A novel biomechanical indicator for impaired ankle dorsiflexion function during walking in individuals with chronic stroke.

BACKGROUND: Ankle dorsiflexion function during swing phase contributes to foot clearance and plays an important role in walking ability post-stroke. Commonly used biomechanical measures such as foot clearance and ankle joint excursion have limited ability to accurately evaluate impaired dorsiflexor function. RESEARCH QUESTION: Can ankle angular velocity and acceleration be used as reliable measurers of dorsiflexion function in post-stroke gait? METHODS: Using linear regression and Pearson's correlation we retrospectively compared peak ankle angular velocity (AωP), peak ankle angular acceleration (AαP), peak dorsiflexion angle (DFAP) and peak foot clearance (FCLP) as direct measures for swing phase dorsiflexor function in 60 chronic stroke survivors. Intraclass correlation coefficient (ICC) analysis was used for test-retest reliability of AωP and AαP. RESULTS: Linear regression models revealed that AωP, AαP, DFAP, FCLP had a significant relationship (p < 0.05) with impaired dorsiflexion function. AαP and DFAP accounted for the most variance of dorsiflexion function. AωP, AαP, FCLP, correlated significantly with all clinical outcome measures of walking ability. DFAP had a positive correlation only with FMA-LE. Post-hoc William's t-tests, used to compare the magnitude of difference between two non-independent correlations, revealed that the correlation between all clinical measures and DFAP were significantly weaker than with AωP and AαP. Correlation between FMA-LE and FCLP was weaker than with AωP and AαP. Excellent test-retest reliability for both AωP (ICC = 0.968) and AαP (ICC = 0.947) was observed. SIGNIFICANCE: These results suggest that DFAP may only be associated with dorsiflexion function during non-task specific isolated movements, but not during walking. FCLP is associated with dorsiflexion function and walking ability measures but not as strongly as AωP and AαP possibly because FCLP is influenced by contribution from hip and knee joint movements. Therefore, AωP and AαP are reliable measures and represent dorsiflexion function more accurately than DFAP, and FCLP.

Systematic Evaluation of the Effects of Voluntary Activation on Lower Extremity Motor Thresholds.

The purpose of this investigation was to elucidate the relationship between the resting motor threshold (rMT) and active motor threshold (aMT). A cross-sectional comparison of MTs measured at four states of lower extremity muscle activation was conducted: resting, 5% maximal voluntary contraction (MVC), 10%MVC, and standing. MTs were measured at the tibialis anterior in the ipsilesional and contralesional limbs in participants in the chronic phase (>6 months) of stroke (n = 11) and in the dominant limb of healthy controls (n = 11). To compare across activation levels, the responses were standardized using averaged peak-to-peak background electromyography (EMG) activity measured at 10%MVC + 2SD for each participant, in addition to the traditional 0.05 mV criterion for rMT (rMT50). In all participants, as muscle activation increased, the least square mean estimates of MTs decreased (contralesional: p = 0.008; ipsilesional: p = 0.0015, healthy dominant: p < 0.0001). In healthy controls, rMT50 was significantly different from all other MTs (p < 0.0344), while in stroke, there were no differences in either limb (p > 0.10). This investigation highlights the relationship between rMT and aMTs, which is important as many stroke survivors do not present with an rMT, necessitating the use of an aMT. Future works may consider the use of the standardized criterion that accounted for background EMG activity across activation levels.

A novel biomechanical indicator for impaired ankle dorsiflexion function during walking in individuals with chronic stroke.

