Interhemispheric transfer time correlates with white matter integrity of the corpus callosum in healthy older adults.

The corpus callosum (CC) has been identified as an important structure in the context of cognitive aging (Fling et al., 2011). Interhemispheric transfer time (IHTT) is regularly used in order to estimate interhemispheric integration enabled by the CC (Marzi, 2010; Nowicka and Tacikowski, 2011). However, only little is known with regards to the relationship between IHTT and the structural properties of the CC with only few studies with specific samples and methods available (Whitford et al., 2011). Thus, the present study aimed at investigating this relationship applying an event-related potentials (ERP) based approach of estimating IHTT as well as diffusion weighted imaging (DWI) with fractional anisotropy (FA) as an indicator of white matter integrity (WMI) of the genu, corpus and splenium of the CC. 56 healthy older adults performed a Dimond Task while ERPs were recorded and underwent DWI scanning. IHTT derived from posterior electrode sites correlated significantly with FA of the splenium (r = -0.286*, p = .03) but not the corpus (r = -0.187, p = .08) or genu (r = -0.189, p = .18). The present results support the notion that IHTT is related to WMI of the posterior CC. It may be concluded that ERP based IHTT is a suitable indicator of CC structure and function, however, likely specific to the interhemispheric transfer of visual information. Future studies may wish to confirm these findings in a more divers sample further exploring the precise interrelation between IHTT and structural or functional properties of the CC.

The relationship between interhemispheric transfer time and physical activity as well as cardiorespiratory fitness in healthy older adults.

The structural and functional degradation of the corpus callosum (CC) has been shown to play an important role in the context of cognitive aging (Reuter-Lorenz and Stanczak, 2000). This is also reflected by findings of elongated interhemispheric transfer time (IHTT) in older adults (Riedel et al., 2022). At the same time, a protective effect of physical activity (PA) and cardiorespiratory fitness (CRF) on brain health including the CC is widely accepted (Hillman et al., 2008; Loprinzi et al., 2020). Based on this idea, the present study investigated the relationship between IHTT and PA/CRF in 107 healthy older adults (m: 64, f: 43) aged 67.69 ± 5.18. IHTT was calculated detecting event-related potentials (ERPs) using an established Dimond-Task. PA was evaluated using accelerometry resulting in estimates of overall bodily motion and time spent at higher intensity PA. CRF was estimated using graded exercise testing, approximating running speed at 4 mmol/l blood lactate concentration. The results showed a negative correlation between IHTTright→left and PA overall as well as in the male subgroup and between IHTTleft→right and CRF in women. This indicates a potential relationship between IHTT and PA/CRF. While the present investigation is only the first to hint at such a relationship taking into account the differential effects with regards to sex, mode of PA/CRF and IHTT direction, it is in line with previous findings and theoretical suggestions linking brain health to PA/CRF in the context of aging. Further research is needed in order to increase our understanding of the underlying mechanisms and of the influence of sex, PA intensity, degree of CRF and significance of IHTT direction.

The impact of aging on interhemispheric transfer time and respective sex differences.

Age-related cognitive decline has been attributed to degeneration of the corpus callosum (CC), which allows for interhemispheric integration and information processing [22,69]. Along with decreased structural integrity, altered functional properties of the CC may cause impaired cognitive performance in older adults, yet this aspect of age-related decline remains insufficiently researched [59]. In this context, potential sex-related differences have been proposed [31,58]. A promising parameter, which has been suggested to estimate functional properties of the CC is the interhemispheric transfer time (IHTT), which is ideally obtained from event-related potentials (ERP) evoked by lateralized stimuli [45]. To examine the possible functional consequences of aging with regards to the CC, the present study investigated the IHTT of 107 older (67.69 ±â€¯5.18y) as well as of 23 younger participants (25.09 ±â€¯2.59y). IHTT was obtained using an established letter matching task and targeting early N170 ERP components at posterior electrode sites. The results revealed significantly elongated IHTT in older compared to younger participants, but no significant sex differences. Furthermore, there was a significant positive correlation between IHTT and age, predominantly driven by the female participants. The present findings add support to the notion, that IHTT is subject to age-related elongation reflecting impaired interhemispheric transmission. Age-related decline in women appears to occur at a different age range compared to men.

