Prefrontal Cortex Activity Predicts Mental Fatigue in Young and Elderly Men During a 2 h “Go/NoGo” Task

Background: Although the effects of mental fatigue on cognitive–motor function and psychological state in young adults are well-documented, its effects in the elderly are not completely understood. The aim of this study was to estimate the effect of prolonged cognitive load on the indicators of psychological, cognitive, and motor functions.Methods: Fifteen young and 15 elderly men were asked to perform a 2 h “Go/NoGo” task. Psychological state (mood and motivation), cognitive (prefrontal cortex activity and cognitive performance), and motor (motor cortex excitability and grip strength) functions were measured before and after the task. During the 2 h task, both groups had a significantly similar increase in the number of “Incorrect NoGo” errors. Only in young men reaction time (RT) of “Incorrect NoGo” and intraindividual variability of RT of “Incorrect NoGo” significantly increased during task. After the task, handgrip strength decreased for the young men, whereas latency of motor evoked potentials prolonged both groups. Nevertheless, both groups indicated that they felt fatigue after the 2 h task; we observed that mental demand increased, whereas intrinsic motivation and mood decreased only in young men. Prolonged task decreased the switching/rest ratio of oxygenated hemoglobin for the young and the elderly men; however, greater for elderly than young men. Interestingly, the more the prefrontal cortex was activated before the 2 h task during the switching task, the fewer of “Incorrect NoGo” errors made by the young men and the greater the number of errors made by the elderly men.Conclusion: Because of the greater mental load and (possibly) greater activation of prefrontal cortex during the 2 h “Go/NoGo” task, there was greater mental and neuromuscular performance fatigue in young men than in elderly men

Rapid and sustained B-cell depletion with subcutaneous ofatumumab in relapsing multiple sclerosis : APLIOS, a randomized phase-2 study

Background: Ofatumumab, the first fully human anti-CD20 monoclonal antibody, is approved in several countries for relapsing multiple sclerosis (RMS). Objective: To demonstrate the bioequivalence of ofatumumab administered by an autoinjector versus a pre-filled syringe (PFS) and to explore the effect of ofatumumab on B-cell depletion. Methods: APLIOS (NCT03560739) is a 12-week, open-label, parallel-group, phase-2 study in patients with RMS receiving subcutaneous ofatumumab 20 mg every 4 weeks (q4w) (from Week 4, after initial doses on Days 1, 7, and 14). Patients were randomized 10:10:1:1 to autoinjector or PFS in the abdomen, or autoinjector or PFS in the thigh, respectively. Bioequivalence was determined by area under the curve (AUCτ) and maximum plasma concentration (Cmax) for Weeks 8-12. B-cell depletion and safety/tolerability were assessed. Results: A total of 256 patients contributed to the bioequivalence analyses (autoinjector-abdomen, n = 128; PFS-abdomen, n = 128). Abdominal ofatumumab pharmacokinetic exposure was bioequivalent for autoinjector and PFS (geometric mean AUCτ, 487.7 vs 474.1 h × µg/mL (ratio 1.03); Cmax, 1.409 vs 1.409 µg/mL (ratio 1.00)). B-cell counts (median cells/µL) depleted rapidly in all groups from 214.0 (baseline) to 2.0 (Day 14). Ofatumumab was well tolerated. Conclusion: Ofatumumab 20 mg q4w self-administered subcutaneously via autoinjector is bioequivalent to PFS administration and provides rapid B-cell depletion

Two strategies for response to 14 °C cold-water immersion: is there a difference in the response of motor, cognitive, immune and stress markers?

Here, we address the question of why some people have a greater chance of surviving and/or better resistance to cold-related-injuries in prolonged exposure to acute cold environments than do others, despite similar physical characteristics. The main aim of this study was to compare physiological and psychological reactions between people who exhibited fast cooling (FC; n = 20) or slow cooling (SC; n = 20) responses to cold water immersion. Individuals in whom the T(re) decreased to a set point of 35.5 °C before the end of the 170-min cooling time were indicated as the FC group; individuals in whom the T(re) did not decrease to the set point of 35.5 °C before the end of the 170-min cooling time were classified as the SC group. Cold stress was induced using intermittent immersion in bath water at 14 °C. Motor (spinal and supraspinal reflexes, voluntary and electrically induced skeletal muscle contraction force) and cognitive (executive function, short term memory, short term spatial recognition) performance, immune variables (neutrophils, leucocytes, lymphocytes, monocytes, IL-6, TNF-α), markers of hypothalamic-pituitary-adrenal axis activity (cortisol, corticosterone) and autonomic nervous system activity (epinephrine, norepinephrine) were monitored. The data obtained in this study suggest that the response of the FC group to cooling vs the SC group response was more likely an insulative-hypothermic response and that the SC vs the FC group displayed a metabolic-insulative response. The observations that an exposure time to 14 °C cold water--which was nearly twice as short (96-min vs 170-min) with a greater rectal temperature decrease (35.5 °C vs 36.2 °C) in the FC group compared with the SC group--induces similar responses of motor, cognitive, and blood stress markers were novel. The most important finding is that subjects with a lower cold-strain-index (SC group) showed stimulation of some markers of innate immunity and suppression of markers of specific immunity

Research design.

