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The present study sought to replicate two non-intuitive effects reported in the literature on lateral manual interception of uniformly moving targets, the angle-of-approach (AoA) effect and the reversal-movement (RM) effect. Both entail an influence of the target trajectory's incidence angle on the observed interceptive hand movements along the interception axis; they differ in the interception location considered. The AoA effect concerns all trajectory conditions requiring hand movement to allow successful interception, while the RM effect concerns the particular condition where the target will in fact arrive at the hand's initial position and no hand movement is therefore required but nevertheless regularly produced. Whereas the AoA effect has been systematically replicated, the RM effect has not. To determine whether the RM effect is in fact a reproducible phenomenon, we deployed a procedure enhancing the uncertainty about the target's future arrival locations with respect to the hand's initial position and included low-to-high target motion speeds. Results demonstrated the presence of both the AoA effect and the RM effect. The AoA effect was observed for all relevant interception locations, with the effect being stronger for the farther interception locations and the lower target speeds. The RM effect, with the hand first moving away from its initial position, in the direction of the target, before reversing direction, was observed in a higher proportion of trials for target trajectories with larger incidence angles and lower speeds. Earlier initiation gave rise to reversal movements of larger amplitude. Both effects point to visual guidance of hand movement partially based in reliance on information with respect to current lateral ball position. We conclude that the information used in lateral manual interception is of an intermediate order, which can be conceived as resulting from a partial combination of target position and velocity information or information in the form of a fractional order derivative., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Ledouit, Borooghani, Casanova, Benguigui, Zaal and Bootsma.)

Purpose: To analyze and compare the physiological responses of women during singles and doubles beach tennis sessions., Methods: In this crossover trial, twenty-two women with previous participation in amateur beach tennis tournaments randomly performed two experimental sessions: singles and doubles beach tennis. The routine for both sessions consisted of 10-min of seated rest, followed by 45-min of beach tennis and 30-min of post-exercise recovery. Participants were matched against opponents of the same competition level, defined according to their local beach tennis ranking (advanced or intermediate level). They warmed up with basic techniques for 5-min and played 3 matches lasting 12-min, interspersed with 2-min recovery intervals. Heart rate (HR), energy expenditure (EE), number of steps (STEPS), handgrip strength (HS), rating of perceived exertion (RPE), and enjoyment were assessed throughout the sessions. Generalized estimating equations were employed to examine the main effects between experimental sessions over the time and in relation to competition level., Results: HRmean and HRmax (Δ: HRmean = 13 ± 3 bpm; HRmax = 11 ± 3 bpm) as well as EE and Steps (Δ: EE = 66 ± 22 kcal; RPE = 2 ± 0 A.U.; Steps = 250 ± 52 A.U.) were higher in singles than doubles ( p < 0.05). The percentage of total time spent in the highest HR zone (91-100%HRmax) was significantly greater in singles than in doubles (39% ± 22% vs. 15% ± 18%; p < 0.05). Differences were found in the percentage of total time spent in each HR zone, recovery HR, and HS between competition levels ( p < 0.05)., Conclusion: Singles beach tennis resulted in higher physiological demands than doubles in women, and players' competition level partly affects the training responses., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Jung, Carpes, Domingues, Abreu, Mohr and Ferrari.)

Background: Unstable gait leading to falls negatively impacts the quality of life in many people with Parkinson's disease (PD). Systematic review evidence provides moderate to strong evidence of efficacy for a wide range of physiotherapy-based interventions to reduce gait impairment. However, outcomes have often focused on gait assessments conducted in controlled laboratory or clinical environments., Objective: This perspective investigates the complexities and challenges of conducting real-world gait assessments in people with PD and the factors that may influence the translation from improved lab-assessed gait to improved real-world gait., Methods: Through a thorough review of current literature, we present an in-depth analysis of current methodological approaches to real-world gait assessments and the challenges that may influence the translation of an intervention's success from lab-based outcomes to improved walking during daily life., Results: We identified six key factors that may influence the translation of intervention success into real-world environments at different stages of the process. These factors comprise the gait intervention, parameters analyzed, sensor setup, assessment protocols, characteristics of walking bouts, and medication status. We provide recommendations for each factor based on our synthesis of current literature., Conclusion: This perspective emphasizes the importance of measuring intervention success outside of the laboratory environment using real-world gait assessments. Our findings support the need for future studies to bridge the gap between proven efficacy for gait as assessed in controlled laboratory environments and real-world impact for people with PD., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Lang, van Dieen, Brodie, Welzel, Maetzler, Singh and Ravi.)

The relationship between a performer's conscious involvement or investment in movement control and monitoring and the ability to inhibit the movement is still unclear. We conducted three experiments to investigate whether a higher inclination for conscious movement investment benefits the inhibition of a simple keypress response. In all experiments, the inclination for conscious movement investment was measured with the Movement-Specific Reinvestment Scale. In Experiment 1, participants performed the go/no-go task and conscious investment was manipulated by directing conscious attention either to the finger movement (i.e., internal focus) or to the resulting motion of the key (i.e., external focus). The results showed that neither the participants' inclination for conscious movement investment, nor the direction of conscious attention affected inhibition performance. In Experiment 2, participants performed the stop-signal task, which is more attention demanding than the go/no-go task. The results showed that participants with a high or low inclination for conscious movement investment did not differ in inhibition performance. In Experiment 3 an ego-depletion procedure was included that limits resources for conscious movement investment. Before and after this ego-depletion procedure, participants performed the stop-signal task. The results showed that participants with a high inclination for conscious movement investment slowed down inhibition when they felt mentally depleted, while no slowing down of inhibition was found among participants who felt less depleted and/or had a low inclination for conscious movement investment. Together, the study provides evidence that increased conscious movement investment is beneficial for movement inhibition. Yet, these effects only emerge against the dynamic background of interacting individual (e.g., inclination for conscious movement investment, available attentional resources) and task constraints (e.g., task difficulty)., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 You, Weng, Suprianto and van der Kamp.)

Introduction: Facial expressions conveying an emotion may affect social interactions, such as approach- or avoidance-related behaviors. A specific facial feature is the gaze direction. An emotional facial expression such as anger will elicit distinct behavioral tendencies, depending on whether the angry gaze is directed toward the onlooker, or in a different direction. We tested whether facial expressions of anger and fear, combined with direct or averted gaze, elicit approach- or avoidance tendencies, using a go/no-go variant of the whole-body stepping task., Method: Healthy adults stood on a force plate, recording the center of pressure (COP). Participants were presented with angry or fearful faces; either with direct or averted gaze. Participants had to identify the emotion, and "depending on instructions- either make a single step forward, or remain in a quiet stance. From the COP of the forward steps, we derived parameters such as reaction time and step size. From the quiet standing trials we derived parameters of postural sway, indicative of postural "freeze." We used analysis of variance to analyze the outcomes., Results and Discussion: First, we found that steps were initiated faster with angry faces than with fearful faces, in line with existing literature. Second, we did not observe a significant effect of gaze direction. Forward steps with direct and averted gaze had similar COP characteristics. Finally, we had expected to find freeze (postural immobility) with fearful faces, but this was also not observed. We discuss various explanations for the finding, and implications for research into the motoric grounding of social interactions., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Lebert, Vilarroya and Stins.)

Whole-body vibration (WBV) therapy is a way of passive exercise in which subjects are exposed to mild and well-controlled mechanical vibrations through a vibrating platform. For a long time, studies have focused on the effects and applications of WBV to enhance musculoskeletal performance in athletes and patients suffering from musculoskeletal disorders. Recent evidence points toward the positive effect of WBV on the brain and its therapeutic potential in brain disorders. Research being done in the field gradually reveals cellular and molecular mechanisms underlying WBV affecting the body and brain. Particularly, the influence of WBV on immune and brain function is a growing field that warrants an up-to-date and integrated review. Immune function is closely intertwined with brain functioning and plays a significant role in various brain disorders. Dysregulation of the immune response is linked to conditions such as neuroinflammation, neurodegenerative diseases, and mood disorders, highlighting the crucial connection between the immune system and the brain. This review aims to explore the impact of WBV on the cellular and molecular pathways involved in immune and brain functions. Understanding the effects of WBV at a cellular and molecular level will aid in optimizing WBV protocols to improve its therapeutic potential for brain disorders., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Ahuja, Arauz, van Heuvelen, Kortholt, Oroszi and van der Zee.)