Ankle dorsiflexion function during swing phase of the gait cycle contributes to foot clearance and plays an important role in walking ability post-stroke. Commonly used biomechanical measures such as foot clearance and ankle joint excursion have limited ability to accurately evaluate dorsiflexor function in stroke gait. We retrospectively evaluated ankle angular velocity and ankle angular acceleration as direct measures for swing phase dorsiflexor function in post-stroke gait of 61 chronic stroke survivors. Our linear regression models revealed that peak ankle angular velocity (AAV P ), peak ankle angular acceleration (AAA P ), peak dorsiflexion angle (DFA P ) and peak foot clearance (FCL P ) during swing had a significant relationship (p < 0.05) with impaired dorsiflexion function. AAA P and DFA P accounted for the most variance of dorsiflexion function. Additionally, AAV P , AAA P , FCL P during swing, correlated significantly with all clinical outcome measures of walking ability. DFA P during swing had a positive correlation only with FMA-LE. Post-hoc William's t -tests, used to compare the magnitude of difference between two non-independent correlations, revealed that the correlation between all clinical measures and DFA P were significantly weaker than with AAV P and AAA P . We also found that correlation between FMA-LE and FCL P was weaker than with AAV P and AAA P . We found an excellent test-retest reliability for both AAV P (ICC = 0.968) and AAA P (ICC = 0.947). These results suggest that DFA P may only be associated with non-task specific isolated dorsiflexion movement, but not during walking. FCL P is associated with dorsiflexion function and walking ability measures but not as strongly as AAV P and AAA P possibly because FCL P is influenced by contribution from hip and knee joint movements during walking. Therefore, we believe that AAV P and AAA P both can be used as reliable measures of impaired dorsiflexion function in post-stroke gait.

Interhemispheric Asymmetries in Intracortical Facilitation Correlate With Fatigue Severity in Individuals With Poststroke Fatigue.

PURPOSE: Poststroke fatigue (PSF) contributes to increased mortality and reduces participation in rehabilitative therapy. Although PSF's negative influences are well known, there are currently no effective evidence-based treatments for PSF. The lack of treatments is in part because of a dearth of PSF pathophysiological knowledge. Increasing our understanding of PSF's causes may facilitate and aid the development of effective therapies. METHODS: Twenty individuals, >6 months post stroke, participated in this cross-sectional study. Fourteen participants had clinically relevant pathological PSF, based on fatigue severity scale (FSS) scores (total score ≥36). Single-pulse and paired-pulse transcranial magnetic stimulation were used to measure hemispheric asymmetries in resting motor threshold, motor evoked potential amplitude, and intracortical facilitation (ICF). Asymmetry scores were calculated as the ratios between lesioned and nonlesioned hemispheres. The asymmetries were then correlated (Spearman rho) to FSS scores. RESULTS: In individuals with pathological PSF (N = 14, range of total FSS scores 39-63), a strong positive correlation (rs = 0.77, P = 0.001) between FSS scores and ICF asymmetries was calculated. CONCLUSIONS: As the ratio of ICF between the lesioned and nonlesioned hemispheres increased so did self-reported fatigue severity in individuals with clinically relevant pathological PSF. This finding may implicate adaptive/maladaptive plasticity of the glutamatergic system/tone as a contributor to PSF. This finding also suggests that future PSF studies should incorporate measuring facilitatory activity and behavior in addition to the more commonly studied inhibitory mechanisms. Further investigations are required to replicate this finding and identify the causes of ICF asymmetries.

Transcranial Direct Current Stimulation Electrode Montages May Differentially Impact Variables of Walking Performance in Individuals Poststroke: A Preliminary Study.

