Brain atrophy, reduced cerebral perfusion, arterial stiffening, and wall thickening with aging coincide with stimulus-specific changes in fMRI-BOLD responses.

The aim of this study was to investigate how aging affects blood flow and structure of the brain. It was hypothesized older individuals would have lower gray matter volume (GMV), resting cerebral blood flow (CBF0), and depressed responses to isometabolic and neurometabolic stimuli. In addition, increased carotid-femoral pulse-wave velocity (PWV), carotid intima-media thickness (IMT), and decreased brachial flow-mediated dilation (FMD) would be associated with lower CBF0, cerebrovascular reactivity (CVR), and GMV. Brain scans (magnetic resonance imaging) and cardiovascular examinations were conducted in young (age = 24 ± 3 yr, range = 22-28 yr; n = 13) and old (age = 71 ± 4 yr; range = 67-82 yr, n = 14) participants, and CBF0, CVR [isometabolic % blood oxygen level-dependent (BOLD) in response to a breath hold (BH)], brain activation patterns during a working memory task (neurometabolic %BOLD response to N-back trial), GMV, PWV, IMT, and FMD were measured. CBF0 and to a lesser extent CVRBH were lower in the old group (P ≤ 0.050); however, the increase in the %BOLD response to the memory task was not blunted (P ≥ 0.2867). Age-related differential activation patterns during the working memory task were characterized by disinhibition of the default mode network in the old group (P < 0.0001). Linear regression analyses revealed PWV, and IMT were negatively correlated with CBF0, CVRBH, and GMV across age groups, but within the old group alone only the relationships between PWV-CVRBH and IMT-GMV remained significant (P ≤ 0.0183). These findings suggest the impacts of age on cerebral %BOLD responses are stimulus specific, brain aging involves alterations in cerebrovascular and possibly neurocognitive control, and arterial stiffening and wall thickening may serve a role in cerebrovascular aging.NEW & NOTEWORTHY Cerebral perfusion was lower in old versus young adults. %Blood oxygen level-dependent (BOLD) responses to an isometabolic stimulus and gray matter volume were decreased in old versus young adults and associated with arterial stiffening and wall thickening. The increased %BOLD response to a neurometabolic stimulus appeared unaffected by age; however, the old group displayed disinhibition of the default mode network during the stimulus. Thus, age-related alterations in cerebral %BOLD responses were stimulus specific and related to arterial remodeling.

Acute changes in forearm vascular compliance during transient sympatho-excitation.

The study of vascular regulation often omits important information about the elastic properties of arteries under conditions of pulsatile flow. The purpose of this study was to examine the relationship between muscle sympathetic nerve activity (MSNA), vascular bed compliance, and peripheral blood flow responses in humans. We hypothesized that increases in MSNA would correlate with reductions in vascular compliance, and that changes in compliance would correspond with changes in peripheral blood flow during sympatho-excitation. MSNA (microneurography), blood pressure (Finopres), and brachial artery blood flow (Doppler ultrasound), were monitored in six healthy males at baseline and during the last 15 s of voluntary end-inspiratory, expiratory apneas and 5 min of static handgrip exercise (SHG; 20% maximum voluntary contraction) and 3 min of post-exercise circulatory occlusion (SHG + PECO; measured in the non-exercising arm). A lumped Windkessel model was employed to examine vascular bed compliance. During apnea, indices of MSNA were inversely related with vascular compliance, and reductions in compliance correlated with decreased brachial blood flow rate. During SHG, despite increased MSNA, compliance also increased, but was unrelated to increases in blood flow. Neither during SHG nor PECO did indices of MSNA correlate with forearm vascular compliance nor did vascular compliance correlate with brachial flow. However, during PECO, a linear combination of blood pressure and total MSNA was correlated with vascular compliance. These data indicate the elastic components of the forearm vasculature are regulated by adrenergic and myogenic mechanisms during sympatho-excitation, but in a reflex-dependent manner.

Cerebral haemodynamics during arrhythmia in health, ischaemic heart disease and heart failure with reduced ejection fraction, and in a preclinical swine model.

