Roger J. Paxton

Influence of Ascorbic Acid on the Thermic Effect of Feeding in Overweight and Obese Adult Humans

The thermic effect of feeding (TEF: increase in energy expenditure following acute energy intake) is an important physiological determinant of total daily energy expenditure and thus energy balance. Approximately 40% of TEF is believed to be mediated by sympathoadrenal activation and consequent β‐adrenergic receptor stimulation of metabolism. In sedentary adults, acute administration of ascorbic acid, a potent antioxidant, augments the thermogenic response to β‐adrenergic stimulation. We hypothesized that acute ascorbic acid administration augments TEF in sedentary overweight and obese adults. Energy expenditure was determined (ventilated hood technique) before and 4 h after consumption of a liquid‐mixed meal (caloric equivalent 40% of resting energy expenditure (REE)) in 11 sedentary, overweight/obese adults (5 men, 6 women; age: 24 ± 2 years; BMI: 28.5 ± 1.0 kg/m2 (mean ± s.e.)) on two separate, randomly ordered occasions: during continuous intravenous administration of saline (placebo control) and/or ascorbic acid (0.05 g/kg fat‐free mass). Acute ascorbic acid administration prevented the increase in plasma concentration of oxidized low‐density lipoprotein in the postprandial state (P = 0.04), but did not influence REE (1,668 ± 107 kcal/day vs.1,684 ± 84 kcal/day; P = 0.91) or the area under the TEF response curve (33.4 ± 2.4 kcal vs. 30.5 ± 3.6 kcal; P = 0.52) (control vs. ascorbic acid, respectively). Furthermore, acute ascorbic acid administration had no effect on respiratory exchange ratio, heart rate, or arterial blood pressure in the pre‐ and postabsorptive states (all P > 0.64). These data imply that the attenuated TEF commonly observed with sedentary lifestyle and obesity is not modulated by ascorbic acid‐sensitive oxidative stress.

Short-term sympathoadrenal inhibition augments the thermogenic response to β-adrenergic receptor stimulation

Sedentary behavior is associated with an attenuated thermogenic response to beta-adrenergic receptor (beta-AR) stimulation, an important regulator of energy expenditure (EE) in humans. Chronic stimulation of beta-ARs, via heightened activity of the sympathoadrenal system, leads to diminished beta-AR function. We have investigated the hypothesis that the thermogenic response of sedentary adults to beta-AR stimulation will be increased during short-term sympathoadrenal inhibition. Using a randomly ordered, repeated measures study design, resting EE (REE; indirect calorimetry, ventilated hood technique) and the % increase in EE above REE (%DeltaEE) during acute i.v. isoproterenol administration (nonselective beta-AR agonist; 6, 12, and 24 ng/kg fat-free mass per min) were determined in 16 sedentary adults (nine females and seven males, 25+/-1 years, body mass index: 26.1+/-0.9 kg/m(2), maximal oxygen uptake: 40+/-2 ml/kg per min (mean+/-s.e.m.)) in the basal state and on the 6th day of transdermal clonidine administration (centrally acting alpha2-AR agonist; 0.2 mg/day). Relative to baseline, clonidine inhibited sympathoadrenal activity, as evidenced by decreased plasma norepinephrine concentration (1.04+/-0.13 vs 0.34+/-0.03 nmol/l; P<0.001), skeletal muscle sympathetic nerve activity (22.5+/-3.8 vs 8.5+/-1.9 bursts/min; P=0.003), and resting heart rate (63+/-2 vs 49+/-1 beats/min; P<0.001). Sympathoadrenal inhibition decreased REE (6510+/-243 vs 5857+/-218 kJ/day; P<0.001), increased respiratory exchange ratio (0.84+/-0.01 vs 0.86+/-0.01; P=0.03), and augmented the thermogenic response to beta-AR stimulation (%DeltaEE: 11+/-2, 16+/-2, and 24+/-2 vs 14+/-1, 20+/-2, and 31+/-2; P=0.04). These data demonstrate that in sedentary humans, short-term inhibition of sympathoadrenal activity increases the thermogenic response to beta-AR stimulation, an important determinant of EE and hence energy balance.