PURPOSE: Transcranial direct current stimulation (tDCS) has mixed effects on walking performance in individuals poststroke. This is likely the result of variations in tDCS electrode montages and individualized responses. The purpose of this study was to quantify the effects of a single session of tDCS using various electrode montages on poststroke walking performance. METHODS: Individuals with chronic stroke ( n = 16) participated in a double-blind, randomized cross-over study with sham stimulation and three tDCS electrode montages. Gait speed, paretic step ratio, and paretic propulsion were assessed prestimulation and poststimulation at self-selected and fastest comfortable speeds. Changes in muscle activation patterns with self-selected walking were quantified by the number of modules derived from nonnegative matrix factorization of EMG signals for hypothesis generation. RESULTS: There was no significant effect of active stimulation montages compared with sham. Comparisons between each participant's best response to tDCS and sham show personalized tDCS may have a positive effect on fastest comfortable overground gait speed ( P = 0.084), paretic step ratio ( P = 0.095) and paretic propulsion ( P = 0.090), and self-selected paretic step ratio ( P = 0.012). Participants with two or three modules at baseline increased module number in response to the all experimental montages and sham, but responses were highly variable. CONCLUSIONS: A single session of tDCS may affect clinical and biomechanical walking performance, but effects seem to be dependent on individual response variability to different electrode montages. Findings of this study are consistent with responses to various tDCS electrode montages being the result of underlying neuropathology, and the authors recommend examining how individual factors affect responses to tDCS.

The effects of chronic Δ-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) use on cerebral glucose metabolism in multiple sclerosis: a pilot study.

This exploratory pilot study investigated the effects of chronic Δ-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) on cerebral glucose metabolism in people with multiple sclerosis (PwMS). Compared with nonusers, THC users had hypermetabolism of 3 regions (p < 0.039, d >1.17) in left temporal areas, while CBD users had hypometabolism of 5 regions (p < 0.032, d > 1.31) in left temporal areas. This study highlights the need to discriminate between THC and CBD in future cannabis studies. Novelty Chronic THC and CBD use had disparate effects on cerebral glucose metabolism in PwMS.

Multiple Sclerosis, Cannabis Use, and Clinical Disability: A Preliminary [18F]-Fluorodeoxyglucose Positron Emission Tomography Study.

Introduction: Long-term consequences of medicinal cannabis use in people with multiple sclerosis (PwMS) are unknown. This study investigated whether PwMS using cannabis had lower resting brain glucose uptake (GU) and worse clinical test results compared with nonusers. Methods: Sixteen PwMS, eight users, underwent clinical testing followed by [18F]-Fluorodeoxyglucose positron emission tomography/computed tomography imaging. Results: Users had lower cognitive function test scores, but performed similarly on the other clinical evaluations. Accounting for disease duration, resting brain GU was similar between the groups. Conclusions: Lower cognitive function was not associated with resting brain GU. Cognitive dysfunction may be a contraindication or consequence of cannabis use in PwMS.

Functional factors that are important correlates to physical activity in people with multiple sclerosis: a pilot study.

PURPOSE: Identify functional factors that are important correlates to physical activity levels among people with multiple sclerosis. METHODS: A total of eight functional tests were conducted and physical activity was objectively measured (Actigraph GT3X accelerometer) for one week in 34 people with multiple sclerosis. A corrected Akaike Information Criterion analysis was performed to identify the strongest correlates with moderate-to-vigorous physical activity, total activity and sedentary time. RESULTS: The multiple regression analysis converged on a model for moderate-to-vigorous physical activity (R2 = 0.31, F = 6.97, p= 0.003) that included total strength of the less-affected leg (partial r = 0.46, p = 0.007) and average peg test performance (partial r = -0.30, p = 0.087). The model for total activity (R2 = 0.40, F = 10.51, p < 0.001) included five times sit-to-stand performance (partial r= -0.44, p = 0.010) and total strength of the less-affected leg (partial r = 0.31, p = 0.077). The model for sedentary time (R2=0.22, F = 9.23, p = 0.005) only included total strength of the more affected leg (r= -0.47, p = 0.005). CONCLUSION: These results suggest that leg strength, manual dexterity and the ability to perform functional tasks may be important correlates with physical activity levels in people with multiple sclerosis. The findings of this pilot study can inform future investigations aiming to increase physical activity levels or develop improved rehabilitation protocols for people with multiple sclerosis. Implications for Rehabilitation Physical activity is an effective means of improving the symptoms associated with multiple sclerosis. Participation in physical activity by people with multiple sclerosis may be affected by functional factors such as leg strength, manual dexterity and the ability to rise from a seated position. Bilateral leg strength differences should be assessed and addressed in people with multiple sclerosis.