Ventricular arrhythmias are associated with neurological impairment and could represent a source of cerebral hypoperfusion. In the present study, data from healthy individuals (n = 11), patients with ischaemic heart disease (IHD; ejection fraction >40%; n = 9) and patients with heart failure with reduced ejection fraction (HFrEF; EF = 31 (5)%, n = 11), as well as data from swine surgeries, where spontaneous ventricular arrhythmias were observed during cerebrovascular examination (transcranial Doppler ultrasound in humans and laser Doppler in swine) were analysed retrospectively to investigate the effect of arrhythmia on cerebral microvascular haemodynamics. A subset of participants also completed the Montreal Cognitive Assessment (MoCA). Middle cerebral artery mean blood velocity (MCAVmean ) decreased during premature ventricular contraction (PVC) in all groups, and data from swine indicate PVCs reduced cerebral microvascular perfusion. Overall MCAVmean was decreased in the HFrEF vs. control group. Further, %∆MCAVmean /%∆mean arterial pressure during the PVC was greater in the HFrEF vs. control group and was correlated with decreased MoCA scores. Subanalysis of HFrEF data revealed that during bigeminy MCAVmean decreased owing to reductions during irregular beats only. During non-sustained ventricular tachycardia, MCAVmean decreased but recovered above baseline upon return to sinus rhythm. Also, haemodynamic perturbations during and following the PVC were greater in the brachial artery vs. the MCA. Therefore, ventricular arrhythmias decreased indices of cerebral perfusion irrespective of IHD or HFrEF. The relative magnitude of arrhythmia-induced haemodynamic perturbations appears to be population specific and arrhythmia type and organ dependent. The cumulative burden of arrhythmia-induced deficits may exacerbate existing cerebral hypoperfusion in HFrEF and contribute to neurological abnormalities in this population. KEY POINTS: Irregular heartbeats are often considered benign in isolation, but individuals who experience them frequently have a higher prevalence of cerebrovascular and/or cognitive associated disorders. How irregular heartbeats affect blood pressure and cerebral haemodynamics in healthy and cardiovascular disease patients, those with and without reduced ejection fraction, remains unknown. Here it was found that in the absence of symptoms associated with irregular heartbeats, such as dizziness or hypotension, single, multiple non-sustained and sustained irregular heartbeats influence cerebral haemodynamics in a population-specific, arrhythmia-type and organ-dependent manner. Relative deficits in the index of cerebral blood flow normalized to relative deficits in blood pressure were greatest in patients with heart failure with reduced ejection and inversely related with cognitive performance. Chronic arrhythmias may exacerbate existing cerebral hypoperfusion in heart failure with reduced ejection fraction, thereby providing a mechanistic link between otherwise benign irregular heartbeats and cognitive dysfunction, independent of embolism.

The physiological basis underlying functional connectivity differences in older adults: A multi-modal analysis of resting-state fMRI.

The purpose of this study was to determine if differences in functional connectivity strength (FCS) with age were confounded by vascular parameters including resting cerebral blood flow (CBF0), cerebrovascular reactivity (CVR), and BOLD-CBF coupling. Neuroimaging data were collected from 13 younger adults (24 ± 2 years) and 14 older adults (71 ± 4 years). A dual-echo resting state pseudo-continuous arterial spin labeling sequence was performed, as well as a BOLD breath-hold protocol. A group independent component analysis was used to identify networks, which were amalgamated into a region of interest (ROI). Within the ROI, FC strength (FCS) was computed for all voxels and compared across the groups. CBF0, CVR and BOLD-CBF coupling were examined within voxels where FCS was different between young and older adults. FCS was greater in old compared to young (P = 0.001). When the effect of CBF0, CVR and BOLD-CBF coupling on FCS was examined, BOLD-CBF coupling had a significant effect (P = 0.003) and group differences in FCS were not present once all vascular parameters were considered in the statistical model (P = 0.07). These findings indicate that future studies of FCS should consider vascular physiological markers in order to improve our understanding of aging processes on brain connectivity.

Neuroprotective effects of exercise on the aging human neuromuscular system.

Human biological aging from maturity to senescence is associated with a gradual loss of muscle mass and neuromuscular function. It is not until very old age (>80 years) however, that these changes often manifest into functional impairments. A driving factor underlying the age-related loss of muscle mass and function is the reduction in the number and quality of motor units (MUs). A MU consists of a single motoneuron, located either in the spinal cord or the brain stem, and all of the muscle fibres it innervates via its peripheral axon. Throughout the adult lifespan, MUs are slowly, but progressively lost. The compensatory process of collateral reinnervation attempts to recapture orphaned muscle fibres following the death of a motoneuron. Whereas this process helps mitigate loss of muscle mass during the latter decades of adult aging, the neuromuscular system has fewer and larger MUs, which have lower quality connections between the axon terminal and innervated muscle fibres. Whether this process of MU death and degradation can be attenuated with habitual physical activity has been a challenging question of great interest. This review focuses on age-related alterations of the human neuromuscular system, with an emphasis on the MU, and presents findings on the potential protective effects of lifelong physical activity. Although there is some discrepancy across studies of masters athletes, if one considers all experimental limitations as well as the available literature in animals, there is compelling evidence of a protective effect of chronic physical training on human MUs. Our tenet is that high-levels of physical activity can mitigate the natural trajectory of loss of quantity and quality of MUs in old age.