Repeated sessions of functional repetitive transcranial magnetic stimulation increases motor cortex excitability and motor control in survivors of stroke.

OBJECTIVE To determine the impact of a single-session of repetitive transcranial magnetic stimulation (rTMS) and an rTMS intervention on neurophysiology and motor control in survivors of stroke. METHODS Twelve stroke survivors were randomized into functional-rTMS or passive-rTMS conditions. Measures of short-interval intracortical inhibition (SICI) and intracortical facilitation (ICF), and force steadiness (coefficient of variation, CV) at 10 and 20% of maximum voluntary contraction were assessed at baseline and after a single-session of rTMS (post single-session), and again following an intervention of 8 rTMS sessions (2 sessions per day; post-intervention). Functional-rTMS required subjects to exceed a muscle activation threshold assessed by surface electromyography to trigger each rTMS train; the passive-rTMS group received rTMS while relaxed. RESULTS ICF scores significantly increased following the single-session of functional-rTMS compared to the decrease following passive-rTMS. The increase in APB SICI and ICF scores following the intervention was significantly greater for the functional-rTMS group compared to the decreases following passive-rTMS. The groups were significantly different in the CV of force (20%) following the single-session of rTMS, and in the 10 and 20% tasks following the intervention. The functional-rTMS group increased steadiness overtime, whereas the passive group demonstrated a return to baseline following the intervention session. No differences were observed in first dorsal interosseus (FDI) measures (SICI and ICF) between groups. CONCLUSIONS The functional-rTMS protocol enhanced cortical excitability following a single-session and after repeated sessions and improved steadiness, whereas the passive stimulation protocol tended to decrease excitation and no improvements in steadiness were observed.

Acute Improvement in Intraoperative EMG Following Common Fibular Nerve Decompression in Patients with Symptomatic Diabetic Sensorimotor Peripheral Neuropathy: 1. EMG Results

Background and Study Aims Electromyographic (EMG) recordings of the fibularis longus (FL) and tibialis anterior (TA) muscles were performed intraoperatively during common fibular nerve (CFN) nerve decompression (ND) in patients with symptomatic diabetic sensorimotor peripheral neuropathy (DSPN) and clinical nerve compression. Materials and Methods Forty‐six legs in 40 patients underwent surgical ND by external neurolysis; FL and TA muscles were monitored intraoperatively. Evoked EMGs were recorded just prior to and within 1 minute after ND. Results Thirty‐eight legs (82.6%) demonstrated EMG improvement 1 minute after ND. Sixty muscles (31 FL, 29 TA) were monitored, with 44 (73.3%) improving in EMG amplitude. Mean change in EMG amplitude represented a 73.6% improvement (p < 0.0001). Changes in EMG amplitudes correlated with visual analog scale pain improvement (p = 0.03). Conclusion This is the first report of acute changes in objective EMG responses during ND of CFN in DSPN patients and demonstrates that patients with symptomatic DSPN and clinical nerve entrapment have latent but functional axons that surgical ND can improve immediately.

Visuomotor Correction is a Robust Contributor to Force Variability During Index Finger Abduction by Older Adults

