Arm Choice Research Articles

Reaching the cognitive-motor interface: effects of cognitive load on arm choice and motor performance after stroke.

A vexing characteristic of motor disability after stroke is that many individuals fail to use their affected arm effectively despite having the capacity to do so, a phenomenon termed arm nonuse. Based on the hypothesis that nonuse is influenced by the competing cognitive demands of many daily activities, we examined the effects of cognitive load on arm choice and motor performance in individuals with stroke using a novel virtual reality paradigm that mimics the demands of real-life visual search, object selection, and reaching to targets. Twenty individuals with single left or right hemispheric chronic stroke (11 left cerebrovascular accident; 9 right cerebrovascular accident) and 10 age-matched neurotypical participants completed the Virtual Reality Arm Choice task, in which they reached for target objects in an array under varied cognitive demand. To manipulate cognitive demand, we varied the semantic similarity of objects in the reaching space and the presence or absence of a secondary task. The results showed reduced use of the paretic arm under increased demand. Under cognitive load, participants with stroke also showed slower reach initiation, slower movements, increased reach curvature, and increased performance differences between the paretic and non-paretic arms. The arm choice of neurotypical individuals was also modulated under cognitive load. These data indicate that cognitive factors influence arm choice and motor performance in naturalistic reaching tasks in individuals with chronic stroke. Performance decrements under cognitive load may in turn influence reduced paretic arm use during daily activities.

GOG-3097/ENGOT-ov81/GTG-UK/RAMP 301: a phase 3, randomized trial evaluating avutometinib plus defactinib compared with investigator’s choice of treatment in patients with recurrent low grade serous ovarian cancer

BackgroundThere are no approved treatments specifically for low grade serous ovarian cancer; current standard of care treatment options are limited in efficacy and tolerability. The combination of avutometinib with defactinib...

Guatemalan beaded lizards (Helodermatidae: Heloderma charlesbogerti) navigate and follow a scent trail in maze tasks.

Maze studies have provided substantial information about nonhuman cognition, such as insights on navigational strategies, spatial memory, and choice discriminations. This knowledge can aid in how we understand the foraging strategies of many animals, particularly understudied and endangered species, such as the Guatemalan beaded lizard (Heloderma charlesbogerti). These actively foraging lizards rely on chemoreception to locate prey, but it is unknown to what extent they engage in olfaction and vomerolfaction to hunt and navigate their environment. We investigated how Guatemalan beaded lizards moved through a physical maze. When navigating an eight-arm radial maze with all arms baited, lizards tended to turn into the immediately adjacent arm in a single direction, similar to other reptiles that have been tested in radial arm mazes. In a T-maze, the lizards had to discriminate between arms that contained scent and no-scent from a distance. They were generally unable to choose the baited (correct) arm at levels greater than chance, indicating an inability for this discrimination. With the addition of a scent trail, however, all lizards chose the baited arm at levels significantly above chance, and this increased accuracy was correlated with increased latency to make the arm choice. The lizards also demonstrated a decreased rate of tongue flicking as proximity to reward increased. Guatemalan beaded lizards can efficiently navigate a radial arm maze and can successfully use vomerolfaction with substrate-borne cues to locate prey, but they appear to have minimal olfaction abilities when sensing from a distance. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Female mice lacking membrane estrogen receptor alpha display impairments in spatial memory

Estrogens exert effects on cognition by acting on estrogen receptors (ER) including ERα. Activation of nuclear ERα results in classical genomic signaling leading to transcriptional changes that occur over hours to days. In contrast, activation of ERα localized to the membrane results in rapid signaling with effects occurring in seconds to minutes. The goal of the current study was to determine the role of membrane ERα in spatial memory. Female wildtype (WT) and transgenic mice that lack membrane ERα and express nuclear only ERα (NOER) were trained on an eight-arm radial-maze task. Following training, mice were tested on delay trials, in which delays ranging from 30 min to 5 h were inserted between the 4th and 5th arm choices. Performance was measured by number of proactive and retroactive errors. Proactive errors are short-term working memory errors defined by reentries into arms previously visited during the post-delay period or errors made during the pre-delay period. Retroactive errors are delay-dependent memory errors, defined as reentries into arms during the post-delay that were previously visited during the pre-delay. Consistent with a role for membrane ERα in rapid signaling, NOER mice made more proactive errors than WTs across all delays. NOER mice made more retroactive errors than WTs only after the 5-h delay. WT and NOER mice performed similarly on elevated plus maze and open field tests indicating no effects of membrane ERα on anxiety-related behavior or locomotor activity. Results reveal that membrane ERα plays important roles in both short-term and longer-term delay-dependent memory either directly or potentially indirectly through a role in the regulation of estradiol levels via the hypothalamic-pituitary-gonadal axis.