While shoulder injuries resulting from the bench press exercise are commonly reported, no biomechanical evidence for lowering injury risk is currently available. Therefore, the aim of the present study was to compare musculoskeletal shoulder loads and potential injury risk during several bench press variations. Ten experienced strength athletes performed 21 technical variations of the barbell bench press, including variations in grip width of 1,1.5 and 2 bi-acromial widths (BAW), shoulder abduction angles of 45°, 70° and 90°, and scapula poses including neutral, retracted, and released conditions. Motions and forces were recorded by an opto-electronic measurement system and an instrumented barbell. An OpenSim musculoskeletal shoulder model was employed to estimate joint reaction forces in the glenohumeral and acromioclavicular joints. Time-series of joint reaction forces were compared between techniques by statistical non-parametric mapping. Results showed that narrower grip widths of < 1.5 BAW decreased acromioclavicular compression ( p < 0.05), which may decrease the risk for distal clavicular osteolysis. Moreover, scapula retraction, as well as a grip width of < 1.5 BAW ( p < 0.05), decreased glenohumeral posterior shear force components and rotator cuff activity and may decrease the risk for glenohumeral instability and rotator cuff injuries. Furthermore, results showed that mediolaterally exerted barbell force components varied considerably between athletes and largely affected shoulder reaction forces. It can be concluded that the grip width, scapula pose and mediolateral exerted barbell forces during the bench press influence musculoskeletal shoulder loads and the potential injury risk. Results of this study can contribute to safer bench press training guidelines., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Noteboom, Belli, Hoozemans, Seth, Veeger and Van Der Helm.)

In this study, we aimed to characterize the affordance of interceptability for oneself using a manual lateral interception paradigm. We asked a two-fold research question: (1) What makes a virtual ball interceptable or not? (2) How reliably can individuals perceive this affordance for oneself? We hypothesized that a spatiotemporal boundary would determine the interceptability of a ball, and that individuals would be able to perceive this boundary and make accurate perceptual judgments regarding their own interceptability. To test our hypotheses, we administered a manual lateral interception task to 15 subjects. They were first trained on the task, which was followed by two experimental sessions: action and judging . In the former, participants were instructed to intercept as many virtual balls as possible using a hand-held slider to control an on-screen paddle. In the latter session, while making interceptions, participants were instructed to call "no" as soon as they perceived a ball to be uninterceptable. Using generalized linear modeling on the data, we found a handful of factors that best characterized the affordance of interceptability. As hypothesized, distance to be covered and ball flight time shaped the boundary between interceptable and uninterceptable balls. Surprisingly, the angle of approach of the ball also co-determined interceptability. Altogether, these variables characterized the actualized interceptability. Secondly, participants accurately perceived their own ability to intercept balls on over 75% of trials, thus supporting our hypothesis on perceived interceptability. Analyses revealed that participants considered this action boundary while making their perceptual judgments. Our results imply that the perceiving and actualizing of interceptability are characterized by a combination of the same set of variables., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Damle, Bootsma and Zaal.)

Background: Exergaming has the potential to increase adherence to exercise through play, individually tailored training, and (online) remote monitoring. Reality Digital Therapeutics (Reality DTx ® ) is a digital therapeutic software platform for augmented reality (AR) glasses that enables a home-based gait-and-balance exergaming intervention specifically designed for people with Parkinson's disease (pwPD)., Objective: The primary objective was to evaluate the feasibility and potential efficacy of Reality DTx ® AR exergaming intervention for improving gait, balance, and walking-adaptability fall-risk indicators. The secondary objective was to evaluate the potential superiority of AR glasses [Magic Leap 2 (ML2) vs. HoloLens 2 (HL2)]., Methods: This waitlist-controlled clinical feasibility study comprised three laboratory visits (baseline; pre-intervention; and post-intervention), a home visit, and a 6-week AR exergaming intervention. Five complementary gait-and-balance exergames were remotely prescribed (default five sessions/week of 30 active minutes/session), monitored, and tailored. Feasibility was assessed in terms of safety, adherence, and user experience. During laboratory visits, gait-and-balance capacity was assessed using standard clinical gait-and-balance tests and advanced walking-adaptability fall-risk assessments., Results: In total, 24 pwPD participated. No falls and four near falls were reported. Session adherence was 104%. The User Experience Questionnaire scores for Reality DTx ® ranged from above average to excellent, with superior scores for HL2 over ML2 for Perspicuity and Dependability. Intervention effects were observed for the Timed Up and Go test (albeit small), the Five Times Sit to Stand test, and walking speed. Walking-adaptability fall-risk indicators all improved post-intervention., Conclusion: Reality DTx ® is a safe, adherable, usable, well-accepted, and potentially effective intervention in pwPD. These promising results warrant future randomized controlled trials on the (cost-)effectiveness of home-based AR exergaming interventions for improving gait, balance, and fall risk., Clinical Trial Registration: ClinicalTrials.gov, identifier NCT05605249., Competing Interests: This study was part of a collaboration between Vrije Universiteit Amsterdam and Strolll Limited, the manufacturer of Reality DTx®, which was formalized in a consortium agreement associated with their joint EUreka Eurostars grant. The Vrije Universiteit Amsterdam transferred IP related to AR cueing and data science to Strolll Limited in return for share options. MR is scientific advisor for Strolll Limited ancillary to his full-time position as Associate Professor Technology in Motion at the Vrije Universiteit Amsterdam. Anonymized information on technical issues, adherence, usability and exergame performance obtained in this study were shared with Strolll Limited for further development of Reality DTx®., (Copyright © 2024 Hardeman, Geerse, Hoogendoorn, Nonnekes and Roerdink.)

Introduction: External cueing can improve gait in people with Parkinson's disease (PD), but there is a need for wearable, personalized and flexible cueing techniques that can exploit the power of action-relevant visual cues. Augmented Reality (AR) involving headsets or glasses represents a promising technology in those regards. This study examines the gait-modifying effects of real-world and AR cueing in people with PD., Methods: 21 people with PD performed walking tasks augmented with either real-world or AR cues, imposing changes in gait speed, step length, crossing step length, and step height. Two different AR headsets, differing in AR field of view (AR-FOV) size, were used to evaluate potential AR-FOV-size effects on the gait-modifying effects of AR cues as well as on the head orientation required for interacting with them., Results: Participants modified their gait speed, step length, and crossing step length significantly to changes in both real-world and AR cues, with step lengths also being statistically equivalent to those imposed. Due to technical issues, step-height modulation could not be analyzed. AR-FOV size had no significant effect on gait modifications, although small differences in head orientation were observed when interacting with nearby objects between AR headsets., Conclusion: People with PD can modify their gait to AR cues as effectively as to real-world cues with state-of-the-art AR headsets, for which AR-FOV size is no longer a limiting factor. Future studies are warranted to explore the merit of a library of cue modalities and individually-tailored AR cueing for facilitating gait in real-world environments., Competing Interests: This research project was a collaborative effort between Vrije Universiteit Amsterdam and Strolll Limited, the manufacturer of the purpose-specific AR cueing application. The collaboration was formalized through a consortium agreement linked to their joint EUreka Eurostars grant. As part of the arrangement, Vrije Universiteit Amsterdam transferred intellectual property related to AR cueing and data science to Strolll Limited in exchange for share options. Additionally, MR serves as a scientific advisor for Strolll Limited alongside his full-time position as Associate Professor of Technology in Motion at Vrije Universiteit Amsterdam. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Hoogendoorn, Geerse, van Dam, Stins, and Roerdink.)

Introduction: The concept of affordance refers to the opportunities for action provided by the environment, often conveyed through visual information. It has been applied to explain visuomotor processing and movement planning. As emotion modulates both visual perception and the motor system, it is reasonable to ask whether emotion can influence affordance judgments. If present, this relationship can have important ontological implications for affordances. Thus, we investigated whether the emotional value of manipulable objects affected the judgment of the appropriate grasping that could be used to interact with them (i.e., their affordance)., Methods: Volunteers were instructed to use a numerical scale to report their judgment on how an observed object should be grasped. We compared these judgments across emotional categories of objects (pleasant, unpleasant and neutral), while also considering the expected effect of object size., Results: We found that unpleasant objects were rated as more appropriately graspable by a precision grip than pleasant and neutral objects. Simultaneously, smaller object size also favored this judgment. This effect was seen in all emotional categories examined in equal magnitude., Discussion: Our findings suggest that the emotional value of objects modulates affordance judgments in a way that favors careful manipulation and minimal physical contact with aversive stimuli. Finally, we discuss how this affective aspect of our experience of objects overlaps with what affordances are conceptualized to be, calling for further reexamination of the relationship between affordances and emotions., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Felippin, Azevedo, Saunier, Keniston and Nogueira-Campos.)

The IntelliCage (IC) permits the assessment of the behavior and learning abilities of mice in a social home cage context. To overcome water deprivation as an aversive driver of learning, we developed protocols in which spatial learning is motivated appetitively by the preference of mice for sweetened over plain water. While plain water is available at all times, only correct task responses give access to sweetened water rewards. Under these conditions, C57BL/6J mice successfully mastered a corner preference task with the reversal and also learned a more difficult time-place task with reversal. However, the rate of responding to sweetened water decreased strongly with increasing task difficulty, indicating that learning challenges and reduced success in obtaining rewards decreased the motivation of the animals to seek sweetened water. While C57BL/6J mice of both sexes showed similar initial taste preferences and learned similarly well in simple learning tasks, the rate of responding to sweetened water and performance dropped more rapidly in male than in female mice in response to increasing learning challenges. Taken together, our data indicate that male mice can have a disadvantage relative to females in mastering difficult, appetitively motivated learning tasks, likely due to sex differences in value-based decision-making., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Nigri, Bramati, Steiner and Wolfer.)

