Kristel Knaepen

Neuroplasticity - exercise-induced response of peripheral brain-derived neurotrophic factor: a systematic review of experimental studies in human subjects.

Exercise is known to induce a cascade of molecular and cellular processes that support brain plasticity. Brain-derived neurotrophic factor (BDNF) is an essential neurotrophin that is also intimately connected with central and peripheral molecular processes of energy metabolism and homeostasis, and could play a crucial role in these induced mechanisms.This review provides an overview of the current knowledge on the effects of acute exercise and/or training on BDNF in healthy subjects and in persons with a chronic disease or disability. A systematic and critical literature search was conducted. Articles were considered for inclusion in the review if they were human studies, assessed peripheral (serum and/or plasma) BDNF and evaluated an acute exercise or training intervention. Nine RCTs, one randomized trial, five non-randomized controlled trials, five non-randomized non-controlled trials and four retrospective observational studies were analysed. Sixty-nine percent of the studies in healthy subjects and 86%of the studies in persons with a chronic disease or disability, showed a ‘mostly transient’ increase in serum or plasma BDNF concentration following an acute aerobic exercise. The two studies regarding a single acute strength exercise session could not show a significant influence on basal BDNF concentration. In studies regarding the effects of strength or aerobic training on BDNF, a difference should be made between effects on basal BDNF concentration and training-induced effects on the BDNF response following an acute exercise. Only three out of ten studies on aerobic or strength training (i.e. 30%) found a training-induced increase in basal BDNF concentration. Two out of six studies (i.e. 33%) reported a significantly higher BDNF response to acute exercise following an aerobic or strength training programme (i.e. compared with the BDNF response to an acute exercise at baseline). A few studies of low quality (i.e. retrospective observational studies) show that untrained or moderately trained healthy subjects have higher basal BDNF concentrations than highly trained subjects. Yet, strong evidence still has to come from good methodological studies.Available results suggest that acute aerobic, but not strength exercise increases basal peripheral BDNF concentrations, although the effect is transient. From a few studies we learn that circulating BDNF originates both from central and peripheral sources. We can only speculate which central regions and peripheral sources in particular circulating BDNF originates from, where it is transported to and to what purpose it is used and/or stored at its final destination. No study could show a long-lasting BDNF response to acute exercise or training (i.e. permanently increased basal peripheral BDNF concentration) in healthy subjects or persons with a chronic disease or disability. It seems that exercise and/or training temporarily elevate basal BDNF and possibly upregulate cellular processing of BDNF (i.e. synthesis, release, absorption and degradation). From that point of view, exercise and/or training would result in a higher BDNF synthesis following an acute exercise bout (i.e. compared with untrained subjects). Subsequently, more BDNF could be released into the blood circulation which may, in turn, be absorbed more efficiently by central and/or peripheral tissues where it could induce a cascade of neurotrophic and neuroprotective effects.

Brain-derived neurotrophic factor as a driving force behind neuroplasticity in neuropathic and central sensitization pain: a new therapeutic target?

Introduction: Central sensitization is a form of maladaptive neuroplasticity underlying many chronic pain disorders, including neuropathic pain, fibromyalgia, whiplash, headache, chronic pelvic pain syndrome and some forms of osteoarthritis, low back pain, epicondylitis, shoulder pain and cancer pain. Brain-derived neurotrophic factor (BDNF) is a driving force behind neuroplasticity, and it is therefore crucial for neural maintenance and repair. However, BDNF also contributes to sensitization of pain pathways, making it an interesting novel therapeutic target. Areas covered: An overview of BDNF’s sensitizing capacity at every level of the pain pathways is presented, including the peripheral nociceptors, dorsal root ganglia, spinal dorsal horn neurons, and brain descending inhibitory and facilitatory pathways. This is followed by the presentation of several potential therapeutic options, ranging from indirect influencing of BDNF levels (using exercise therapy, anti-inflammatory drugs, melatonin, repetitive transcranial magnetic stimulation) to more specific targeting of BDNF’s receptors and signaling pathways (blocking the proteinase-activated receptors 2–NK-κβ signaling pathway, administration of phencyclidine for antagonizing NMDA receptors, or blockade of the adenosine A2A receptor). Expert opinion: This section focuses on combining pharmacotherapy with multimodal rehabilitation for balancing the deleterious and therapeutic effects of BNDF treatment in chronic pain patients, as well as accounting for the complex and biopsychosocial nature of chronic pain.