Investigator choice of standard therapy versus sequential novel therapy arms in the treatment of relapsed follicular lymphoma (REFRACT): study protocol for a multi-centre, open-label, randomised, phase II platform trial

BackgroundRelapsed or refractory follicular lymphoma (rrFL) is an incurable disease associated with shorter remissions and survival after each line of standard therapy. Many promising novel, chemotherapy-free therapies are in development, but few are licensed as their role in current treatment pathways is poorly defined.MethodsThe REFRACT trial is an investigator-initiated, UK National Cancer Research Institute, open-label, multi-centre, randomised phase II platform trial aimed at accelerating clinical development of novel therapies by addressing evidence gaps. The first of the three sequential novel therapy arms is epcoritamab plus lenalidomide, to be compared with investigator choice standard therapy (ICT). Patients aged 18 years or older with biopsy proven relapsed or refractory CD20 positive, grade 1-3a follicular lymphoma and assessable disease by PET-CT are eligible. The primary outcome is complete metabolic response by PET-CT at 24 weeks using the Deauville 5-point scale and Lugano 2014 criteria. Secondary outcomes include overall metabolic response, progression-free survival, overall survival, duration of response, and quality of life assessed by EQ-5D-5 L and FACT-Lym. The trial employs an innovative Bayesian design with a target sample size of 284 patients: 95 in the ICT arm and 189 in the novel therapy arms.DiscussionWhilst there are many promising novel drugs in early clinical development for rrFL, understanding the relative efficacy and safety of these agents, and their place in modern treatment pathways, is limited by a lack of randomised trials and dearth of published outcomes for standard regimens to act as historic controls. Therefore, the aim of REFRACT is to provide an efficient platform to evaluate novel agents against standard therapies for rrFL. The adaptive Bayesian power prior methodology design will minimise patient numbers and accelerate trial delivery.Trial registrationClinicalTrials.gov: NCT05848765; 08-May-2023.EudraCT2022-000677-75; 10-Feb-2022.

A phase II trial of cemiplimab alone or in combination with standard of care chemotherapy in locally advanced or metastatic penile carcinoma (EPIC trial).

TPS14 Background: Penile cancer is rare, <1% of male malignancies diagnosed each year, but its incidence is increasing with an 18% increase over the last decade projected to rise a further 9% in the next 10 years. Patients with locally advanced/metastatic penile cancer (la/mPC) have very few treatment options and there is a lack of clinical trial data to guide management. Cisplatin containing combination chemotherapy regimens are regarded as the standard of care (SOC) in this setting. However, with response rates of 50% or less there is a need to further improve treatment outcomes. PDL1 is upregulated in 40–60% of PC cases and is correlated with poor prognosis making a case for immunotherapy as a treatment for la/mPC. The PD-1 inhibitor cemiplimab is approved for patients with locally advanced or metastatic cutaneous squamous cell carcinoma (SCC) suggesting efficacy against penile SCC. The EPIC trial was set up to evaluate the benefit and safety of cemiplimab alone, or, in combination with SOC chemotherapy in patients with la/mPC. Methods: This is a non-randomised, 2 arm, phase II multi-centre trial. Arm 1 cemiplimab + SOC chemotherapy (local site choice of cisplatin/5FU, TPF or TIP regimes); Arm 2 single agent cemiplimab. The choice of arm decided by the investigator site based on chemotherapy eligibility. 47 patients will be recruited from 10 UK centres: 29 patients into ARM 1 who will receive 4 cycles of cemiplimab 350mg IV q3 weekly + SOC chemotherapy, followed by single agent cemiplimab x 30 cycles (24 months total). 18 patients into ARM 2 who will receive single agent cemiplimab 350mg IV q3 weekly x 34 cycles (24 months total). The primary endpoint is clinical benefit rate (CBR) of cemiplimab: objective response rate (ORR) plus stable disease as assessed radiologically (RECIST 1.1) at 12 weeks from first dose in patients with la/mPC. Secondary end-points include safety, tolerability, CBR at 1, 2 and 3 years, ORR, progression-free survival, overall survival and assessment of patient health status and quality of life using the patient reported outcome measures EQ-5D-5L and EORTC QLQ-C30. Each arm will be analysed separately as a Fleming A’Hern study α=0.05 + power (1-β)=0.8. Arm 1 assumes 25% meeting the clinical end point is a poor treatment (p0=0.25) and 50% is a good treatment (p1=0.5). Arm 2 assumes 5% meeting the clinical end point is a poor treatment (p0=0.05) and 25% is a good treatment (p1=0.25). Progress: By February 2023 10 UK sites had been opened to recruitment. The first patient entered the trial in November 2021 and to date 25 patients have been recruited into Arm 1 and 10 into Arm 2. Opening sites was slower than anticipated following emergence from the COVID pandemic. However, a recruitment rate of 1-2 patients per month has shown the feasibility of running a trial for this rare patient population. Clinical trial information: ISRCTN95561634 .