Cerebrovascular insufficiency and amyloidogenic signaling in Ossabaw swine with cardiometabolic heart failure.

Individuals with heart failure (HF) frequently present with comorbidities, including obesity, insulin resistance, hypertension, and dyslipidemia. Many patients with HF experience cardiogenic dementia, yet the pathophysiology of this disease remains poorly understood. Using a swine model of cardiometabolic HF (Western diet+aortic banding; WD-AB), we tested the hypothesis that WD-AB would promote a multidementia phenotype involving cerebrovascular dysfunction alongside evidence of Alzheimer's disease (AD) pathology. The results provide evidence of cerebrovascular insufficiency coupled with neuroinflammation and amyloidosis in swine with experimental cardiometabolic HF. Although cardiac ejection fraction was normal, indices of arterial compliance and cerebral blood flow were reduced, and cerebrovascular regulation was impaired in the WD-AB group. Cerebrovascular dysfunction occurred concomitantly with increased MAPK signaling and amyloidogenic processing (i.e., increased APP, BACE1, CTF, and Aß40 in the prefrontal cortex and hippocampus) in the WD-AB group. Transcriptomic profiles of the stellate ganglia revealed the WD-AB group displayed an enrichment of gene networks associated with MAPK/ERK signaling, AD, frontotemporal dementia, and a number of behavioral phenotypes implicated in cognitive impairment. These provide potentially novel evidence from a swine model that cerebrovascular and neuronal pathologies likely both contribute to the dementia profile in a setting of cardiometabolic HF.

Pathophysiology and management of critical illness polyneuropathy and myopathy.

Critical illness-associated weakness (CIAW) is an umbrella term used to describe a group of neuromuscular disorders caused by severe illness. It can be subdivided into three major classifications based on the component of the neuromuscular system (i.e. peripheral nerves or skeletal muscle or both) that are affected. This includes critical illness polyneuropathy (CIP), critical illness myopathy (CIM), and an overlap syndrome, critical illness polyneuromyopathy (CIPNM). It is a common complication observed in people with critical illness requiring intensive care unit (ICU) admission. Given CIAW is found in individuals experiencing grave illness, it can be challenging to study from a practical standpoint. However, over the past 2 decades, many insights into the pathophysiology of this condition have been made. Results from studies in both humans and animal models have found that a profound systemic inflammatory response and factors related to bioenergetic failure as well as microvascular, metabolic, and electrophysiological alterations underlie the development of CIAW. Current management strategies focus on early mobilization, achieving euglycemia, and nutritional optimization. Other interventions lack sufficient evidence, mainly due to a dearth of large trials. The goal of this Physiology in Medicine article is to highlight important aspects of the pathophysiology of these enigmatic conditions. It is hoped that improved understanding of the mechanisms underlying these disorders will lead to further study and new investigations for novel pharmacologic, nutritional, and exercise-based interventions to optimize patient outcomes.

Effect of Acute High-intensity Interval Exercise on Whole-body Fat Oxidation and Subcutaneous Adipose Tissue Cell Signaling in Overweight Women.