Safe and Compliant Guidance by a Powered Knee Exoskeleton for Robot-Assisted Rehabilitation of Gait

In the research field of robot-assisted gait rehabilitation there is increased focus on the improvement of physical human–robot interaction by means of high-performance actuator technologies and dedicated control strategies. In this context we propose a combination of lightweight, intrinsically compliant, high-torque actuators (pleated pneumatic artificial muscles) with safe and adaptable guidance along a target trajectory by means of proxy-based sliding mode control. We developed a powered knee exoskeleton (KNEXO) to evaluate these concepts. In addition to the trajectory-based controller a torque controller was implemented with a view to minimizing the interaction during unassisted walking. First, various treadmill walking experiments were performed with unimpaired subjects wearing KNEXO to evaluate the performance of the proposed controllers. Test results confirm the ability of KNEXO to display low actuator torques in unassisted mode and to provide safe, adaptable guidance in assisted mode. Subsequently, a multiple sclerosis patient participated in a series of pilot experiments. Provided there was some patient-specific controller tuning KNEXO was found to effectively support and compliantly guide the subjects knee.

Human–Robot Interaction: Kinematics and Muscle Activity Inside a Powered Compliant Knee Exoskeleton

Until today it is not entirely clear how humans interact with automated gait rehabilitation devices and how we can, based on that interaction, maximize the effectiveness of these exoskeletons. The goal of this study was to gain knowledge on the human-robot interaction, in terms of kinematics and muscle activity, between a healthy human motor system and a powered knee exoskeleton (i.e., KNEXO). Therefore, temporal and spatial gait parameters, human joint kinematics, exoskeleton kinetics and muscle activity during four different walking trials in 10 healthy male subjects were studied. Healthy subjects can walk with KNEXO in patient-in-charge mode with some slight constraints in kinematics and muscle activity primarily due to inertia of the device. Yet, during robot-in-charge walking the muscular constraints are reversed by adding positive power to the leg swing, compensating in part this inertia. Next to that, KNEXO accurately records and replays the right knee kinematics meaning that subject-specific trajectories can be implemented as a target trajectory during assisted walking. No significant differences in the human response to the interaction with KNEXO in low and high compliant assistance could be pointed out. This is in contradiction with our hypothesis that muscle activity would decrease with increasing assistance. It seems that the differences between the parameter settings of low and high compliant control might not be sufficient to observe clear effects in healthy subjects. Moreover, we should take into account that KNEXO is a unilateral, 1 degree-of-freedom device.

Effects of caffeine and maltodextrin mouth rinsing on P300, brain imaging, and cognitive performance

Caffeine (CAF) and maltodextrin (MALT) mouth rinses (MR) improve exercise performance. The current experiment aims to determine the effect of CAF and MALT MR on cognitive performance and brain activity. Ten healthy male subjects (age 27 ± 3 yr) completed three experimental trials. Each trial included four Stroop tasks: two familiarization tasks, and one task before and one task after an MR period. The reaction time (in milliseconds) and accuracy (percent) of simple, congruent, and incongruent stimuli were assessed. Electroencephalography was applied throughout the experiment to record brain activity. The amplitudes and latencies of the P300 were determined during the Stroop tasks before and after the MR period. Subjects received MR with CAF (0.3 g/25 ml), MALT (1.6 g/25 ml), or placebo (PLAC) in a randomized, double-blind, crossover design. During MR, the brain imaging technique standardized low-resolution brain electromagnetic tomography was applied. Magnitude-based inferences showed that CAF MR is likely trivial (63.5%) and likely beneficial (36.4%) compared with PLAC MR, and compared with MALT MR likely beneficial to reaction time on incongruent stimuli (61.6%). Additionally, both the orbitofrontal and dorsolateral prefrontal cortex were activated only during CAF MR, potentially explaining the likely beneficial effect on reaction times. MALT MR increased brain activity only within the orbitofrontal cortex. However, this brain activation did not alter the reaction time. Furthermore, no significant differences in the accuracy of stimuli responses were observed between conditions. In conclusion, only CAF MR exerted a likely beneficial effect on reaction time due to the subsequent activation of both the orbitofrontal and dorsolateral prefrontal cortexes.