A metric for characterizing the arm nonuse workspace in poststroke individuals using a robot arm.

An overreliance on the less-affected limb for functional tasks at the expense of the paretic limb and in spite of recovered capacity is an often-observed phenomenon in survivors of hemispheric stroke. The difference between capacity for use and actual spontaneous use is referred to as arm nonuse. Obtaining an ecologically valid evaluation of arm nonuse is challenging because it requires the observation of spontaneous arm choice for different tasks, which can easily be influenced by instructions, presumed expectations, and awareness that one is being tested. To better quantify arm nonuse, we developed the bimanual arm reaching test with a robot (BARTR) for quantitatively assessing arm nonuse in chronic stroke survivors. The BARTR is an instrument that uses a robot arm as a means of remote and unbiased data collection of nuanced spatial data for clinical evaluations of arm nonuse. This approach shows promise for determining the efficacy of interventions designed to reduce paretic arm nonuse and enhance functional recovery after stroke. We show that the BARTR satisfies the criteria of an appropriate metric for neurorehabilitative contexts: It is valid, reliable, and simple to use.

Prey-dependent feeding behavior in a kelp-forest mesopredator, the California two-spot octopus

Predators have evolved a diverse behavioral repertoire to capture and handle prey. Within coleoid cephalopods, octopuses have developed dynamic movements associated with limb hyper-redundancy. As important mesopredators in coastal marine food webs, many species of octopuses are predominantly generalists, feeding on a wide variety of invertebrate and vertebrate prey. Despite their broad diets, few studies have examined the behavioral repertoire of octopus with respect to prey type. We compare how prey type may affect octopus feeding behavior by conducting controlled feeding trials during which we recorded California two-spot octopuses (Octopus bimaculoides, Pickford & McConnaughey, 1949) predating on a sessile prey (Protothaca staminea) and an active prey (Pachygraspus crassipes). We found that prey type had no effect on octopus body orientation, arm choice, nor eye use, but did have a significant influence on the timing events within a feeding sequence, the type of attack used, and attack kinematics. When feeding on clams, octopuses exhibited a shorter latency to move towards prey and make first contact with prey, longer attack decision and prey handling times, and slower attack speed and acceleration compared to when feeding on crabs. Octopuses tended to orient their right eye towards the prey for both first touch and attack during clam trials but during crab trials there was no eye bias. In all trials, eye use appeared to influence arm choice within each prey type. Finally, we report a previously undescribed behavior in the California two-spot octopus: a sinusoidal locomotory pattern that precedes the attack and was observed more commonly for crabs.

Active surveillance versus treatment in low-risk DCIS: Women’s preferences in the LORD-trial

BackgroundDuctal carcinoma in situ (DCIS) can progress to invasive breast cancer (IBC), but most DCIS lesions remain indolent. However, guidelines recommend surgery, often supplemented by radiotherapy. This implies overtreatment of indolent DCIS. The non-randomised patient preference LORD-trial tests whether active surveillance (AS) for low-risk DCIS is safe, by giving women with low-risk DCIS a choice between AS and conventional treatment (CT). Here, we aim to describe how participants are distributed among both trial arms, identify their motives for their preference, and assess factors associated with their choice. MethodsData were extracted from baseline questionnaires. Descriptive statistics were used to assess the distribution and characteristics of participants; thematic analyses to extract self-reported reasons for the choice of trial arm, and multivariable logistic regression analyses to investigate associations between patient characteristics and chosen trial arm. ResultsOf 377 women included, 76% chose AS and 24% CT. Most frequently cited reasons for AS were “treatment is not (yet) necessary” (59%) and trust in the AS-plan (39%). Reasons for CT were cancer worry (51%) and perceived certainty (29%). Women opting for AS more often had lower educational levels (OR 0.45; 95% confidence interval [CI], 0.22–0.93) and more often reported experiencing shared decision making (OR 2.71; 95% CI, 1.37–5.37) than women choosing CT. ConclusionThe LORD-trial is the first to offer women with low-risk DCIS a choice between CT and AS. Most women opted for AS and reported high levels of trust in the safety of AS. Their preferences highlight the necessity to establish the safety of AS for low-risk DCIS.