Previous research found that when participants across the lifespan could be the architect of their own stepping-stones landscapes, they create nonstandardized configurations with gap-width variation. Yet, architects often use standardized dimensions in their designs for playgrounds and outdoor fitness areas. To scrutinize why architects tend to seek for more standardized designs than the examined target users, we tested the hypothesis that the difference is caused by a different perspective during the making process. After all, landscape architects generally design on 2D maps, while the participants designed in situ. We asked 67 participants to design a stepping-stones landscape on a 2D map and 67 other participants to create the landscape in situ. Contrary to our expectations, we found no indications that designing on a 2D map leads to more standardized configurations. We end with discussing other characteristics of the design processes that could potentially explain the omnipresent standardization in design., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Jeschke, Caljouw, Zaal and Withagen.)

Introduction: Hand opening is reduced by abnormal wrist and finger flexor activity in many individuals with stroke. This flexor activity also limits hand opening produced by functional electrical stimulation (FES) of finger and wrist extensor muscles. Recent advances in electrical nerve block technologies have the potential to mitigate this abnormal flexor behavior, but the actual impact of nerve block on hand opening in stroke has not yet been investigated., Methods: In this study, we applied the local anesthetic ropivacaine to the median and ulnar nerve to induce a complete motor block in 9 individuals with stroke and observed the impact of this block on hand opening as measured by hand pentagonal area. Volitional hand opening and FES -driven hand opening were measured, both while the arm was fully supported on a haptic table ( Unloaded ) and while lifting against gravity ( Loaded ). Linear mixed effect regression (LMER) modeling was used to determine the effect of Block ., Results: The ropivacaine block allowed increased hand opening, both volitional and FES-driven, and for both unloaded and loaded conditions. Notably, only the FES -driven and Loaded condition's improvement in hand opening with the block was statistically significant. Hand opening in the FES and Loaded condition improved following nerve block by nearly 20%., Conclusion: Our results suggest that many individuals with stroke would see improved hand-opening with wrist and finger flexor activity curtailed by nerve block, especially when FES is used to drive the typically paretic finger and wrist extensor muscles. Such a nerve block (potentially produced by aforementioned emerging electrical nerve block technologies) could thus significantly address prior observed shortcomings of FES interventions for individuals with stroke., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author declares that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Dewald, Yao, Dewald, Nader and Kirsch.)

Performance in stair-climbing is largely associated with disruptions to mobility and community participation in children with cerebral palsy (CP). It is important to understand the nature of motor impairments responsible for making stairs a challenge in children with bilateral CP to clarify underlying causes of impaired mobility. In pediatric clinical populations, sensitive measurements of movement quality can be captured during the initial step of stair ascent. Thus, the purpose of this study was to quantify the lower limb joint moments of children with bilateral CP during the stance phases of a step-up task. Participants performed multiple stepping trials in a university gait laboratory. Outcome measures included extensor support moments (the sum of hip, knee, and ankle sagittal plane moments), hip abduction moments, and their timing. We recruited seven participants per group. We found that peak support and hip abduction moments were similar in the bilateral CP group compared to the typical development (TD) group. We also found that children with bilateral CP timed their peak moments closer together and increasingly depended on the hip joint to complete the task, especially in their more affected (MA) lower limb. Our investigation highlights some underlying causes that may make stair climbing a challenge for the CP population, including a loss of selective voluntary motor control (SVMC), and provides a possible treatment approach to strengthen lower limb muscles., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Goyal, Gordon and Sukal-Moulton.)

The IntelliCage allows automated testing of cognitive abilities of mice in a social home cage environment without handling by human experimenters. Restricted water access in combination with protocols in which only correct responses give access to water is a reliable learning motivator for hippocampus-dependent tasks assessing spatial memory and executive function. However, water restriction may negatively impact on animal welfare, especially in poor learners. To better comply with the 3R principles, we previously tested protocols in which water was freely available but additional access to sweetened water could be obtained by learning a task rule. While this purely appetitive motivation worked for simple tasks, too many mice lost interest in the sweet reward during more difficult hippocampus-dependent tasks. In the present study, we tested a battery of increasingly difficult spatial tasks in which water was still available without learning the task rule, but rendered less attractive either by adding bitter tasting quinine or by increasing the amount of work to obtain it. As in previous protocols, learning of the task rule provided access to water sweetened with saccharin. The two approaches of dual motivation were tested in two cohorts of female C57BL/6 N mice. Compared to purely appetitive motivation, both novel protocols strongly improved task engagement and increased task performance. Importantly, neither of the added disincentives had an adverse impact on liquid consumption, health status or body weight of the animals. Our results show that it is possible to refine test protocols in the IntelliCage so that they challenge cognitive functions without restricting access to water., Competing Interests: DW was involved in the development of the IntelliCage system. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Ma, Schildknecht, Steiner, Amrein, Nigri, Bramati and Wolfer.)

Introduction: Hypophonia is a common feature of Parkinson's disease (PD); however, the contribution of motor cortical activity to reduced phonatory scaling in PD is still not clear., Methods: In this study, we employed a sustained vowel production task during functional magnetic resonance imaging to compare brain activity between individuals with PD and hypophonia and an older healthy control (OHC) group., Results: When comparing vowel production versus rest, the PD group showed fewer regions with significant BOLD activity compared to OHCs. Within the motor cortices, both OHC and PD groups showed bilateral activation of the laryngeal/phonatory area (LPA) of the primary motor cortex as well as activation of the supplementary motor area. The OHC group also recruited additional activity in the bilateral trunk motor area and right dorsal premotor cortex (PMd). A voxel-wise comparison of PD and HC groups showed that activity in right PMd was significantly lower in the PD group compared to OHC (p < 0.001, uncorrected). Right PMd activity was positively correlated with maximum phonation time in the PD group and negatively correlated with perceptual severity ratings of loudness and pitch., Discussion: Our findings suggest that hypoactivation of PMd may be associated with abnormal phonatory control in PD., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Manes, Kurani, Herschel, Roberts, Tjaden, Parrish and Corcos.)

Introduction: Previous studies found that post-stroke motor impairments are associated with damage to the lesioned corticospinal tract (CST) and hyperexcitability of the contralesional cortico-reticulospinal tract (CRST). This proof-of-concept study aims to develop a non-invasive brain stimulation protocol that facilitates the lesioned CST and inhibits the contralesional CRST to improve upper extremity rehabilitation in individuals with moderate-to-severe motor impairments post-stroke., Methods: Fourteen individuals (minimum 3 months post ischemic stroke) consented. Physician decision of the participants baseline assessment qualified eight to continue in a randomized, double-blind cross-over pilot trial (ClinicalTrials.gov Identifier: NCT05174949) with: (1) anodal high-definition transcranial direct stimulation (HD-tDCS) over the ipsilesional primary motor cortex (M1), (2) cathodal HD-tDCS over contralesional dorsal premotor cortex (PMd), (3) sham stimulation, with a two-week washout period in-between. Subject-specific MR images and computer simulation were used to guide HD-tDCS and verified by Transcranial Magnetic Stimulation (TMS) induced Motor Evoked Potential (MEP). The motor behavior outcome was evaluated by an Fugl-Meyer Upper Extremity score (primary outcome measure) and the excitability of the ipslesoinal CST and contralesional CRST was determined by the change of MEP latencies and amplitude (secondary outcome measures)., Results: The baseline ipsilesional M1 MEP latency and amplitude were correlated with FM-UE. FM-UE scores were improved post HD-tDCS, in comparison to sham stimulation. Both anodal and cathodal HD-tDCS reduced the latency of the ipsilesional M1 MEP. The contralesional PMd MEP disappeared/delayed after HD-tDCS., Discussion: These results suggest that HD-tDCS could improve the function of the lesioned corticospinal tract and reduce the excitability of the contralesional cortico-reticulospinal tract, thus, improving motor function of the upper extremity in more severely impaired individuals., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2023 Williamson, James, He, Li, Sidorov and Yang.)