Does a period of detraining cause a decrease in serum brain-derived neurotrophic factor?

Brain-derived neurotrophic factor (BDNF) is one of the neurotrophins promoting cognitive function and contributing to neurogenesis and neuroprotection. Available evidence suggests that exercise influences serum BDNF concentrations, but that the effect is transient. The purpose of this study is to determine whether a period of aerobic training, followed by a period of detraining, can influence basal serum BDNF levels in humans. Sixteen young, sedentary subjects were assigned to an experimental group (n=9) and a control group (n=7). The experimental group performed an aerobic training program during 8 weeks, followed by 8 weeks of detraining, during which subjects returned to their previous, sedentary activity level. The control group remained physically inactive during 16 weeks. In both groups, performance on short-term (Digit Span test) and mid-term memory (Recall of Images) was assessed. Aerobic training significantly increased the VO(2) peak in the experimental group, and these values returned to baseline after 8 weeks of detraining. Basal serum BDNF was not influenced by 8 weeks of aerobic training and detraining did not seem to have an effect on basal peripheral BDNF concentrations. Both training and detraining did not clearly influence short-term memory performance on the Digit Span test and no differences were present between the experimental and control group on the mid-term memory test. Future studies should focus on patient groups and elderly to further investigate the effect of training and detraining on neurotrophic factors and cognitive function, and on the effects of training and detraining on the BDNF response to acute exercise.

Brain mapping after prolonged cycling and during recovery in the heat

The aim of this study was to determine the effect of prolonged intensive cycling and postexercise recovery in the heat on brain sources of altered brain oscillations. After a max test and familiarization trial, nine trained male subjects (23 ± 3 yr; maximal oxygen uptake = 62.1 ± 5.3 ml·min(-1)·kg(-1)) performed three experimental trials in the heat (30°C; relative humidity 43.7 ± 5.6%). Each trial consisted of two exercise tasks separated by 1 h. The first was a 60-min constant-load trial, followed by a 30-min simulated time trial (TT1). The second comprised a 12-min simulated time trial (TT2). After TT1, active recovery (AR), passive rest (PR), or cold water immersion (CWI) was applied for 15 min. Electroencephalography was measured at baseline and during postexercise recovery. Standardized low-resolution brain electromagnetic tomography was applied to accurately pinpoint and localize altered electrical neuronal activity. After CWI, PR and AR subjects completed TT2 in 761 ± 42, 791 ± 76, and 794 ± 62 s, respectively. A prolonged intensive cycling performance in the heat decreased β activity across the whole brain. Postexercise AR and PR elicited no significant electrocortical differences, whereas CWI induced significantly increased β3 activity in Brodmann areas (BA) 13 (posterior margin of insular cortex) and BA 40 (supramarginal gyrus). Self-paced prolonged exercise in the heat seems to decrease β activity, hence representing decreased arousal. Postexercise CWI increased β3 activity at BA 13 and 40, brain areas involved in somatosensory information processing.

Human-Robot Interaction: Does Robotic Guidance Force Affect Gait-Related Brain Dynamics during Robot-Assisted Treadmill Walking?