Metabolic imaging in exercise physiology.

This minireview focuses on selected, noninvasive imaging techniques that have been used in the study of exercise physiology. These imaging modalities can be roughly divided into two categories: tracer based and nontracer based. Tracer-based methods use radiolabeled substrates whose location and quantity can subsequently be imaged once they are incorporated into metabolic processes. Nontracer-based imaging modalities rely on specific properties of substrates to identify metabolites and determine their concentrations. Identification and quantification of metabolites is usually based on magnetic properties or on differences in light absorption. In this review, we will highlight two tracer-based imaging modalities, positron emission tomography and single-photon-emission computed tomography, as well as two nontracer-based methods, magnetic resonance spectroscopy and near-infrared spectroscopy. Some of the recent findings that each technique has provided on cerebral and skeletal muscle metabolism during exercise, as well as the strengths and limitations of each technique, will be discussed.

Cannabis use in people with Parkinson's disease and Multiple Sclerosis: A web-based investigation.

OBJECTIVES: Cannabis has been used for medicinal purpose for thousands of years; however the positive and negative effects of cannabis use in Parkinson's disease (PD) and Multiple Sclerosis (MS) are mostly unknown. Our aim was to assess cannabis use in PD and MS and compare results of self-reported assessments of neurological disability between current cannabis users and non-users. METHODS: An anonymous web-based survey was hosted on the Michael J. Fox Foundation and the National Multiple Sclerosis Society webpages from 15 February to 15 October 2016. The survey collected demographic and cannabis use information, and used standardized questionnaires to assess neurological function, fatigue, balance, and physical activity participation. Analysis of variance and chi-square tests were used for the analysis. RESULTS: The survey was viewed 801 times, and 595 participants were in the final data set. Seventy-six percent and 24% of the respondents reported PD and MS respectively. Current users reported high efficacy of cannabis, 6.4 (SD 1.8) on a scale from 0 to 7 and 59% reported reducing prescription medication since beginning cannabis use. Current cannabis users were younger and less likely to be classified as obese (P < 0.035). Cannabis users reported lower levels of disability, specifically in domains of mood, memory, and fatigue (P<0.040). CONCLUSIONS: Cannabis may have positive impacts on mood, memory, fatigue, and obesity status in people with PD and MS. Further studies using clinically and longitudinally assessed measurements of these domains are needed to establish if these associations are causal and determine the long-term benefits and consequences of cannabis use in people with PD and MS.

Fatigue in Multiple Sclerosis: Misconceptions and Future Research Directions.

Fatigue is one of the most disabling side effects in people with multiple sclerosis. While this fact is well known, there has been a remarkable lack of progress in determining the pathophysiological mechanisms behind fatigue and the establishment of effective treatments. The main barrier has been the lack of a unified definition of fatigue that can be objectively tested with validated experimental models. In this "perspective article" we propose the use of the following model and definition of fatigue: the decrease in physical and/or mental performance that results from changes in central, psychological, and/or peripheral factors. These changes depend on the task being performed, the environmental conditions it is performed in, and the physical and mental capacity of the individual. Our definition and model of fatigue outlines specific causes of fatigue and how it affects task performance. We also outline the strengths and weaknesses of commonly used measures of fatigue and suggest, based on our model and definition, new research strategies, which should include multiple measures. These studies should be mechanistic with validated experimental models to determine changes in central, psychological, and/or peripheral factors that explain fatigue. The proposed new research strategies may lead to the identification of the origins of MS related fatigue and the development of new, more effective treatments.

FDG-PET detects nonuniform muscle activity in the lower body during human gait.