Specifics of Experimental Modeling 8-OH-DPAT-Induced Perseverative Behavior in Mice.

The effect of 5-HT1A receptor agonist 8-OH-DPAT (intraperitoneal injection in doses of 1, 2, and 4 mg/kg) on spontaneous alternation behavior of mice in Y-maze was studied without and with habituation procedure and food reward. In the first case, 8-OH-DPAT administration led to a decrease in spontaneous alternation and locomotor activity in mice. At the same time, 8-OH-DPAT treatment after habituation and food deprivation increased repeated choices of goal arms without affecting locomotor activity, which was consistent with perseverative behavior. 8-OH-DPAT-induced decrease in spontaneous alternation behavior in Y-maze in mice with habituation and food reward is the most suitable procedure for experimental modeling of the perseverative behavior and studying the anticompulsive activity of new substances.

Choice of Arm Use in Stroke Survivors is Largely Driven by the Energetic Cost of the Movement

Background The decision of which arm to use to achieve a goal depends on energetic costs and performance abilities of each arm. Following a stroke, there is a reduction in the use of the more-impaired arm. Is it because the energetic costs of the more-impaired arm are increased, or because its use dictates a lower chance of success? Objective We sought to elucidate the impact of energetic cost and task success on the arm choice of stroke survivors. Methods Thirteen chronic stroke survivors and thirteen neurologically-intact subjects participated in an experiment where they reached towards visual targets in a virtual-reality environment. Energetic cost of reaching with their less-used arm (nondominant/more-impaired) was adjusted by amplifying the range of motion, while task accuracy requirement was independently modulated by changing target size. Results Reducing the energic cost of reaching increased the use of the less-used arms in both groups, but by a greater amount in the stroke survivors. In contrast, lowering task accuracy requirement altered arm choice similarly in the two groups. The time spent in decision-making (reaction time) reflected different impacts of energetic cost and task success on the arm choice of the two groups. Conversely, velocity changes were similar between the groups. Conclusions The impact of energetic cost on arm choice of stroke survivors is greater than neurologically-intact subjects. Thus, the reduction in the use of the impaired arm following stroke may be primarily due to a subjective increase in the effort it takes to use that arm.

Effects of rearing with vertical structures on the ontogeny of depth perception in laying hens

Multi-tiered aviary systems provide laying hens with opportunities for species-specific behaviors, including vertical and horizontal movement. However, collisions and failed landings that occur during vertical movement can be associated with injuries. Previous studies suggest that floor rearing of pullets with minimal access to elevated structures may negatively impact adult laying hens’ ability to navigate vertical space. However, it is not clear whether this is due to deficits in physical ability or differences in depth perception. This was investigated in pullets and egg-laying hens using a modified Y-maze task and a visual cliff task at 7–8, 15–16, and 29–30 weeks of age. Dekalb White pullets (N = 450) were reared in three different environments until 16 weeks of age: floor, single-tier aviary, and two-tier aviary. From 16 weeks of age, all birds were housed in a multi-tier aviary. The Y-maze task consisted of two arms that were either a ratio of 1:3 or 1:1 in length. Each bird’s ability to discriminate the different arm lengths was evaluated based on latency to exit and arm choice. The illusion of depth over a plexiglass floor was tested in the visual cliff task at 15, 30, and 90 cm. Birds were given 1.5 min to either leave the start perch by jumping to a platform suspended over the visual cliff, or step down off the perch to the shallow side. Latency to jump to the platform and frequency of looking down over the visual cliff were recorded. There were no main effects of age or rearing treatment on behavior in the Y-maze, with all birds choosing the shorter arm more than chance (p < 0.001). Regardless of cliff height, birds reared on the floor were less likely to cross the visual cliff at 8 and 16 weeks of age than single and two-tier treatment birds (p = 0.01). However, these differences were not observed after they were given experience with elevated structures in the adult aviary. The results of the present study suggest that the lack of exposure to vertical complexity during rearing do not cause long-term detriments to depth perception, but could impact successful engagement with elevated heights (i.e., hesitancy to access vertical structures). Further research is needed to determine the timing, quality, and quantity of elevated height exposure that is needed in the rearing environment to encourage sufficient use of vertical space in the adult aviary for cage-free laying hens.