Background: Antiparkinson medication and subthalamic nucleus deep brain stimulation (STN-DBS), two common treatments of Parkinson's disease (PD), effectively improve skeletomotor movements. However, evidence suggests that these treatments may have differential effects on eye and limb movements, although both movement types are controlled through the parallel basal ganglia loops., Objective: Using a task that requires both eye and upper limb movements, we aimed to determine the effects of medication and STN-DBS on eye and upper limb movement performance., Methods: Participants performed a visually-guided reaching task. We collected eye and upper limb movement data from participants with PD who were tested both OFF and ON medication ( n = 34) or both OFF and ON bilateral STN-DBS while OFF medication ( n = 11). We also collected data from older adult healthy controls ( n = 14)., Results: We found that medication increased saccade latency, while having no effect on reach reaction time (RT). Medication significantly decreased saccade peak velocity, while increasing reach peak velocity. We also found that bilateral STN-DBS significantly decreased saccade latency while having no effect on reach RT, and increased saccade and reach peak velocity. Finally, we found that there was a positive relationship between saccade latency and reach RT, which was unaffected by either treatment., Conclusion: These findings show that medication worsens saccade performance and benefits reaching performance, while STN-DBS benefits both saccade and reaching performance. We explore what the differential beneficial and detrimental effects on eye and limb movements suggest about the potential physiological changes occurring due to treatment., Competing Interests: GP received grant support from National Institute of Neurological Disorders and Stroke, and consulting fees from Guidepoint, Kyowa Kirin. LV receives research support from NIH; receives research support, is on the advisory board of, and consults for Abbott, AbbVie, and Avion; receives research support from and consults for Boston Scientific; receives research support from and is on the advisory board for Biogen; and receives research support from Medtronic, Neuroderm, and Prilenia Therapeutics. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Munoz, Arora, Rivera, Drane, Pal, Verhagen Metman, Sani, Rosenow, Goelz, Corcos and David.)

Background and Aim: Advances in computing technology enabled researchers and clinicians to exploit technological devices for cognitive training and rehabilitation interventions. This expert review aims to describe the available software and device used for cognitive training or rehabilitation interventions of patients with neurological disorders., Methods: A scoping review was carried out to analyze commercial devices/software for computerized cognitive training (CCT) in terms of feasibility and efficacy in both clinical and home settings. Several cognitive domains responding to the different patients' needs are covered., Results: This review showed that cognitive training for patients with neurological diseases is largely covered by several devices that are widely used and validated in the hospital setting but with few translations to remote/home applications. It has been demonstrated that technology and software-based devices are potential and valuable tools to administer remotely cognitive rehabilitation with accessible costs., Conclusion: According to our results, CCT entails the possibility to continue cognitive training also in different settings, such as home, which is a significant breakthrough for the improvement of community care. Other possible areas of use should be the increase in the amount of cognitive therapy in the free time during the hospital stay., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer MA declared a shared affiliation with the author GA to the handling editor at the time of review., (Copyright © 2023 Maggio, De Bartolo, Calabrò, Ciancarelli, Cerasa, Tonin, Di Iulio, Paolucci, Antonucci, Morone and Iosa.)

Introduction: Whether high-intensity interval training (HIIT) can improve lean mass, strength, and power of the lower limbs in young and older people is still under discussion. This study aimed to determine the effect of HIIT on lean mass, maximal strength, rate of force development (RFD), and muscle power of both lower limbs in healthy young and older adults. Secondarily, to compare the effects of HIIT between dominant vs. non-dominant lower limbs of each group. Materials and methods: Healthy older ( n = 9; 66 ± 6 years; BMI 27.1 ± 3.1 kg m -2 ) and young ( n = 9; 21 ± 1 years; BMI 26.2 ± 2.8 kg m -2 ) men underwent 12 weeks of HIIT (3x/week) on a stationary bicycle. The evaluations were made before and after the HIIT program by dual energy X-ray absorptiometry (DEXA), anthropometry, force transducer and, Sit-to-Stand test. The outcomes analyzed were limb lean mass, thigh circumference, maximal voluntary isometric strength, RFD (Time intervals: 0-50, 50-100, 100-200, and 0-200 ms), and muscle power in both lower limbs. Results: After 12 weeks of HIIT, non-dominant limb (NDL) showed increase in limb lean mass ( p < 0.05) but without interaction (time*group). HIIT showed a gain in absolute maximal strength and also when adjusted for thigh circumference in the dominant lower limb (DL) in both groups. The RFD 0-200 ms showed differences between groups but without interaction. The RFD 0-50 ms of the NDL showed post-training improvements ( p < 0.05) in both groups. Only the older group showed differences between DL vs. NDL in most of the RFD obtained post-intervention. In addition, post-HIIT muscle power gain was observed in both groups ( p < 0.05), but mainly in older adults. Conclusion: HIIT promotes increases in lean mass, maximal strength, early RFD, and lower limb muscle power in healthy older and young individuals. The differences shown between the DL and the NDL must be analyzed in future studies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Caparrós-Manosalva, Garrido-Muñoz, Alvear-Constanzo, Sanzana-Laurié, Artigas-Arias, Alegría-Molina, Vidal-Seguel, Espinoza-Araneda, Huard, Pagnussat, Sapunar, Salazar and Marzuca-Nassr.)

Introduction: Hereditary spastic paraplegias (HSPs) are a heterogeneous group of neurodegenerative diseases in which little is known about the most appropriate clinical outcome assessments (COAs) to capture disease progression. The objective of this study was to prospectively determine disease progression after 4.5 years of follow-up with different clinician-reported (ClinRO) and gait performance outcomes (PerFOs)., Methods: Twenty-six HSP patients (15 SPG4, 5 SPG7, 4 SPG5, 2 SPG3A) participated in this single-center cohort study in which the ClinRO: Spastic Paraplegia Rating Scale; and the PerFOs: 10-meters walking test and timed-up and go (TUG), at self-selected and maximal walking speeds; Locomotor Rehabilitation Index; and 6-min walking test were performed at baseline and after 1.5 (18 patients) and 4.5 (13 patients) years., Results: In the 3-year interval between the second and third assessments, significant progressions were only found in PerFOs, while in the overall 4.5 years of follow-up, both PerFOs and ClinROs presented significant progressions. The progression slopes of COAs modeled according to the disease duration allowed the estimation of the annual progression of the outcomes and sample size estimations for future clinical trials of interventions with different effect sizes. TUG at maximal walking speed was the only COA capable of differentiating subjects with a worse compared to a stable/better impression of change and would require the smallest sample size if chosen as the primary endpoint of a clinical trial., Discussion: These findings indicate that both performance and clinician-reported outcomes can capture long-term progression of HSPs, with some PerFOs presenting greater sensitivity to change. The presented data are paramount for planning future disease-modifying and symptomatic therapy trials for this currently untreatable group of diseases., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Cubillos Arcila, Dariva Machado, Martins, Leotti, Schüle, Peyré-Tartaruga and Saute.)

Background: Exergames provide a promising new approach to implement simultaneous motor-cognitive training, which may support preventing the decline in cognitive functioning in older adults who have a mild neurocognitive disorder (mNCD)., Objectives: To evaluate feasibility, system usability, and acceptance of "Brain-IT", a newly developed training concept combining exergame-based motor-cognitive training and heart rate variability (HRV) guided resonance breathing for the secondary prevention of mNCD., Methods: A pilot randomized controlled trial (RCT) with an allocation ratio of 2:1 (i.e., intervention:control) was conducted. The control group proceeded with usual care. The intervention group performed a 12-week training according to the "Brain-IT" training concept implemented with the "Senso Flex" (Dividat AG) exergaming system in addition to usual care. Feasibility and usability outcomes were analyzed using descriptive statistics. User acceptance was analyzed qualitatively and using Friedman analysis of variance (ANOVA), as well as Wilcoxon signed-rank tests., Results: Eighteen participants (77.3 ± 9.8 years; 44.4% females) were included. On average, we recruited 2.2 participants per month, and 35.3% of the individuals contacted were included. The intervention group had an attrition rate of 20% and mean adherence and compliance rates of 85.0 and 84.1%, respectively. The mean system usability score, measured with the system usability scale, was 71.7. High levels of exergame enjoyment, an increase in exergame enjoyment, and internalization of training motivation with large effect sizes ( p = 0.03, r = 0.75 and p = 0.03, r = 0.74, respectively), as well as acceptable perceived usefulness, were observed. Preliminary data on the effects of the "Brain-IT" training are promising., Conclusion: The feasibility and usability of the "Brain-IT" training are acceptable. However, frequent occurrences of technical problems and difficulties in using the exergame training system were identified as barriers to performing the "Brain-IT" training. To optimize feasibility, either improvements or alternative solutions are required in the hardware and software of the exergame used to implement the "Brain-IT" training. The "Brain-IT" training itself was well-accepted by older adults who have mNCD. Therefore, the effectiveness of the "Brain-IT" training concept should be investigated in future studies., Trial Registration: clinicaltrials.gov/ct2/show/NCT04996654., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Manser, Poikonen and de Bruin.)

