motor and cognitive function in Parkinson's disease: a systematic review and meta-analysis.

Parkinson's disease (PD) is a neurodegenerative disorder affecting motor and cognitive abilities. There is no cure for PD, therefore identifying safe therapies to alleviate symptoms remains a priority. This meta-analysis quantified the effectiveness of repetitive transcranial magnetic stimulation (rTMS) and transcranial electrical stimulation (TES) to improve motor and cognitive dysfunction in PD. PubMed, EMBASE, Web of Science, Google Scholar, Scopus, Library of Congress and Cochrane library were searched. 24 rTMS and 9 TES studies (n = 33) with a sham control group were included for analyses. The Physiotherapy Evidence Database and Cochrane Risk of Bias showed high quality (7.5/10) and low bias with included studies respectively. Our results showed an overall positive effect in favour of rTMS (SMD = 0.394, CI [0.106-0.683], p = 0.007) and TES (SMD = 0.611, CI [0.188-1.035], p = 0.005) compared with sham stimulation on motor function, with no significant differences detected between rTMS and TES (Q [1] = 0.69, p = 0.406). Neither rTMS nor TES improved cognition. No effects for stimulation parameters on motor or cognitive function were observed. To enhance the clinical utility of non-invasive brain stimulation (NBS), individual prescription of stimulation parameters based upon symptomology and resting excitability state should be a priority of future research.