INTRODUCTION: Nonuniform muscle activity has been partially explained by anatomically defined neuromuscular compartments. The purpose of this study was to investigate the uniformity of skeletal muscle activity during walking. METHODS: Eight participants walked at a self-selected speed, and muscle activity was quantified using [18 F]-fluorodeoxyglucose positron emission tomography imaging. Seventeen muscles were divided into 10 equal length sections, and within muscle activity was compared. RESULTS: Nonuniform activity was detected in 12 of 17 muscles (ƒ > 4.074; P < 0.046), which included both uni- and multi-articular muscles. Greater proximal activity was detected in 6 muscles (P < 0.049), and greater distal versus medial activity was found in the iliopsoas (P < 0.042). CONCLUSIONS: Nonuniform muscle activity is likely related to recruitment of motor units located within separate neuromuscular compartments. These findings indicate that neuromuscular compartments are recruited selectively to allow for efficient energy transfer, and these patterns may be task-dependent. Muscle Nerve 54: 959-966, 2016.

Brown adipose and central nervous system glucose uptake is lower during cold exposure in older compared to young men: a preliminary PET study.

The purpose of this study was to determine the activity of brown adipose tissue (BAT) and the central nervous system (CNS) during cold exposure in young and older men. Two young, 24 and 21 years, and two older, 76 and 74 years, men participated in the study. Positron emission tomography images showed cold-induced BAT activity was absent in older men but clearly present in the clavicular region of the young men (Standardized Uptake Value: SUVmean: 3.12 and 3.71). Statistical parametric mapping revealed cortical brain activity was lower in the older men within areas of the frontal, parietal, temporal, and occipital lobes, and the thalamus (peak-level p uncorr  < 0.036). Cervical spinal cord SUVmean values tended to be lower for older (SUVmean: 1.64 and 1.61) compared to young men (SUVmean: 1.91 and 1.71). These preliminary findings suggest lower BAT activity in older men may in part be due to lower CNS activity.

Cognitive-Motor Related Brain Activity During Walking: Differences Between Men and Women With Multiple Sclerosis.

OBJECTIVE: To determine if sex differences in glucose uptake, a marker of brain activity, are present in brain regions that facilitate walking performance in persons with multiple sclerosis (MS). DESIGN: Cross-sectional, observational pilot. SETTING: University laboratory. PARTICIPANTS: Positron emission tomography with fluorine-18-labeled deoxyglucose (FDG) was performed on persons with MS and healthy controls (4 men and 4 women per group; N=16) after a 15-minute walking test. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURE: Brain activity was quantified as the mean standardized uptake value (SUV). RESULTS: The mean SUV was significantly lower in the thalamus (P=.029) and cerebellum (P=.029) for men with MS compared with women with MS, but not for the prefrontal (P=.057) or frontal (P=.057) cortices. Similar nonsignificant trends were found for healthy controls. No mean SUV group × sex interaction effects were found between the MS and healthy control groups (all P>.05). CONCLUSIONS: To our knowledge, this is the first study of brain activity sex differences based on FDG uptake in persons with MS during walking. Significantly less FDG uptake in the thalamus and cerebellum brain regions important for walking performance was found in men with MS compared with women with MS; however, these comparisons were not significantly different in the healthy control group. No differences in FDG uptake were found between the MS and healthy control groups in any of the brain regions examined. Results from this study provide pilot data for larger studies aimed at identifying underlying mechanisms responsible for accelerated disability in men with MS.

Core muscle characteristics during walking of patients with multiple sclerosis.