In order to determine optimal training parameters for robot-assisted treadmill walking, it is essential to understand how a robotic device interacts with its wearer, and thus, how parameter settings of the device affect locomotor control. The aim of this study was to assess the effect of different levels of guidance force during robot-assisted treadmill walking on cortical activity. Eighteen healthy subjects walked at 2 km.h-1 on a treadmill with and without assistance of the Lokomat robotic gait orthosis. Event-related spectral perturbations and changes in power spectral density were investigated during unassisted treadmill walking as well as during robot-assisted treadmill walking at 30%, 60% and 100% guidance force (with 0% body weight support). Clustering of independent components revealed three clusters of activity in the sensorimotor cortex during treadmill walking and robot-assisted treadmill walking in healthy subjects. These clusters demonstrated gait-related spectral modulations in the mu, beta and low gamma bands over the sensorimotor cortex related to specific phases of the gait cycle. Moreover, mu and beta rhythms were suppressed in the right primary sensory cortex during treadmill walking compared to robot-assisted treadmill walking with 100% guidance force, indicating significantly larger involvement of the sensorimotor area during treadmill walking compared to robot-assisted treadmill walking. Only marginal differences in the spectral power of the mu, beta and low gamma bands could be identified between robot-assisted treadmill walking with different levels of guidance force. From these results it can be concluded that a high level of guidance force (i.e., 100% guidance force) and thus a less active participation during locomotion should be avoided during robot-assisted treadmill walking. This will optimize the involvement of the sensorimotor cortex which is known to be crucial for motor learning.

Walking with robot assistance: the influence of body weight support on the trunk and pelvis kinematics.

Abstract Purpose: The goal was to assess in healthy participants the three-dimensional kinematics of the pelvis and the trunk during robot-assisted treadmill walking (RATW) at 0%, 30% and 50% body weight support (BWS), compared with treadmill walking (TW). Methods: 18 healthy participants walked (2 kmph) on a treadmill with and without robot assistance (Lokomat; 60% guidance force; 0%, 30% and 50% BWS). After an acclimatisation period (four minutes), trunk and pelvis kinematics were registered in each condition (Polhemus Liberty™ [240 Hz]). The results were analysed using a repeated measures analysis of variance with Bonferroni correction, with the level of suspension as within-subject factor. Results: During RATW with BWS, there were significantly (1) smaller antero-posterior and lateral translations of the trunk and the pelvis; (2) smaller antero-posterior flexion and axial rotation of the trunk; (3) larger lateral flexion of the trunk; and (4) larger antero-posterior tilting of the pelvis compared with TW. Conclusions: There are significant differences in trunk and pelvis kinematics in healthy persons during TW with and without robot assistance. These data are relevant in gait rehabilitation, relating to normal balance regulation. Additional research is recommended to further assess the influence of robot assistance on human gait. Implications for Rehabilitation The trunk and pelvis moves in a different way during walking with robot assistance. The data suggest that the change in movement is due to the robot device and the harness of the suspension system more than due to the level of suspension itself.

Robot-assisted walking with the Lokomat: the influence of different levels of guidance force on thorax and pelvis kinematics.

BACKGROUND Little attention has been devoted to the thorax and pelvis movements during gait. The aim of this study is to compare differences in the thorax and pelvis kinematics during unassisted walking on a treadmill and during walking with robot assistance (Lokomat-system (Hocoma, Volketswil, Switzerland)). METHODS 18 healthy persons walked on a treadmill with and without the Lokomat system at 2kmph. Three different conditions of guidance force (30%, 60% and 100%) were used during robot-assisted treadmill walking (30% body weight support). The maximal movement amplitudes of the thorax and pelvis were measured (Polhemus Liberty™ (Polhemus, Colchester, Vermont, USA) (240/16)). A repeated measurement ANOVA was conducted. FINDINGS Robot-assisted treadmill walking with different levels of guidance force showed significantly smaller maximal movement amplitudes for thorax and pelvis, compared to treadmill walking. Only the antero-posterior tilting of the pelvis was significantly increased during robot-assisted treadmill walking compared to treadmill walking. No significant changes of kinematic parameters were found between the different levels of guidance force. INTERPRETATION With regard to the thorax and pelvis movements, robot-assisted treadmill walking is significantly different compared to treadmill walking. It can be concluded that when using robot assistance, the thorax is stimulated in a different way than during walking without robot assistance, influencing the balance training during gait.