Exercise-induced alterations in adipose tissue insulin and/or ß-adrenergic signaling may contribute to increases in whole-body fat oxidation following acute exercise. Thus, we examined changes in insulin (Akt, AS160) and ß-adrenergic (PKA) signaling proteins in subcutaneous adipose tissue and whole-body fat oxidation in overweight women following acute high-intensity interval exercise (HIIE). Overweight females completed two experimental sessions in a randomized order: 1) control (bed rest) and 2) HIIE (10 × 4 min running intervals at 90% HRmax, 2-min recovery). Subcutaneous abdominal adipose tissue biopsies were obtained from 10 participants before (pre-), immediately (0hr) after (post-), 2hr post-, and 4hr post-exercise. Plasma glucose and insulin levels were assessed in venous blood samples obtained at each biopsy time-point from a different group of 5 participants (BMI-matched to biopsy group). Fat oxidation rates were estimated using the respiratory exchange ratio (RER) in all participants using indirect calorimetry pre-, 2hr post-, and 4hr post-exercise. RER was decreased (p < 0.05) at 2hr post-exercise after HIIE (0.77 ± 0.04) compared to control (0.84 ± 0.04). Despite higher plasma glucose (p < 0.01) and insulin (p < 0.05) levels at 0hr post-exercise versus control, no significant interaction effects were observed for Akt or AS160 phosphorylation (p > 0.05). Phosphorylation of PKA substrates was unaltered in both conditions (p > 0.05). Collectively, altered ß-adrenergic and insulin signaling in subcutaneous adnominal adipose tissue does not appear to explain increased whole-body fat oxidation following acute HIIE.

Maintaining Motor Units into Old Age: Running the Final Common Pathway.

Invited Letter to the Editor. This article is a commentary on the recently published manuscript "Use it or lose it: tonic activity of slow motoneurons promotes their survival and preferentially increases slow fiber-type groupings in muscles of old lifelong recreational sportsmen". Mosole S, Carraro U, Kern H, Loefler S, Zampieri S. Use it or lose it: tonic activity of slow motoneurons promotes their survival and preferentially increases slow fiber-type groupings in muscles of old lifelong recreational sportsmen. Eur J Transl Myol 2016;26:5972. doi: 10.4081/ejtm.2016.5972. We offer some unique perspectives on masters athletes and the role of physical activity in maintaining the number and function of motor units into old age.

Electrophysiological and neuromuscular stability of persons with chronic inflammatory demyelinating polyneuropathy.

INTRODUCTION: We assessed motor unit (MU) properties and neuromuscular stability in the tibialis anterior (TA) of chronic inflammatory demyelinating polyneuropathy (CIDP) patients using decomposition-based quantitative electromyography. METHODS: Dorsiflexion strength was assessed, and surface and concentric needle electromyography were sampled from the TA. Estimates of MU numbers were derived using decomposition-based quantitative electromyography and spike-triggered averaging. Neuromuscular transmission stability was assessed from concentric needle-detected MU potentials. RESULTS: CIDP patients had 43% lower compound muscle action potential amplitude than controls, and despite near-maximum voluntary activation, were 37% weaker. CIDP had 27% fewer functioning MUs in the TA, and had 90% and 44% higher jiggle and jitter values, respectively compared with controls. CONCLUSIONS: CIDP had lower strength and compound muscle action potential values, moderately fewer numbers of MUs, and significant neuromuscular instability compared with controls. Thus, in addition to muscle atrophy, voluntary weakness is also due to limitations of peripheral neural transmission consistent with demyelination. Muscle Nerve 56: 413-420, 2017.

Motor unit number and transmission stability in octogenarian world class athletes: Can age-related deficits be outrun?

Our group has shown a greater number of functioning motor units (MU) in a cohort of highly active older (∼65 yr) masters runners relative to age-matched controls. Because of the precipitous loss in the number of functioning MUs in the eighth and ninth decades of life it is unknown whether older world class octogenarian masters athletes (MA) would also have greater numbers of functioning MUs compared with age-matched controls. We measured MU numbers and neuromuscular transmission stability in the tibialis anterior of world champion MAs (∼80 yr) and compared the values with healthy age-matched controls (∼80 yr). Decomposition-enhanced spike-triggered averaging was used to collect surface and intramuscular electromyography signals during dorsiflexion at ∼25% of maximum voluntary isometric contraction. Near fiber (NF) MU potential analysis was used to assess neuromuscular transmission stability. For the MAs compared with age-matched controls, the amount of excitable muscle mass (compound muscle action potential) was 14% greater (P < 0.05), there was a trend (P = 0.07) toward a 27% smaller surface-detected MU potential representative of less collateral reinnervation, and 28% more functioning MUs (P < 0.05). Additionally, the MAs had greater MU neuromuscular stability than the controls, as indicated by lower NF jitter and jiggle values (P < 0.05). These results demonstrate that high-performing octogenarians better maintain neuromuscular stability of the MU and mitigate the loss of MUs associated with aging well into the later decades of life during which time the loss of muscle mass and strength becomes functionally relevant. Future studies may identify the concomitant roles genetics and exercise play in neuroprotection.

Physiology in Medicine: neuromuscular consequences of diabetic neuropathy.