<p>BS – blood samples, T_re – rectal temperature, T_mu – muscle temperature, T_sk – skin temperature. Cognitive function (CF) testing involved the unpredictable task switching test (executive function), the forward digit-span task test (short term memory), and the forced-choice recognition memory test (short term spatial recognition). Neuromuscular (NM) testing involved evaluation of spinal (H-reflexes, M-waves) and supraspinal (V-waves) excitability, evaluation of muscle contractility characteristics induced by a 1-s electrical stimulation at 1 Hz, 20 Hz, 100 Hz and TT-100 Hz; evaluation of maximal voluntary contraction torque and central activation of exercising muscle was performed with a TT-100 Hz superimposed stimulation on the maximal voluntary contraction. Intermittent head-out immersion in bath water at 14°C continued until the rectal temperature decreased to 35.5°C or until 170 min total (120 min maximum total immersion time), at which time the immersion ended regardless of the rectal temperature.</p

Adding high-intensity interval training to classical resistance training does not impede the recovery from inactivity-induced leg muscle weakness

Inactivity is known to induce muscle weakness, and chronically increased levels of reactive oxygen species (ROS) are proposed to have a central causative role in this process. Intriguingly, high-intensity interval training (HIIT), which involves bursts of high ROS production, can have positive effects in pathological conditions with chronically increased ROS. Here, young male volunteers were exposed to 3 weeks of unloading of the dominant leg followed by 3 weeks of resistance training without (Ctrl group) or with the addition of all-out cycling HIIT. Changes in muscle thickness were assessed by ultrasonography, and contractile function was studied by measuring the torque during maximal voluntary contractions (MVC). The results show an ~6% decrease in vastus lateralis thickness after the unloading period, which was fully restored after the subsequent training period in both the Ctrl and HIIT groups. MVC torque was decreased by ~11% after the unloading period and recovered fully during the subsequent training period in both groups. All-out cycling performance was improved by the 3 weeks of HIIT. In conclusion, the decline in muscle size and function after 3 weeks of unloading was restored by 3 weeks of resistance training regardless of whether it was combined with HIIT

VO₂, metabolic heat production and metabolic shivering before and during body cooling.

<p>*P<0.05, compared with before;</p>#<p>P<0.05 between fast cooling (FC) and slow cooling (SC) groups. Values are means ± SD.</p><p>VO₂, metabolic heat production and metabolic shivering before and during body cooling.</p

Spinal reflex excitability before and after body cooling.

<p>*P<0.05, compared with before. Fast cooling group (FC); Slow cooling group (SC). Values are means ± SD.</p><p>Spinal reflex excitability before and after body cooling.</p

One night of sleep deprivation impairs executive function but does not affect psychomotor or motor performance

The current study assessed the impact of one night of sleep deprivation on cognitive, motor and psychomotor performance. Thirty healthy young adult male subjects completed a 24 h control or 24 h sleep deprived trial. For the control trial, participants (N = 15) were allowed normal night sleep (~8 h). For the sleep deprived trial, participants (N = 15) did not sleep for 24 h. Cognitive performance during go/no-go, Stroop and simple reaction tasks, psychomotor performance during speed-accuracy tasks with fxed and unfxed targets, and motor performance during countermovement jump, hand grip strength, and 30-s maximal voluntary contraction tasks were evaluated on day 1 at 8 am and 7 pm and on day 2 at 8 am. One night of sleep deprivation impaired psychological well-being and executive function but did not affect simple reaction time, the capacity for arm and leg muscle contraction, motor control performance during a speed–accuracy task with both fxed and unfxed targets, and central and peripheral motor fatigue in the 30 s maximal voluntary contraction task. The present study showed that one night of sleep deprivation resulted in executive function deterioration but did not modify motor control or maximal effort requiring performance of motor tasks

Body temperatures before and after body cooling.

<p>*P<0.05, compared with before;</p>#<p>P<0.05 between fast cooling (FC) and slow cooling (SC) groups. T_re – rectal temperature, T_mu – muscle temperature, T_sk – skin temperature. Values are means ± SD.</p><p>Body temperatures before and after body cooling.</p

Voluntary and electrically induced skeletal muscle properties before and after cooling.

<p>*P<0.05, compared with before; MVC – maximal voluntary contraction, CAR – central activation ratio; P1, P20, P100 – 1 Hz, 20 Hz, 100 Hz electrical stimulus, respectively; P1/P100 – 1/100 Hz ratio; HRT – Half-relaxation time. Fast cooling group (FC); Slow cooling group (SC). Values are means ± SD.</p><p>Voluntary and electrically induced skeletal muscle properties before and after cooling.</p