Dorsolateral Prefrontal Functional Connectivity Predicts Working Memory Training Gains.

Background: Normal aging is associated with working memory decline. A decrease in working memory performance is associated with age-related changes in functional activation patterns in the dorsolateral prefrontal cortex (DLPFC). Cognitive training can improve cognitive performance in healthy older adults. We implemented a cognitive training study to assess determinants of generalization of training gains to untrained tasks, a key indicator for the effectiveness of cognitive training. We aimed to investigate the association of resting-state functional connectivity (FC) of DLPFC with working memory performance improvement and cognitive gains after the training. Method: A sample of 60 healthy older adults (mean age: 68 years) underwent a 4-week neuropsychological training, entailing a working memory task. Baseline resting-state functional MRI (rs-fMRI) images were acquired in order to investigate the FC of DLPFC. To evaluate training effects, participants underwent a neuropsychological assessment before and after the training. A second follow-up assessment was applied 12 weeks after the training. We used cognitive scores of digit span backward and visual block span backward tasks representing working memory function. The training group was divided into subjects who had and who did not have training gains, which was defined as a higher improvement in working memory tasks than the control group (N = 19). Results: A high FC of DLPFC of the right hemisphere was significantly associated with training gains and performance improvement in the visuospatial task. The maintenance of cognitive gains was restricted to the time period directly after the training. The training group showed performance improvement in the digit span backward task. Conclusion: Functional activation patterns of the DLPFC were associated with the degree of working memory training gains and visuospatial performance improvement. Although improvement through cognitive training and acquisition of training gains are possible in aging, they remain limited.

The Impact of Age on the Association Between Physical Activity and White Matter Integrity in Cognitively Healthy Older Adults.

Cognition emerges from coordinated processing among distributed cortical brain regions, enabled through interconnected white matter networks. Cortical disconnection caused by age-related decline in white matter integrity (WMI) is likely to contribute to age-related cognitive decline. Physical activity (PA) has been suggested to have beneficial effects on white matter structure. However, its potential to counteract age-related decline in WMI is not yet well established. The present explorative study analyzed if PA was associated with WMI in cognitively healthy older adults and if this association was modulated by age. Forty-four cognitively healthy older individuals (aged 60-88 years) with diffusion-tensor imaging (DTI) and PA measurements were included from the AgeGain study. Voxelwise analysis using Tract-Based Spatial Statistics (TBSS) demonstrated that PA was associated with WMI in older adults. However, results emphasized that this association was restricted to high age. The association between PA and WMI was found in widespread white matter regions suggesting a global rather than a regional effect. Supplementary analyses demonstrated an association between the integrity of these regions and the performance in memory [verbal learning and memory test (VLMT)] and executive functioning (Tower of London).Results of the present explorative study support the assumption that PA is associated with WMI in older adults. However, results emphasize that this association is restricted to high age. Since cognitive decline in the elderly is typically most pronounced in later stages of aging, PA qualifies as a promising tool to foster resilience against age-related cognitive decline, via the preservation of the integrity of the brains WM.

Improving Challenge/Skill Ratio in a Multimodal Interface by Simultaneously Adapting Game Difficulty and Haptic Assistance through Psychophysiological and Performance Feedback.

In order to harmonize robotic devices with human beings, the robots should be able to perceive important psychosomatic impact triggered by emotional states such as frustration or boredom. This paper presents a new type of biocooperative control architecture, which acts toward improving the challenge/skill relation perceived by the user when interacting with a robotic multimodal interface in a cooperative scenario. In the first part of the paper, open-loop experiments revealed which physiological signals were optimal for inclusion in the feedback loop. These were heart rate, skin conductance level, and skin conductance response frequency. In the second part of the paper, the proposed controller, consisting of a biocooperative architecture with two degrees of freedom, simultaneously modulating game difficulty and haptic assistance through performance and psychophysiological feedback, is presented. With this setup, the perceived challenge can be modulated by means of the game difficulty and the perceived skill by means of the haptic assistance. A new metric (FlowIndex) is proposed to numerically quantify and visualize the challenge/skill relation. The results are contrasted with comparable previously published work and show that the new method afforded a higher FlowIndex (i.e., a superior challenge/skill relation) and an improved balance between augmented performance and user satisfaction (higher level of valence, i.e., a more enjoyable and satisfactory experience).