Diabetic polyneuropathy (DPN) refers to peripheral nerve dysfunction as a complication of diabetes mellitus. This condition is relatively common and is likely a result of vascular and/or metabolic disturbances related to diabetes. In the early or less severe stages of DPN it typically results in sensory impairments but can eventually lead to major dysfunction of the neuromuscular system. Some of these impairments may include muscle atrophy and weakness, slowing of muscle contraction, and loss of power and endurance. Combined with sensory deficits these changes in the motor system can contribute to decreased functional capacity, impaired mobility, altered gait, and increased fall risk. There is no pharmacological disease-modifying therapy available for DPN and the mainstay of treatment is linked to treating the diabetes itself and revolves around strict glycemic control. Exercise therapy (including aerobic, strength, or balance training-based exercise) appears to be a promising preventative and treatment strategy for patients with DPN and those at risk. The goal of this Physiology in Medicine article is to highlight important and overlooked dysfunction of the neuromuscular system as a result of DPN with an emphasis on the physiologic basis for that dysfunction. Additionally, we sought to provide information that clinicians can use when following patients with diabetes or DPN including support for the inclusion of exercise-based therapy as an effective, accessible, and inexpensive form of treatment.

Reduced skeletal muscle quantity and quality in patients with diabetic polyneuropathy assessed by magnetic resonance imaging.

INTRODUCTION: The aim of this study was to determine whether diabetic polyneuropathy (DPN) is associated with reduced muscle quality using MRI. METHODS: MRIs of the tibialis anterior (TA) muscle were recorded from 9 individuals (5 men) with DPN (∼65 years) and 8 (4 men) age- and gender-matched controls. A magnetization transfer ratio (MTR) and T2 relaxation times of the TA were calculated. RESULTS: Despite equal voluntary activation, the DPN group was ∼37% weaker than controls, with a significantly lower proportion (∼8%) of contractile tissue and lower MTR (0.28 ± 0.03 vs. 0.32 ± 0.02 percent units). T2 relaxation time was significantly longer in the DPN group (77 ± 16 ms) compared with controls (63 ± 6 ms). CONCLUSIONS: These findings indicate a reduction in the structural integrity and myocellular protein density in the TA of those with DPN. Thus, muscle weakness in DPN is likely due to both a loss of muscle mass and a reduction in contractile quality.

Blood flow and muscle oxygenation during low, moderate, and maximal sustained isometric contractions.

A reduction of blood flow to active muscle will precipitate fatigue, and sustained isometric contractions produce intramuscular and compartmental pressures that can limit flow. The present study explored how blood flow and muscle oxygenation respond to isometric contractions at low, moderate, and maximal intensities. Over two visits, 10 males (26 ± 2 yr; means ± SD) performed 1-min dorsiflexion contractions at 30, 60, and 100% of maximal voluntary contraction (MVC) torque. Doppler ultrasound of the anterior tibial artery was used to record arterial diameter and mean blood velocity and to calculate absolute blood flow. The tissue oxygenation index (TOI) of tibialis anterior was acquired with near-infrared spectroscopy (NIRS). There was a progressive increase in blood flow at 30% MVC (peak of 289 ± 139% resting value), no change from rest until an increase in the final 10 s of exercise at 60% MVC (peak of 197 ± 102% rest), and an initial decrease (59 ± 30% resting value) followed by a progressive increase at 100% MVC (peak of 355 ± 133% rest). Blood flow was greater at 30 and 100% than 60% MVC during the last 30 s of exercise. TOI was ∼63% at rest and, within 30 s of exercise, reached steady-state values of ∼42%, ∼22%, and ∼22% for 30, 60, and 100% MVC, respectively. Even maximal contraction of the dorsiflexors is unable to cause more than a transient decrease of flow in the anterior tibial artery. Unlike dynamic or intermittent isometric exercise, our results indicate blood flow is not linearly graded with intensity or directly coupled with oxygenation during sustained isometric contractions.

Decreased muscle endurance associated with diabetic neuropathy may be attributed partially to neuromuscular transmission failure.