We examined aging-related differences in the contribution of visuomotor correction to force fluctuations during index finger abduction via the analysis of two datasets from similar subjects. Study (1) Young (N = 27, 23 ± 8 years) and older adults (N = 14, 72 ± 9 years) underwent assessment of maximum voluntary contraction force (MVC) and force steadiness during constant-force (CF) index finger abduction (2.5, 30, 65% MVC). For each trial, visual feedback of the force (VIS) was provided for 8–10 s and removed for 8–10 s (NOVIS). Visual gain of the force feedback at 2.5% MVC was high; 12- and 26-fold greater than the 30 and 65% MVC targets. Mean force, standard deviation (SD) of force, and coefficient of variation (CV) of force was calculated for detrended (<0.5 Hz drift removed) VIS and NOVIS data segments. Study (2) A similar group of 14 older adults performed discrete, randomly-ordered VIS or NOVIS trials at low target forces (1–3% MVC) and high visual gain. Study (1) For young adults the CV of force was similar between VIS and NOVIS for the 2.5% (4.8 vs. 4.3%), 30% (3.2 vs. 3.2%) and 65% (3.5 vs. 4.2%) target forces. In contrast, for older adults the CV of force was greater for VIS than NOVIS for 2.5% MVC (6.6 vs. 4.2%, p < 0.001), but not for the 30% (2.4 vs. 2.4%) and 65% (3.1 vs. 3.3%) target forces. At 2.5% MVC, the increase in CV of force for VIS compared with NOVIS was significantly greater (age × visual condition p = 0.008) for older than young adults. Study (2) Similarly, for older adults performing discrete, randomly ordered trials the CV of force was greater for VIS than NOVIS (6.04 vs. 3.81%, p = 0.01). When visual force feedback was a dominant source of information at low forces, normalized force variability was ~58% greater for older adults, but only 11% greater for young adults. The significant effect of visual feedback for older adults was not dependent on the order of presentation of visual conditions. The results indicate that impaired processing of visuomotor information underlies the greater motor variability observed in older adults during lab-based isometric contractions of a hand muscle.

High-Frequency Repetitive Transcranial Magnetic Stimulation Effects on Motor Intracortical Neurophysiology: A Sham-Controlled Investigation.

Purpose: The purpose of this study was to investigate the effects of high-frequency repetitive transcranial magnetic stimulation (rTMS) versus sham stimulation on intracortical inhibition (ICI) and intracortical facilitation within the motor cortex. Such data are needed to better understand the presumed neurophysiologic effects of rTMS. Methods: The authors hypothesized that, compared with sham stimulation, 20 Hz rTMS will decrease ICI and increase intracortical facilitation in healthy volunteers. Using single-pulse and paired-pulse TMS, the authors evaluated prestimulation and poststimulation effects on motor cortex neurophysiology in neurologically healthy volunteers who received 2,000 stimuli of either 20 Hz rTMS (n = 11) or sham rTMS (n = 8). Primary outcomes were changes in ICI and intracortical facilitation and secondary outcomes were changes in motor threshold and motor evoked potential amplitude, and both were assessed using separate 2 × 2 (group × time) repeated-measures analysis of variance. Results: For ICI, there were main effects of time (P = 0.002) and group (P < 0.001) with a significant group-by-time interaction (P < 0.01). Intracortical inhibition decreased after rTMS, but was unchanged by sham rTMS. Intracortical facilitation results revealed a main effect of group (P = 0.02) and a significant group-by-time interaction (P = 0.048). Intracortical facilitation increased after rTMS and was slightly reduced after sham rTMS. The group-by-time interactions for motor threshold and motor evoked potential amplitude were not significant. Conclusions: High-frequency rTMS significantly influences the excitatory and inhibitory outputs of motor intracortical networks, specifically increasing intracortical facilitation and reducing ICI as compared with sham stimulation. Such changes were observed despite no significant changes in broader measures of motor cortex activation, that is, motor threshold and motor evoked potential amplitude.

Physical activity, ambulation, and comorbidities in people with diabetes and lower-limb amputation

We characterized physical activity (PA) and its relation to physical function and number of comorbidities in people with diabetes and transtibial amputation (AMP), people with diabetes without AMP, and nondisabled adults without diabetes or AMP. Twenty-two individuals with type 2 diabetes mellitus (DM) and transtibial amputation (DM+AMP), 11 people with DM, and 13 nondisabled participants were recruited for this cross-sectional cohort study. Measures included PA volume and intensity, a Timed Up and Go test, a 2-min walk test, and number of comorbidities. The nondisabled group performed greater amounts of PA than the DM group, who performed greater amounts of PA than the DM+AMP group. PA was related to physical function in the DM group and in the DM+AMP group, whereas no such relationship existed in the nondisabled group. PA was not related to number of comorbidities in any group. These findings suggest the ability to walk may affect overall performance of PA. Alternately, PA may alleviate walking problems. This possibility is of interest because issues with walking may be modifiable by improved levels and intensity of PA. PAs lack of relation to number of comorbidities suggests that factors beyond multiple morbidities account for group differences in PA.