Matti D. Allen

Motor unit loss and weakness in association with diabetic neuropathy in humans.

Diabetes mellitus can be associated with peripheral neuropathy which may affect numbers of functioning motor units (MUs) of limb muscles. Direct quantitative assessment of MU numbers and muscle strength have not been performed in humans. We compared the estimated number of MUs of individuals with diabetic polyneuropathy (DPN) versus controls.

Skeletal muscle morphology and contractile function in relation to muscle denervation in diabetic neuropathy

The objective of the study was to assess the effects of diabetic polyneuropathy (DPN) on muscle contractile properties in humans, and how these changes are related to alterations in muscle morphology and denervation. Patients with DPN (n = 12) were compared with age- and sex-matched controls (n = 12). Evoked and voluntary contractile properties, including stimulated twitch responses and maximal voluntary contractions, of the dorsiflexor muscles were assessed using an isometric ankle dynamometer. Motor unit number estimates (MUNE) of the tibialis anterior (TA) were performed via quantitative electromyography and decomposition-enhanced spike-triggered averaging. Peak tibialis anterior (TA) cross-sectional area (CSA; cm(2)), and relative proportion of contractile to noncontractile tissue (%) was determined from magnetic resonance images. Patients with DPN demonstrated decreased strength (-35%) and slower (-45%) dorsiflexion contractile properties for both evoked and voluntary contractions (P < 0.05). These findings were not accounted for by differences in voluntary activation (P > 0.05) or antagonist coactivation (P > 0.05). Additionally, patients with DPN were weaker when strength was normalized to TA total CSA (-30%; P < 0.05) or contractile tissue CSA (-26%; P < 0.05). In the DPN patient group, TA MUNEs were negatively related to both % noncontractile tissue (P < 0.05; r = 0.72) and twitch half-relaxation time (P < 0.05; r = 0.60), whereas no relationships were found between these variables in controls (P > 0.05). We conclude that patients with DPN demonstrated reduced strength and muscle quality as well as contractile slowing. This process may contribute to muscle power loss and functional impairments reported in patients with DPN, beyond the loss of strength commonly observed.

The effect of knee joint angle on plantar flexor power in young and old men.

Human adult aging is associated with a loss of strength, contractile velocity and hence, power. The principal plantar flexors, consisting of the bi-articular gastrocnemeii and the mono-articular soleus, appear to be affected differently by the aging process. However, the age-related effect of knee joint angle on the torque-angular velocity relationship and power production of this functionally important muscle group is unknown. The purpose was to determine whether flexing the knee, thereby reducing the gastrocnemius contribution to plantar flexion, would exacerbate the age-related decrements in plantar flexion power, or shift the torque-angular velocity relationship differently in older compared with young men. Neuromuscular properties were recorded from 10 young (~25 y) and 10 old (~78 y) men with the knee extended (170°) and flexed (90°), in a randomized order. Participants performed maximal voluntary isometric contractions (MVCs), followed by maximal velocity-dependent shortening contractions at pre-set loads, ranging from 15 to 75% MVC. The young men were ~20-25% stronger, ~12% faster and ~30% more powerful than the old for both knee angles (P<0.05). In both age groups, isometric MVC torque was ~17% greater in the extended than flexed knee position, with no differences in voluntary activation (>95%). The young men produced 7-12% faster angular velocities in the extended knee position for loads ≤30% MVC, but no differences at higher loads; whereas there were no detectable differences in angular velocity between knee positions in the old across all relative loads. For both knee angles, young men produced peak power at 43.3±9.0% MVC, whereas the old men produced peak power at 54.8±7.9% MVC. These data indicate that the young, who have faster contracting muscles compared with the old, can rely more on velocity than torque for generating maximal power.

Length dependent loss of motor axons and altered motor unit properties in human diabetic polyneuropathy

OBJECTIVE To assess the number and properties of motor units in an upper and lower limb muscle (tibialis anterior [TA] and first dorsal interosseous [FDI]) in human diabetic polyneuropathy (DPN) using decomposition-based quantitative electromyography (DQEMG). METHODS DQEMG protocols were performed in the TA and FDI of 12 patients with confirmed diabetes mellitus and associated DPN, as well as 12 age-matched control participants. Maximal dorsiflexion strength was also assessed using a dynamometer. RESULTS In both muscles, patients with DPN had significantly reduced motor unit number estimates (MUNEs) (ΔTA ∼45%; ΔFDI ∼30%), compound muscle action potentials (CMAPs) (ΔTA ∼30%; ΔFDI ∼20%), and mean firing rates were reduced (ΔTA ∼15%; ΔFDI ∼15%) compared to controls (p<0.05). For the TA, patients with DPN had larger mean surface motor unit potentials (SMUPs) (ΔTA ∼40%; p<0.05), whereas in the FDI no differences were found (p>0.05). CONCLUSIONS DPN may result in motor unit loss, remodeling, and altered firing rate patterns. The magnitude of changes in the neuromuscular properties of DPN patients are muscle dependent and reflect a length-dependent disease progression. SIGNIFICANCE DQEMG may be a clinically useful technique in identifying the presence and severity of neuromuscular pathophysiology and tracking disease progression in DPN.

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.

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.

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.

Exercise training enhances insulin-stimulated nerve arterial vasodilation in rats with insulin-treated experimental diabetes

Insulin stimulates nerve arterial vasodilation through a nitric oxide (NO) synthase (NOS) mechanism. Experimental diabetes reduces vasa nervorum NO reactivity. Studies investigating hyperglycemia and nerve arterial vasodilation typically omit insulin treatment and use sedentary rats resulting in severe hyperglycemia. We tested the hypotheses that 1) insulin-treated experimental diabetes and inactivity (DS rats) will attenuate insulin-mediated nerve arterial vasodilation, and 2) deficits in vasodilation in DS rats will be overcome by concurrent exercise training (DX rats; 75-85% VO2 max, 1 h/day, 5 days/wk, for 10 wk). The baseline index of vascular conductance values (VCi = nerve blood flow velocity/mean arterial blood pressure) were similar (P ≥ 0.68), but peak VCi and the area under the curve (AUCi) for the VCi during a euglycemic hyperinsulinemic clamp (EHC; 10 mU·kg(-1)·min(-1)) were lower in DS rats versus control sedentary (CS) rats and DX rats (P ≤ 0.01). Motor nerve conduction velocity (MNCV) was lower in DS rats versus CS rats and DX rats (P ≤ 0.01). When compared with DS rats, DX rats expressed greater nerve endothelial NOS (eNOS) protein content (P = 0.04). In a separate analysis, we examined the impact of diabetes in exercise-trained rats alone. When compared with exercise-trained control rats (CX), DX rats had a lower AUCi during the EHC, lower MNCV values, and lower sciatic nerve eNOS protein content (P ≤ 0.03). Therefore, vasa nervorum and motor nerve function are impaired in DS rats. Such deficits in rats with diabetes can be overcome by concurrent exercise training. However, in exercise-trained rats (CX and DX groups), moderate hyperglycemia lowers vasa nervorum and nerve function.

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.

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.