Diabetic polyneuropathy (DPN) can cause muscle atrophy, weakness, contractile slowing, and neuromuscular transmission instability. Our objective was to assess the response of the impaired neuromuscular system of DPN in humans when stressed with a sustained maximal voluntary contraction (MVC). Baseline MVC and evoked dorsiflexor contractile properties were assessed in DPN patients (n = 10) and controls (n = 10). Surface electromyography was used to record tibialis anterior evoked maximal compound muscle action potentials (CMAPs) and neuromuscular activity during MVCs. Participants performed a sustained isometric dorsiflexion MVC for which task termination was determined by the inability to sustain ≥60% MVC torque. The fatigue protocol was immediately followed by a maximal twitch, with additional maximal twitches and MVCs assessed at 30 s and 2 min postfatigue. DPN patients fatigued ∼21% more quickly than controls (P < 0.05) and featured less relative electromyographic activity during the first one-third of the fatigue protocol compared with controls (P < 0.05). Immediately following fatigue, maximal twitch torque was reduced similarly (∼20%) in both groups, and concurrently CMAPs were reduced (∼12%) in DPN patients, whereas they were unaffected in controls (P > 0.05). Twitch torque and CMAP amplitude recovered to baseline 30 s postfatigue. Additionally, at 30 s postfatigue, both groups had similar (∼10%) reductions in MVC torque relative to baseline, and MVC strength recovered by 2 min postfatigue. We conclude DPN patients possess less endurance than controls, and neuromuscular transmission failure may contribute to this greater fatigability.

Increased neuromuscular transmission instability and motor unit remodelling with diabetic neuropathy as assessed using novel near fibre motor unit potential parameters.

OBJECTIVE: To assess the degree of neuromuscular transmission variability and motor unit (MU) remodelling in patients with diabetic polyneuropathy (DPN) using decomposition-based quantitative electromyography (DQEMG) and near fibre (NF) motor unit potential (MUP) parameters. METHODS: The tibialis anterior (TA) muscle was tested in 12 patients with DPN (65 ± 15 years) and 12 controls (63 ± 15 years). DQEMG was used to analyze electromyographic (EMG) signals collected during voluntary contractions. MUP and NF MUP parameters were analyzed. NF MUPs were obtained by high-pass filtering MUP template waveforms, which isolates contributions of fibres that are close to the needle detection surface. NF MUP parameters provided assessment of motor unit size (NF area), fibre density (NF fibre count) and contribution dispersion (NF dispersion) and neuromuscular transmission instability (NF jiggle). RESULTS: DPN patients had larger (+45% NF area), more complex (+30% NF fibre count), and less stable (+30% NF jiggle) NF MUPs (p<0.05). No significant relationships were found between NF MUP stability and denervation, or strength; however NF MUP complexity was positively related to TA denervation in the DPN group (r=0.63; p<0.05). NF MUP complexity and instability were positively related in DPN patients (r=0.46; p<0.05). CONCLUSIONS: DPN is associated with neuromuscular transmission instability and MU remodelling that can be assessed using DQEMG. SIGNIFICANCE: DQEMG-derived NF MUP parameters may be useful in identifying patients in early stages of neuromuscular dysfunction related to DPN.

The altered vestibular-evoked myogenic and whole-body postural responses in old men during standing.

Age-related decrements within the sensorimotor system may lead to alterations and impairments in postural control, but a link to a vestibular mechanism is unclear. The purpose of the present study was to determine whether vestibular control of standing balance is altered with adult aging. Eight old (~77 years) and eight young (~26 years) men stood without aids on a commercially available force plate with their head turned to the right, arms relaxed at their sides and eyes closed while receiving stochastic vestibular stimuli (0-25 Hz, root mean square amplitude=0.85 mA). Surface electromyography signals were sampled from the left soleus, medial gastrocnemius and tibialis anterior. Whole-body balance, as measured by the anteroposterior forces and muscle responses, was quantified using frequency (coherence and gain functions) and time (cumulant density function) domain correlations with the vestibular stimuli. Old men exhibited a compressed frequency response of the vestibular reflex with a greater relative gain at lower frequencies for the plantar flexors and anteroposterior forces than young. In the time domain, the peak amplitude of the short latency response was 45-64% lower for the plantar flexors and anteroposterior forces (p≤0.05) in the old than young, but not for the tibialis anterior (p=0.21). The old men had a 190% and 31% larger medium latency response for only the tibialis anterior and anteroposterior forces, respectively, than young (p≤0.01). A strong correlation between the tibialis anterior and the force response was also detected (r=0.80, p<0.01). In conclusion, net vestibular-evoked muscle responses led to smaller short and larger medium latency peak amplitudes in anteroposterior forces for the old. The present results likely resulted from a compressed and lower operational frequency range of the vestibular reflexes and the activation of additional muscles (tibialis anterior) to maintain standing balance.