Parkinson's Disease (PD) is a prevalent and complex age-related neurodegenerative condition for which there are no disease-modifying treatments currently available. The pathophysiological process underlying PD remains incompletely understood but increasing evidence points to multiple system dysfunction. Interestingly, the past decade has produced evidence that exercise not only reduces signs and symptoms of PD but is also potentially neuroprotective. Characterizing the mechanistic pathways that are triggered by exercise and lead to positive outcomes will improve understanding of how to counter disease progression and symptomatology. In this review, we highlight how exercise regulates the neuroendocrine system, whose primary role is to respond to stress, maintain homeostasis and improve resilience to aging. We focus on a group of hormones - cortisol, melatonin, insulin, klotho, and vitamin D - that have been shown to associate with various non-motor symptoms of PD, such as mood, cognition, and sleep/circadian rhythm disorder. These hormones may represent important biomarkers to track in clinical trials evaluating effects of exercise in PD with the aim of providing evidence that patients can exert some behavioral-induced control over their disease., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Luthra, Christou, Clow and Corcos.)

The present study strived to gain a more profound understanding of the distinctions in development between swimmers who are considered to be on track to the senior elite level compared to those who are not. Longitudinal data of 29 talented sprint and middle-distance swimmers (12 males; 17 females) on season best performances (season best times) and underlying performance characteristics (anthropometrics, starts, turns, maximal swimming velocity, stroke index [SI, an indirect measure of swimming efficiency] and lower body power) were collected over four swimming seasons (median of n = 3 seasons per swimmer). Based on their season best performance at early senior age (males aged 18-19; females aged 17-18), some swimmers were considered to be on track to reach the elite level (referred to as high-performing seniors; 6 males and 10 females), whereas others were not (referred to as lower-performing seniors; 6 males and 7 females). Retrospectively studying these swimmers (males and females separately), we found that all high-performing seniors were already on track to the elite level at late junior age (males aged 17; females aged 16), evidenced with faster season best performances throughout their transition compared to their lower-performing peers ( p < 0.05). Independent sample t -tests revealed that high-performing seniors significantly outscored their lower-performing peers on maximal swimming velocity (males and females), starts and turns (males), SI (females) and lower body power (females) at late junior age ( p < 0.05). Additionally, multilevel models showed faster rates of development for high-performing seniors on turns and maximal swimming velocity (males), and SI (females) compared to lower-performing peers during the junior-to-senior transition ( p < 0.05). Particularly, the higher initial levels of swim performance and underlying characteristics at late junior age as well as the ability to keep progressing on season best performances (males and females), turns and maximal swimming velocity (males), and SI (females) during the junior-to-senior transition, may be crucial factors in the attainment of swimming expertise., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Post, Koning, Visscher and Elferink-Gemser.)

Introduction: It is suggested that eye movement recordings could be used as an objective evaluation method of motor imagery (MI) engagement. Our investigation aimed to evaluate MI engagement in patients after stroke (PaS) compared with physical execution (PE) of a clinically relevant unilateral upper limb movement task of the patients' affected body side., Methods: In total, 21 PaS fulfilled the MI ability evaluation [Kinaesthetic and Visual Imagery Questionnaire (KVIQ-10), body rotation task (BRT), and mental chronometry task (MC)]. During the experiment, PaS moved a cup to distinct fields while wearing smart eyeglasses (SE) with electrooculography electrodes integrated into the nose pads and electrodes for conventional electrooculography (EOG). To verify MI engagement, heart rate (HR) and oxygen saturation (SpO 2 ) were recorded, simultaneously with electroencephalography (EEG). Eye movements were recorded during MI, PE, and rest in two measurement sessions to compare the SE performance between conditions and SE's psychometric properties., Results: MI and PE correlation of SE signals varied between r = 0.12 and r = 0.76. Validity (cross-correlation with EOG signals) was calculated for MI ( r = 0.53) and PE ( r = 0.57). The SE showed moderate test-retest reliability (intraclass correlation coefficient) with r = 0.51 (95% CI 0.26-0.80) for MI and with r = 0.53 (95% CI 0.29 - 0.76) for PE. Event-related desynchronization and event-related synchronization changes of EEG showed a large variability. HR and SpO 2 recordings showed similar values during MI and PE. The linear mixed model to examine HR and SpO 2 between conditions (MI, PE, rest) revealed a significant difference in HR between rest and MI, and between rest and PE but not for SpO 2 . A Pearson correlation between MI ability assessments (KVIQ, BRT, MC) and physiological parameters showed no association between MI ability and HR and SpO 2 ., Conclusion: The objective assessment of MI engagement in PaS remains challenging in clinical settings. However, HR was confirmed as a reliable parameter to assess MI engagement in PaS. Eye movements measured with the SE during MI did not resemble those during PE, which is presumably due to the demanding task. A re-evaluation with task adaptation is suggested., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Gäumann, Aksöz, Behrendt, Wandel, Cappelletti, Krug, Mörder, Bill, Parmar, Gerth, Bonati and Schuster-Amft.)

Stroke is a leading cause of disability worldwide and upper limb hemiparesis is the most common post-stroke disability. Recent studies suggest that clinically significant motor recovery is possible in chronic stroke survivors with severe impairment of the upper limb. Three promising strategies that have been investigated are (1) high dose rehabilitation therapy (2) bilateral motor priming and (3) vagus nerve stimulation. We propose that the future of effective and efficient upper limb rehabilitation will likely require a combination of these approaches., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 King, Pedi, Stoykov, Corcos and Urday.)

Background: There is evidence that ambulatory people with incomplete spinal cord injury (iSCI) have an impaired ability to control lateral motion of their whole-body center of mass (COM) during walking. This impairment is believed to contribute to functional deficits in gait and balance, however that relationship is unclear. Thus, this cross-sectional study examines the relationship between the ability to control lateral COM motion during walking and functional measures of gait and balance in people with iSCI., Methods: We assessed the ability to control lateral COM motion during walking and conducted clinical gait and balance outcome measures on 20 ambulatory adults with chronic iSCI (C1-T10 injury, American Spinal Injury Association Impairment Scale C or D). To assess their ability to control lateral COM motion, participants performed three treadmill walking trials. During each trial, real-time lateral COM position and a target lane were projected on the treadmill. Participants were instructed to keep their lateral COM position within the lane. If successful, an automated control algorithm progressively reduced the lane width, making the task more challenging. If unsuccessful, the lane width increased. The adaptive lane width was designed to challenge each participant's maximum capacity to control lateral COM motion during walking. To quantify control of lateral COM motion, we calculated lateral COM excursion during each gait cycle and then identified the minimum lateral COM excursion occurring during five consecutive gait cycles. Our clinical outcome measures were Berg Balance Scale (BBS), Timed Up and Go test (TUG), 10-Meter Walk Test (10MWT) and Functional Gait Assessment (FGA). We used a Spearman correlation analysis ( ρ ) to examine the relationship between minimum lateral COM excursion and clinical measures., Results: Minimum lateral COM excursion had significant moderate correlations with BBS ( ρ  = -0.54, p  = 0.014), TUG ( ρ  = 0.59, p  = 0.007), FGA ( ρ  = -0.59, p  = 0.007), 10MWT-preferred ( ρ  = -0.59, p  = 0.006) and 10MWT-fast ( ρ  = -0.68, p  = 0.001)., Conclusion: Control of lateral COM motion during walking is associated with a wide range of clinical gait and balance measures in people with iSCI. This finding suggests the ability to control lateral COM motion during walking could be a contributing factor to gait and balance in people with iSCI., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Dusane, Shafer, Ochs, Cornwell, Henderson, Kim and Gordon.)

Fibromyalgia affects skeletal muscles presenting with muscle stiffness, pain, and fatigue. The exercise practice is wellstabilized and suggested for the reduction of symptoms. However, there are some gaps in the literature related to balance and neuromuscular performance in a strength training protocol. The aim of this study is to structure a protocol to verify the effects of strength training applied over a short period, on balance, neuromuscular performance, and fibromyalgia symptoms. Additionally, we intend to analyze the effects of a short period of cessation of training. Participants will be recruited through flyers, internet advertisements, clinical referrals, health professionals, and email outreach. Volunteers will be randomly assigned to the control group or experimental group. Before the training period, symptoms (Fibromyalgia Impact Questionnaire, Visual Analog Scale), balance (force plate), and neuromuscular performance (medicine ball throw and vertical jump) will be assessed. Participants in the experimental group will perform strength training twice a week (50 min each), on alternate days, for 8 weeks (16 sessions). Then, 4 weeks of detraining will be completed. This training program will be carried out online, using real-time videos, and the participants will be divided into two groups with different schedules. The Borg scale will be used to monitor perceived effort in each session. There is a gap in the literature about exercise prescriptions for fibromyalgia. The supervised online intervention enables a wide range of participation. The strength exercises used (without the use of external materials and/or machines) and load (few repetitions per set) represent a novelty to training programming. Moreover, this training program respects the limitations and individuality of the volunteers, providing exercise adaptations. With positive results, the present protocol could be an easy-to-apply guideline with clear instructions on the details related to exercise prescription. Also, ensure the effectiveness of a low-cost and feasible treatment, especially for fibromyalgia patients., Clinical Trial Registration: https://clinicaltrials.gov/, identifier: NCT05646641., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The handling editor PD declared a past collaboration with the author AA., (Copyright © 2023 Albuquerque, Monteiro, Alvarez, Vilarino, Andrade and Neiva.)