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.

Temporal and spatial organization of gait-related electrocortical potentials.

To advance gait rehabilitation research it is of great importance to understand the supraspinal control of walking. In this study, the temporal and spatial characteristics of averaged electrocortical activity during treadmill walking in healthy subjects was assessed. Electroencephalography data were recorded from 32 scalp locations, averaged across trials, and related to phases of the gait cycle based on the detection of left heel strike. A characteristic temporal pattern of positive and negative potentials, similar to movement-related cortical potentials, and related to the gait cycle was observed over the cortical leg representation area. Source localization analysis revealed that mainly the primary somatosensory, somatosensory association, primary motor and cingulate cortex were activated during walking. The negative peaks of the gait-related cortical potential were associated with activity predominantly in the cingulate and prefrontal cortex, while the primary motor, primary somatosensory and somatosensory association cortex were mainly active during the positive peaks. This study identified gait-related cortical potentials during walking. The results indicate a widely distributed cortical network involved in gait control.

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.

Psychophysiological response to cognitive workload during symmetrical, asymmetrical and dual-task walking.

Walking with a lower limb prosthesis comes at a high cognitive workload for amputees, possibly affecting their mobility, safety and independency. A biocooperative prosthesis which is able to reduce the cognitive workload of walking could offer a solution. Therefore, we wanted to investigate whether different levels of cognitive workload can be assessed during symmetrical, asymmetrical and dual-task walking and to identify which parameters are the most sensitive. Twenty-four healthy subjects participated in this study. Cognitive workload was assessed through psychophysiological responses, physical and cognitive performance and subjective ratings. The results showed that breathing frequency and heart rate significantly increased, and heart rate variability significantly decreased with increasing cognitive workload during walking (p<.05). Performance measures (e.g., cadence) only changed under high cognitive workload. As a result, psychophysiological measures are the most sensitive to identify changes in cognitive workload during walking. These parameters reflect the cognitive effort necessary to maintain performance during complex walking and can easily be assessed regardless of the task. This makes them excellent candidates to feed to the control loop of a biocooperative prosthesis in order to detect the cognitive workload. This information can then be used to adapt the robotic assistance to the patient's cognitive abilities.

Body weight support during robot-assisted walking: influence on the trunk and pelvis kinematics.

BACKGROUND: Efficacy studies concerning robot assisted gait rehabilitation showed limited clinical benefits. A changed kinematic pattern might be responsible for this. Little is known about the kinematics of the trunk and pelvis during robot assisted treadmill walking (RATW). OBJECTIVE: The aim of this study was to assess the trunk and pelvis kinematics of healthy subjects during RATW, with different amounts of body weight support (BWS) compared to regular treadmill walking (TW). METHOD: Eighteen healthy participants walked on a treadmill, while kinematics were registered by an electromagnetic tracking device. Hereafter, the kinematics of pelvis and trunk were registered during RATW (guidance force 30%) with 0%, 30% and 50% BWS. RESULTS: Compared to TW, RATW showed a decrease in the following trunk movements: axial rotation, anteroposterior flexion, lateral and anteroposterior translation. Besides, a decrease in lateral tilting and all translation of the pelvis was found when comparing RATW with TW. Furthermore, the anteroposterior tilting of the pelvis increased during RATW. CONCLUSION: In general, there was a decrease in trunk and pelvis movement amplitude during RATW compared with regular TW. Though, it is not known if these changes are responsible for the limited efficacy of robot assisted gait rehabilitation. Further research is indicated.

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

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.

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-κß 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.

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.

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 ß activity across the whole brain. Postexercise AR and PR elicited no significant electrocortical differences, whereas CWI induced significantly increased ß3 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 ß activity, hence representing decreased arousal. Postexercise CWI increased ß3 activity at BA 13 and 40, brain areas involved in somatosensory information processing.

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.

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.