The purpose of this study was to investigate core muscle characteristics during walking in patients with multiple sclerosis (MS). Eight patients (4 men) with relapsing-remitting MS (aged 44.9 +/- 8.6 yr) and sex-matched controls (37.9 +/- 8.4 yr) walked on a treadmill for 15 min at a self-selected speed. Positron emission tomography/computed tomography imaging was used to measure core muscle activity immediately after walking based on glucose uptake. Activity was not different between the MS and control group for any of the identified muscles (p > 0.28). Within the MS group, side differences in activity were identified in the lateral flexor group, the external and internal obliques, and the rectus abdominis (p < 0.05), with the less-affected side being activated more. Furthermore, greater muscle volume was found on the more-affected side of the transversus abdominis, quadratus lumborum, and the low-back extensor group (p < 0.03). These muscle characteristics suggest patients with MS utilize compensatory mechanisms during walking to maintain balance and posture. These strategies likely result in increased muscle energy cost and early fatigability.

Walking Speed and Brain Glucose Uptake are Uncoupled in Patients with Multiple Sclerosis.

Motor impairments of the upper and lower extremities are common symptoms of multiple sclerosis (MS). While some peripheral effects like muscle weakness and loss of balance have been shown to influence these symptoms, central nervous system activity has not been fully elucidated. The purpose of this study was to determine if alterations in glucose uptake were associated with motor impairments in patients with multiple sclerosis. Eight patients with multiple sclerosis (four men) and eight sex matched healthy controls performed 15 min of treadmill walking at a self-selected pace, during which ≈322 MBq of the positron emission tomography (PET) glucose analog [(18)F]-fluorodeoxyglucose (FDG) was injected. Immediately after the cessation of walking, participants underwent PET imaging. Patients with MS had lower FDG uptake in ≈40% of the brain compared to the healthy controls (p FWE-corr < 0.001, q FDR-corr < 0.001, k e = 93851) and walked at a slower speed [MS, 1.1 (0.2), controls 1.4 (0.1), m/s, P = 0.014]. Within the area of lower FDG uptake 15 regions were identified. Of these 15 regions, 13 were found to have strong to moderate correlations to walking speed within the healthy controls (r > -0.75, P < 0.032). Within patients with MS only 3 of the 15 regions showed significant correlations: insula (r = -0.74, P = 0.036), hippocampus (r = -0.72, P = 0.045), and calcarine sulcus (r = -0.77, P = 0.026). This data suggest that walking impairments in patients with MS may be due to network wide alterations in glucose metabolism. Understanding how brain activity and metabolism are altered in patients with MS may allow for better measures of disability and disease status within this clinical population.

Regional differences of [(18)F]-FDG uptake within the brain during fatiguing muscle contractions.

BACKGROUND AND PURPOSE: Many studies have shown that a position task is more difficult than a force task although both are performed at a similar net muscle force. Thus, the time to task failure is consistently shown to be briefer during the position task. The contributions of the central nervous system to these two types of fatiguing contractions are not completely understood. The purpose of this pilot study was to examine differences in regional brain activity between force and position tasks using positron emission tomography (PET) with [(18)F]-Fluorodeoxyglucose (FDG). METHODS: Two participants performed both a force and position task, separated by 7 days, with the elbow flexor muscles at 15% maximal voluntary contraction force. During both tasks, each participant was injected with ≈ 256 (SD 11) MBq of FDG. Immediately after both tasks PET imaging was performed and images were analyzed to determine FDG uptake within regions of the brain. RESULTS: FDG uptake was greater in the occipital and temporal cortices of the brain during the position task compared to the force task. CONCLUSIONS: These findings suggest that differences in visual-spatial feedback and processing may play a role in the reduced time to failure of position tasks. Future application of these findings may lead to improved designs of rehabilitative strategies involving different types of visual feedback.

[18F]-FDG positron emission tomography--an established clinical tool opening a new window into exercise physiology.