Background: Given the demands posed by excessive practice quantities in modern dance, physical and mental health can be compromised. Therefore, there is a need to consider how quality of practice may be improved and possibly even reduce training times. Sports literature has shown that instructions and feedback given by coaches can have an effect on the quality of training and influence self-regulation and the performance of athletes. However, currently little is known about the use of instructions and feedback by dance teachers. The aim of the current study was, therefore, to examine the type of instructions and feedback given by dance teachers during various dance classes., Methods: A total of six dance teachers participated in this study. Video and audio recordings were made of six dance classes and two rehearsals at a contemporary dance university. The dance teacher's coaching behavior was analyzed using the modified Coach Analysis and Intervention System (CAIS). Additionally, feedback and instructions were also examined in terms of their corresponding focus of attention. Absolute numbers, as well as times per minute (TPM) rates were calculated for each behavior before, during, and after an exercise. Absolute numbers were also used to calculate ratios of positive-negative feedback and open-closed questions., Results: Most feedback comments were given after an exercise (472 out of 986 total observed behaviors). Improvisation had the highest positive-negative feedback ratio (29) and open-closed questions ratio (1.56). Out of the focus of attention comments, internal focus of attention comments were used most frequently (572 out of 900)., Discussion/conclusion: The results make clear that there is a large variability in instructions and feedback over teachers and classes. Overall, there is room for improvement toward a higher positive-negative feedback ratio, a higher open-closed question ratio and producing more comments eliciting an external focus of attention., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Soerel, Plaatsman, Kegelaers, Stubbe, van Rijn and Oudejans.)

The laws of physics and mathematics describe the world we live in as internally consistent. As these rules provide a very effective description, and our interaction with the world is also very effective, it seems self-evident that our perception follows these laws. As a result, when trying to explain imperfections in perception, we tend to impose consistency and introduce concepts such as deformations of visual space. In this review, we provide numerous examples that show that in many situations we perceive related attributes to have inconsistent values. We discuss how our tendency to assume consistency leads to erroneous conclusions on how we process sensory information. We propose that perception is not about creating a consistent internal representation of the outside world, but about answering specific questions about the outside world. As the information used to answer a question is specific for that question, this naturally leads to inconsistencies in perception and to an apparent dissociation between some perceptual judgments and related actions., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Smeets and Brenner.)

Introduction: Stepping accuracy, speed, and stability are lower in older compared to young adults. Lower stepping performance in older adults may be due to larger accuracy-speed-stability trade-offs because of reduced ability to simultaneously fulfill these task-level goals. Our goal was to evaluate whether trade-offs are larger in older compared to young adults in a targeted stepping task. Since sensorimotor function declines with age, our secondary goal was to evaluate whether poorer sensorimotor function was associated with larger trade-offs., Methods: Twenty-five young (median 22 years old) and 25 older (median 70 years old) adults stepped into projected targets in conditions with various levels of accuracy, speed, and stability requirements. We determined trade-offs as the change in performance, i.e., foot placement error, step duration, and mediolateral center of pressure path length, between each of these conditions and a control condition. To assess age-related differences in the magnitude of trade-offs, we compared the change in performance between age groups. Associations between trade-offs and measures of sensorimotor function were tested using correlations., Results: We found an accuracy-speed and an accuracy-stability trade-off in both young and older adults, but trade-offs were not different between young and older adults. Inter-subject differences in sensorimotor function could not explain inter-subject differences in trade-offs., Conclusion: Age-related differences in the ability to combine task-level goals do not explain why older adults stepped less accurate and less stable than young adults. However, lower stability combined with an age-independent accuracy-stability trade-off could explain lower accuracy in older adults., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Muijres, Arnalsteen, Daenens, Afschrift and De Groote.)

The ability to flexibly respond and adapt the walking pattern over time to unexpected gait perturbations is pivotal for safe and efficient locomotion. However, these abilities might be affected by age due to age-related changes in sensorimotor functioning. In this cross-sectional lifespan study, we used a split-belt paradigm to determine how age affects the initial response (i.e., flexibility )-and the ability to adapt after prolonged exposure-to a sustained gait perturbation. Healthy adults (N = 75) of different ages (12-13 per decade) were included and walked on a split-belt treadmill, in which a sustained gait perturbation was imposed by increasing one of the belt speeds. Linear regression models, with the evoked spatiotemporal gait asymmetry during the early perturbation and late adaptation, were performed to determine the effects of age on the flexibility and adaptability to split-belt walking. Results showed that the flexibility to respond to an unexpected perturbation decreased across the lifespan, as evidenced by a greater step length asymmetry (SLA) during the early perturbation phase. Despite this reduced flexibility in step lengths, late adaptation levels in SLA were comparable across different ages. With increasing age, however, subjects needed more steps to reach a stable level in SLA. Finally, when the belts were set to symmetrical speeds again, the magnitude of SLA (i.e., the aftereffects ) increased with age. Collectively, these findings suggest that natural ageing comes with a decrease in gait flexibility, while the ability to adapt to split-belt walking was not affected by age-only how adaptation was achieved., (Copyright © 2023 Swart, den Otter and Lamoth.)

Deep brain stimulation (DBS) of the subthalamic nucleus (STN), which consistently improves limb motor functions, shows mixed effects on speech functions in Parkinson's disease (PD). One possible explanation for this discrepancy is that STN neurons may differentially encode speech and limb movement. However, this hypothesis has not yet been tested. We examined how STN is modulated by limb movement and speech by recording 69 single- and multi-unit neuronal clusters in 12 intraoperative PD patients. Our findings indicated: (1) diverse patterns of modulation in neuronal firing rates in STN for speech and limb movement; (2) a higher number of STN neurons were modulated by speech vs. limb movement; (3) an overall increase in neuronal firing rates for speech vs. limb movement; and (4) participants with longer disease duration had higher firing rates. These data provide new insights into the role of STN neurons in speech and limb movement., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Johari, Kelley, Tjaden, Patterson, Rohl, Berger, Corcos and Greenlee.)

Introduction: Children start to run after they master walking. How running develops, however, is largely unknown., Methods: We assessed the maturity of running pattern in two very young, typically developing children in a longitudinal design spanning about three years. Leg and trunk 3D kinematics and electromyography collected in six recording sessions, with more than a hundred strides each, entered our analysis. We recorded walking during the first session (the session of the first independent steps of the two toddlers at the age of 11.9 and 10.6 months) and fast walking or running for the subsequent sessions. More than 100 kinematic and neuromuscular parameters were determined for each session and stride. The equivalent data of five young adults served to define mature running. After dimensionality reduction using principal component analysis, hierarchical cluster analysis based on the average pairwise correlation distance to the adult running cluster served as a measure for maturity of the running pattern., Results: Both children developed running. Yet, in one of them the running pattern did not reach maturity whereas in the other it did. As expected, mature running appeared in later sessions (>13 months after the onset of independent walking). Interestingly, mature running alternated with episodes of immature running within sessions. Our clustering approach separated them., Discussion: An additional analysis of the accompanying muscle synergies revealed that the participant who did not reach mature running had more differences in muscle contraction when compared to adults than the other. One may speculate that this difference in muscle activity may have caused the difference in running pattern., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Bach, Zandvoort, Cappellini, Ivanenko, Lacquaniti, Daffertshofer and Dominici.)

Gender differences in spatial abilities favor males in both childhood and adulthood. During early development, this discrepancy can be attributed, among other things, to the influence of an early testosterone surge in boys, societal stereotypes, and expectations about gender. In the present work, we created a spatial task (including letter rotation and letter mirroring) which used letters as stimuli and evaluated the performance of school-aged children (6-10 years old). During this age period, children are being taught literacy skills which rely on the reorganization of cortical networks and the breakdown of mirror generalization. We divided our sample ( N  = 142, 73 females) into two age groups: 1 st -2 nd (literacy acquisition; N  = 70, 33 females) and 3 rd -5 th (literacy consolidation; N  = 72, 40 females) graders. While boys performed significantly better in letter rotation in the older group, girls' performance remained substandard in both groups. This pattern is reversed for the mirror task, with older girls outperforming their younger counterparts and boys having similar performance in the two groups. Since the age period of our sample is not associated with large variations in the levels of reproductive steroids, we propose that the similarity of performance between younger and older girls in mental rotation of letters could be associated with society's traditional attitudes and expectations on the relationship between visual-spatial skills and gender. As for the mirror task, while only girls had a significant difference between the two age groups, boys did show an improvement, as expected for the inhibition of mirror generalization for letters during reading acquisition., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Resque, de Moura Lobato, da Silva, da Cruz Filho, da Fonseca, de Oliveira Matos and Pereira.)

Efficient movements require intact motor and cognitive function. There is a growing literature on motor-cognitive interventions to improve the overall quality of life of healthy or diseased older people. For such interventions, novel technological advances are crucial not only in terms of motivation but also to improve the user experience in a multi-stimuli world, usually offered as a mixture of real and virtual environments. This article provides a classification system for movement-related research dealing with motor-cognitive interventions performed in different extents of a virtual environment. The classification is divided into three categories: (a) type of digital device with the associated degree of immersiveness provided; (b) presence or absence of a human-computer interaction; and (c) activity engagement during training, defined by activity >1.5 Metabolic Equivalent of task. Since virtual reality (VR) often categorizes different technologies under the same term, we propose a taxonomy of digital devices ranging from computer monitors and projectors to head-mounted VR technology. All immersive technologies that have developed rapidly in recent years are grouped under the umbrella term Extended Reality (XR). These include augmented reality (AR), mixed reality (MR), and VR, as well as all technologies that have yet to be developed. This technology has potential not only for gaming and entertainment, but also for research, motor-cognitive training programs, rehabilitation, telemedicine, etc. This position paper provides definitions, recommendations, and guidelines for future movement-related interventions based on digital devices, human-computer interactions, and physical engagement to use terms more consistently and contribute to a clearer understanding of their implications., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Šlosar, Voelcker-Rehage, Paravlić, Abazovic, de Bruin and Marusic.)

Low back pain (LBP), associated with spine, pelvis, and hip mobility impairments can be caused by tight muscle contractions, to protect sensitized lumbar fasciae. Fascia tissue manipulations are used to treat lumbar fascia in LBP. The effect of fascia tissue manipulations through lumbodorsal skin displacement (SKD) on mobility is inconclusive likely depending on the location and displacement direction of the manipulation. This study aimed to assess whether lumbodorsal SKD affects the flexion -and extension range of motion (ROM), in healthy subjects. Furthermore, we aimed to test the effect of SKD at different locations and directions. Finally, to assess intertester and intratester reliability of SKD. Effects of SKD were tested in a motion capture, single-blinded, longitudinal, experimental study. Sixty-three subjects were randomly assigned to SKD- or sham group. SKD group was subjected to either mediolateral directed SKD during flexion or extension movement, versus a sham. The thoracic, lumbar, and hip angles and finger floor distance were measured to assess the change in ROM. Statistics indicated that the effect size in instantaneously change of flexion -and extension ROM by SKD was large (Effect size: flexion η 2 p = 0.12-0.90; extension η 2 p = 0.29-0.42). No significant effect was present in the sham condition. Flexion ROM decreased whereas the extension ROM increased, depending on SKD location- and displacement direction ( p = 0.70-0.84). Lumbodorsal SKD affects the flexion- and extension spine, pelvis, and hip range of motion. The effects of SKD are direction- and location dependent as well as movement (flexion/extension) specific. Lumbodorsal SKD during flexion and extension may be useful to determine whether or not a patient would benefit from fascia tissue manipulations. Further research is required to obtain insight into the mechanisms 3,k = 0.81-0.93; ICC 3,1 = 0.70-0.84). Lumbodorsal SKD affects the flexion- and extension spine, pelvis, and hip range of motion. The effects of SKD are direction- and location dependent as well as movement (flexion/extension) specific. Lumbodorsal SKD during flexion and extension may be useful to determine whether or not a patient would benefit from fascia tissue manipulations. Further research is required to obtain insight into the mechanisms via which the SKD affects ROM and muscle activation, in healthy, asymptomatic-LBP, and LBP subjects., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 van Amstel, Jaspers and Pool-Goudzwaard.)

The amyloid precursor protein APP plays a crucial role in Alzheimer pathogenesis. Its physiological functions, however, are only beginning to be unraveled. APP belongs to a small gene family, including besides APP the closely related amyloid precursor-like proteins APLP1 and APLP2, that all constitute synaptic adhesion proteins. While APP and APLP2 are ubiquitously expressed, APLP1 is specific for the nervous system. Previous genetic studies, including combined knockouts of several family members, pointed towards a unique role for APLP1, as only APP/APLP1 double knockouts were viable. We now examined brain and neuronal morphology in APLP1 single knockout (KO) animals, that have to date not been studied in detail. Here, we report that APLP1-KO mice show normal spine density in hippocampal CA1 pyramidal cells and subtle alterations in dendritic complexity. Extracellular field recordings revealed normal basal synaptic transmission and no alterations in synaptic plasticity (LTP). Further, behavioral studies revealed in APLP1-KO mice a small deficit in motor function and reduced diurnal locomotor activity, while learning and memory were not affected by the loss of APLP1. In summary, our study indicates that APP family members serve both distinct and overlapping functions that need to be considered for therapeutic treatments of Alzheimer's disease., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Erdinger, Amrein, Back, Ludewig, Korte, von Engelhardt, Wolfer and Müller.)

Background: The interpretation of clinical gait data in children with cerebral palsy (CP) is time-consuming, requires extensive expertise and often lacks transparency. Here we aimed to develop a set of look-up tables to support this process, linking typical gait features as present in CP to their potential underlying impairments., Methods: We developed an initial core set of gait features and their potential underlying impairments based on biomechanical reasoning, literature and clinical experience. This core set was further specified through a Delphi process in a multidisciplinary group of experts in gait analysis of children with CP and evaluated on 20 patient cases. The likelihood of the listed gait feature-impairment relationships was scored by the expert panel on a five-point scale., Results: The final core set included 120 relevant gait feature-impairment relations including likelihood scores. This set was presented in the form of look-up tables in both directions, i.e., sorted by gait features with potential underlying impairment, and sorted by impairments with potential related gait features. The average likelihood score for the relations was 3.5 ± 0.6 (range 2.1-4.6)., Conclusion: The developed set of look-up tables linking gait features and impairments, can assist gait analysts and clinicians in standardized biomechanical reasoning, to support treatment decision-making for gait impairments in children with CP., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 van der Krogt, Houdijk, Wishaupt, van Hutten, Dekker and Buizer.)

Functional magnetic resonance imaging (fMRI) of the human spinal cord (SC) is a unique non-invasive method for characterizing neurovascular responses to stimuli. Group-analysis of SC fMRI data involves co-registration of subject-level data to standard space, which requires manual masking of the cord and may result in bias of group-level SC fMRI results. To test this, we examined variability in SC masks drawn in fMRI data from 21 healthy participants from a completed study mapping responses to sensory stimuli of the C7 dermatome. Masks were drawn on temporal mean functional image by eight raters with varying levels of neuroimaging experience, and the rater from the original study acted as a reference. Spatial agreement between rater and reference masks was measured using the Dice Similarity Coefficient, and the influence of rater and dataset was examined using ANOVA. Each rater's masks were used to register functional data to the PAM50 template. Gray matter-white matter signal contrast of registered functional data was used to evaluate the spatial normalization accuracy across raters. Subject- and group-level analyses of activation during left- and right-sided sensory stimuli were performed for each rater's co-registered data. Agreement with the reference SC mask was associated with both rater (F (7, 140) = 32.12, P < 2 × 10 -16 , η 2 = 0.29) and dataset (F (20, 140) = 20.58, P < 2 × 10 -16 , η 2 = 0.53). Dataset variations may reflect image quality metrics: the ratio between the signal intensity of spinal cord voxels and surrounding cerebrospinal fluid was correlated with DSC results ( p < 0.001). As predicted, variability in the manually-drawn masks influenced spatial normalization, and GM:WM contrast in the registered data showed significant effects of rater and dataset (rater: F (8, 160) = 23.57, P < 2 × 10 -16 , η 2 = 0.24; dataset: F (20, 160) = 22.00, P < 2 × 10 -16 , η 2 = 0.56). Registration differences propagated into subject-level activation maps which showed rater-dependent agreement with the reference. Although group-level activation maps differed between raters, no systematic bias was identified. Increasing consistency in manual contouring of spinal cord fMRI data improved co-registration and inter-rater agreement in activation mapping, however our results suggest that improvements in image acquisition and post-processing are also critical to address., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer JC-A declared a past co-authorship with several of the authors ZS, TP, and KW to the handling Editor., (Copyright © 2022 Hoggarth, Wang, Hemmerling, Vigotsky, Smith, Parrish, Weber and Bright.)