Positron emission tomography (PET) with [(18)F]-fluorodeoxyglucose (FDG) is an established clinical tool primarily used to diagnose and evaluate disease status in patients with cancer. PET imaging using FDG can be a highly valuable tool to investigate normal human physiology by providing a noninvasive, quantitative measure of glucose uptake into various cell types. Over the past years it has also been increasingly used in exercise physiology studies to identify changes in glucose uptake, metabolism, and muscle activity during different exercise modalities. Metabolically active cells transport FDG, an (18)fluorine-labeled glucose analog tracer, from the blood into the cells where it is then phosphorylated but not further metabolized. This metabolic trapping process forms the basis of this method's use during exercise. The tracer is given to a participant during an exercise task, and the actual PET imaging is performed immediately after the exercise. Provided the uptake period is of sufficient duration, and the imaging is performed shortly after the exercise; the captured image strongly reflects the metabolic activity of the cells used during the task. When combined with repeated blood sampling to determine tracer blood concentration over time, also known as the input function, glucose uptake rate of the tissues can be quantitatively calculated. This synthesis provides an accounting of studies using FDG-PET to measure acute exercise-induced skeletal muscle activity, describes the advantages and limitations of this imaging technique, and discusses its applications to the field of exercise physiology.

Glucose uptake heterogeneity of the leg muscles is similar between patients with multiple sclerosis and healthy controls during walking.

BACKGROUND: Difficulties in ambulation are one of the main problems reported by patients with multiple sclerosis. A previous study by our research group showed increased recruitment of muscle groups during walking, but the influence of skeletal muscle properties, such as muscle fiber activity, has not been fully elucidated. The purpose of this investigation was to use the novel method of calculating glucose uptake heterogeneity in the leg muscles of patients with multiple sclerosis and compare these results to healthy controls. METHODS: Eight patients with multiple sclerosis (4 men) and 8 healthy controls (4 men) performed 15 min of treadmill walking at a comfortable self-selected speed following muscle strength tests. Participants were injected with ≈ 8 mCi of [(18)F]-fluorodeoxyglucose during walking after which positron emission tomography/computed tomography imaging was performed. FINDINGS: No differences in muscle strength were detected between multiple sclerosis and control groups (P>0.27). Within the multiple sclerosis, group differences in muscle volume existed between the stronger and weaker legs in the vastus lateralis, semitendinosus, and semimembranosus (P<0.03). Glucose uptake heterogeneity between the groups was not different for any muscle group or individual muscle of the legs (P>0.16, P≥0.05). INTERPRETATIONS: Patients with multiple sclerosis and healthy controls showed similar muscle fiber activity during walking. Interpretations of these results, with respect to our previous study, suggest that walking difficulties in patients with multiple sclerosis may be more associated with altered central nervous system motor patterns rather than alterations in skeletal muscle properties.

Greater glucose uptake heterogeneity in knee muscles of old compared to young men during isometric contractions detected by [(18)F]-FDG PET/CT.

We used positron emission tomography/computed tomography (PET/CT) and [(18)F]-FDG to test the hypothesis that glucose uptake (GU) heterogeneity in skeletal muscles as a measure of heterogeneity in muscle activity is greater in old than young men when they perform isometric contractions. Six young (26 ± 6 years) and six old (77 ± 6 years) men performed two types of submaximal isometric contractions that required either force or position control. [(18)F]-FDG was injected during the task and PET/CT scans were performed immediately after the task. Within-muscle heterogeneity of knee muscles was determined by calculating the coefficient of variation (CV) of GU in PET image voxels within the muscles of interest. The average GU heterogeneity (mean ± SD) for knee extensors and flexors was greater for the old (35.3 ± 3.3%) than the young (28.6 ± 2.4%) (P = 0.006). Muscle volume of the knee extensors were greater for the young compared to the old men (1016 ± 163 vs. 598 ± 70 cm(3), P = 0.004). In a multiple regression model, knee extensor muscle volume was a predictor (partial r = -0.87; P = 0.001) of GU heterogeneity for old men (R (2) = 0.78; P < 0.001), and MVC force predicted GU heterogeneity for young men (partial r = -0.95, P < 0.001). The findings demonstrate that GU is more spatially variable for old than young men and especially so for old men who exhibit greater muscle atrophy.