One of the most common types of models that helps us to understand neuron behavior is based on the Hodgkin-Huxley ion channel formulation (HH model). A major challenge with inferring parameters in HH models is non-uniqueness: many different sets of ion channel parameter values produce similar outputs for the same input stimulus. Such phenomena result in an objective function that exhibits multiple modes (i.e., multiple local minima). This non-uniqueness of local optimality poses challenges for parameter estimation with many algorithmic optimization techniques. HH models additionally have severe non-linearities resulting in further challenges for inferring parameters in an algorithmic fashion. To address these challenges with a tractable method in high-dimensional parameter spaces, we propose using a particular Markov chain Monte Carlo (MCMC) algorithm, which has the advantage of inferring parameters in a Bayesian framework. The Bayesian approach is designed to be suitable for multimodal solutions to inverse problems. We introduce and demonstrate the method using a three-channel HH model. We then focus on the inference of nine parameters in an eight-channel HH model, which we analyze in detail. We explore how the MCMC algorithm can uncover complex relationships between inferred parameters using five injected current levels. The MCMC method provides as a result a nine-dimensional posterior distribution, which we analyze visually with solution maps or landscapes of the possible parameter sets. The visualized solution maps show new complex structures of the multimodal posteriors, and they allow for selection of locally and globally optimal value sets, and they visually expose parameter sensitivities and regions of higher model robustness. We envision these solution maps as enabling experimentalists to improve the design of future experiments, increase scientific productivity and improve on model structure and ideation when the MCMC algorithm is applied to experimental data., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Wang, Rudi, Velasco, Sinha, Idumah, Powers, Heckman and Chardon.)

Memory-guided movements, vital to daily activities, are especially impaired in Parkinson's disease (PD). However, studies examining the effects of how information is encoded in memory and the effects of common treatments of PD, such as medication and subthalamic nucleus deep brain stimulation (STN-DBS), on memory-guided movements are uncommon and their findings are equivocal. We designed two memory-guided sequential reaching tasks, peripheral-vision or proprioception encoded, to investigate the effects of encoding type (peripheral-vision vs. proprioception), medication (on- vs. off-), STN-DBS (on- vs. off-, while off-medication), and compared STN-DBS vs. medication on reaching amplitude, error, and velocity. We collected data from 16 (analyzed n = 7) participants with PD, pre- and post-STN-DBS surgery, and 17 (analyzed n = 14) healthy controls. We had four important findings. First, encoding type differentially affected reaching performance: peripheral-vision reaches were faster and more accurate. Also, encoding type differentially affected reaching deficits in PD compared to healthy controls: peripheral-vision reaches manifested larger deficits in amplitude. Second, the effect of medication depended on encoding type: medication had no effect on amplitude, but reduced error for both encoding types, and increased velocity only during peripheral-vision encoding. Third, the effect of STN-DBS depended on encoding type: STN-DBS increased amplitude for both encoding types, increased error during proprioception encoding, and increased velocity for both encoding types. Fourth, STN-DBS was superior to medication with respect to increasing amplitude and velocity, whereas medication was superior to STN-DBS with respect to reducing error. We discuss our findings in the context of the previous literature and consider mechanisms for the differential effects of medication and STN-DBS., Competing Interests: Authors FD and MM received grant support from NIH. Author JR consults for Boston Scientific. Author SS received grant support from NIH, Medtronic, Abbott, and Boston Scientific. Author GP received grant support from NIH and the Parkinson's Disease Foundation. Author LV-M receives honoraria for consulting services/advisory boards from AbbVie, Abbott, Avion, and research support from AbbVie, Abbott, Biogen, Boston Sci., Chase, Medtronic, Neuroderm, Addex, UCB, and NIH. Author DC received grant support from NIH and Michael J. Fox and receives lecture and reviewer fees from NIH. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 David, Rivera, Entezar, Arora, Drane, Munoz, Rosenow, Sani, Pal, Verhagen-Metman and Corcos.)

Neuroimmune responses remain understudied in people with neck pain. This study aimed to (1) compare a broad range of systemic neuroimmune responses in people with non-specific neck pain ( N = 112), cervical radiculopathy ( N = 25), and healthy participants ( N = 23); and (2) explore their associations with clinical, psychological and lifestyle factors. Quantification of systemic neuroimmune responses involved ex vivo serum and in vitro evoked-release levels of inflammatory markers, and characterization of white blood cell phenotypes. Inflammatory indices were calculated to obtain a measure of total immune status and were considered the main outcomes. Differences between groups were tested using analyses of covariance (ANCOVA) and multivariable regression models. Compared to healthy participants, the ex vivo pro-inflammatory index was increased in people with non-specific neck pain (β = 0.70, p = 0.004) and people with cervical radiculopathy (β = 0.64, p = 0.04). There was no difference between non-specific neck pain and cervical radiculopathy (β = 0.23, p = 0.36). Compared to non-specific neck pain, people with cervical radiculopathy showed lower numbers of monocytes (β = -59, p = 0.01). There were no differences between groups following in vitro whole blood stimulation ( p ≥ 0.23) or other differences in the number and phenotype of white blood cells ( p ≥ 0.07). The elevated ex vivo neuroimmune responses in people with non-specific neck pain and radiculopathy support the contention that these conditions encompass inflammatory components that can be measured systemically. There were multiple significant associations with clinical, psychological and lifestyle factors, such as pain intensity (β = 0.25) and anxiety (β = 0.23) in non-specific neck pain, visceral adipose tissue (β = 0.43) and magnification (β = 0.59) in cervical radiculopathy, and smoking (β = 0.59) and visceral adipose tissue (β = 0.52) in healthy participants. These associations were modified by sex, indicating different neuroimmune associations for females and males., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Lutke Schipholt, Scholten-Peeters, Koop, Bonnet, Bontkes and Coppieters.)

Individuals with moderate-to-severe post-stroke hemiparesis cannot control proximal and distal joints of the arm independently because they are constrained to stereotypical movement patterns called flexion and extension synergies. Accumulating evidence indicates that these synergies emerge because of upregulation of diffusely projecting brainstem motor pathways following stroke-induced damage to corticofugal pathways. During our recent work on differences in synergy expression among proximal and distal joints, we serendipitously observed some notable characteristics of synergy-driven muscle activation. It seemed that: paretic wrist/finger muscles were activated maximally during contractions of muscles at a different joint; differences in the magnitude of synergy expression occurred when elicited via contraction of proximal vs. distal muscles; and associated reactions in the paretic limb occurred during maximal efforts with the non-paretic limb, the strength of which seemed to vary depending on which muscles in the non-paretic limb were contracting. Here we formally investigated these observations and interpreted them within the context of the neural mechanisms thought to underlie stereotypical movement patterns. If upregulation of brainstem motor pathways occurs following stroke-induced corticofugal tract damage, then we would expect a pattern of muscle dependency in the observed behaviors consistent with such neural reorganization. Twelve participants with moderate-to-severe hemiparetic stroke and six without stroke performed maximal isometric torque generation in eight directions: shoulder abduction/adduction and elbow, wrist, and finger flexion/extension. Isometric joint torques and surface EMG were recorded from shoulder, elbow, wrist, and finger joints and muscles. For some participants, joint torque and muscle activation generated during maximal voluntary contractions were lower than during maximal synergy-induced contractions (i.e., contractions about a different joint), particularly for wrist and fingers. Synergy-driven contractions were strongest when elicited via proximal joints and weakest when elicited via distal joints. Associated reactions in the wrist/finger flexors were stronger than those of other paretic muscles and were the only ones whose response depended on whether the non-paretic contraction was at a proximal or distal joint. Results provide indirect evidence linking the influence of brainstem motor pathways to abnormal motor behaviors post-stroke, and they demonstrate the need to examine whole-limb behavior when studying or seeking to rehabilitate the paretic upper limb., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 McPherson and Dewald.)

Translational research in behavioral neuroscience seeks causes and remedies for human mental health problems in animals, following leads imposed by clinical research in psychiatry. This endeavor faces several problems because scientists must read and interpret animal movements to represent human perceptions, mood, and memory processes. Yet, it is still not known how mammalian brains bundle all these processes into a highly compressed motor output in the brain stem and spinal cord, but without that knowledge, translational research remains aimless. Based on some four decades of experience in the field, the article identifies sources of interpretation problems and illustrates typical translational pitfalls. (1) The sensory world of mice is different. Smell, hearing, and tactile whisker sensations dominate in rodents, while visual input is comparatively small. In humans, the relations are reversed. (2) Mouse and human brains are equated inappropriately: the association cortex makes up a large portion of the human neocortex, while it is relatively small in rodents. The predominant associative cortex in rodents is the hippocampus itself, orchestrating chiefly inputs from secondary sensorimotor areas and generating species-typical motor patterns that are not easily reconciled with putative human hippocampal functions. (3) Translational interpretation of studies of memory or emotionality often neglects the ecology of mice, an extremely small species surviving by freezing or flight reactions that do not need much cognitive processing. (4) Further misinterpretations arise from confounding neuronal properties with system properties, and from rigid mechanistic thinking unaware that many experimentally induced changes in the brain do partially reflect unpredictable compensatory plasticity. (5) Based on observing hippocampal lesion effects in mice indoors and outdoors, the article offers a simplistic general model of hippocampal functions in relation to hypothalamic input and output, placing hypothalamus and the supraspinal motor system at the top of a cerebral hierarchy. (6) Many translational problems could be avoided by inclusion of simple species-typical behaviors as end-points comparable to human cognitive or executive processing, and to rely more on artificial intelligence for recognizing patterns not classifiable by traditional psychological concepts., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Lipp and Wolfer.)