The Price of Incentivizing Exploration: A Characterization via Thompson Sampling and Sample Complexity

We consider “incentivized exploration”: a version of multiarmed bandits where the choice of arms is controlled by self-interested agents. The algorithm can only issue recommendations and needs to incentivize the agents to explore, even though they prefer to exploit. The algorithm controls the flow of information and relies on information asymmetry to create incentives. This line of work, motivated by misaligned incentives in recommendation systems, has received considerable attention in the “economics and computation” community. We focus on the “price of incentives”: the loss in performance, broadly construed, incurred for the sake of incentive compatibility. We prove that Thompson sampling, a standard bandit algorithm, is incentive compatible if initialized with sufficiently many data points. The performance loss because of incentives is, therefore, limited to the initial rounds when these data points are collected. The problem is largely reduced to that of sample complexity. How many rounds are needed to collect even one sample of each arm? We zoom in on this question, which is perhaps the most basic question one could ask about incentivized exploration. We characterize the dependence on agents' beliefs and the number of arms (which was essentially ignored in prior work), providing matching upper and lower bounds. Typically, the optimal sample complexity is polynomial in the number of arms and exponential in the “strength of beliefs.”

Quality of Control Arms in Randomized Trials of Chronic Lymphocytic Leukemia Enrolling in the USA: A Systematic Review

Introduction: Many ongoing clinical trials in chronic lymphocytic leukemia (CLL) are investigating "chemotherapy-free” combinations of novel agents administered in a time-limited manner both in the frontline and relapsed/refractory setting. However, there is a concern that the results of trials testing these novel treatment combinations can be difficult to interpret if the therapy in the control groups is suboptimal and/or are not commonly used in the USA. A suboptimal control group reduces the trial's external validity as it introduces a bias in favor of the experimental arm. To date, an empirical evaluation of the quality of control groups in randomized trials of chronic lymphocytic leukemia has not been undertaken. We sought to carry out a systematic review of randomized trials of CLL between Jan 2010 and Dec 2021 to establish the quality of the control group therapies compared to USA standards as determined by NCCN and expert reviews. Methods: PubMed (MEDLINE), Embase, Cochrane, Scopus, and Web of Science were searched for articles of randomized trials of CLL that enrolled participants in the USA between January 1, 2010, to December 31, 2021. Standard-of-care therapy for the USA was determined by evaluating the literature (expert reviews) and published guidelines (mainly NCCN) prior to the start of trial enrollment. The percentage of randomized trials that used suboptimal control arms was then calculated. A control group therapy was considered suboptimal if the choice of control arm was restricted (i.e., excluded an active therapy), and/or if prior randomized trials had shown the control agent (or class) was inferior to an available alternative or by limiting combinations in the control group. Results: A total of 1775 articles with our initial search strategy. 625 records were duplicates and were excluded. We screened 1150 articles in our primary screening. Of these, 156 were excluded due to being non-CLL studies, 117 records were excluded due to being duplicates, abstracts, trials in progress, and subgroup analysis, 258 records were excluded due to being review articles, and case series/reports, 564 records were excluded due to being single-arm studies. 55 articles were eligible for secondary screening. Of these, 29 did not meet inclusion criteria due to not enrolling in the U.S and 7 were excluded due to enrollment start date before Jan 2010. 19 trails were eligible for the final analysis. Of the 19 trials that were assessed in the final analysis, we identified 10 (52%) trials that enrolled patients in a suboptimal control arm. When classified further by the nature of the suboptimal control arm, 7 (36%) trials omitted active treatment in the control arm by using a control agent known to be inferior to other available agents or not allowing combinations, and 3 (16%) trials omitted active treatment in control arm by limiting investigator's choice. Conclusion: Our findings show that half of randomized trials of CLL use a suboptimal control group. Although limiting investigator choice is common within the context of a randomized trial and may not be detrimental, approx. a third of randomized trials use control agents that are known to be inferior to other available agents. The choice of control arm of trials enrolling in the USA should be optimized to ensure that it matches what most clinicians would prescribe outside a clinical trial setting. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Information-gathering in latent bandits

In the latent bandit problem, the learner has access to reward distributions and – for the non-stationary variant – transition models of the environment. The reward distributions are conditioned on the arm and unknown latent states. The goal is to use the reward history to identify the latent state, allowing for the optimal choice of arms in the future. The latent bandit setting lends itself to many practical applications, such as recommender and decision support systems, where rich data allows the offline estimation of environment models with online learning remaining a critical component. Previous solutions in this setting always choose the highest reward arm according to the agent’s beliefs about the state, not explicitly considering the value of information-gathering arms. Such information-gathering arms do not necessarily provide the highest reward, thus may never be chosen by an agent that chooses the highest reward arms at all times.In this paper, we present a method for information-gathering in latent bandits. Given particular reward structures and transition matrices, we show that choosing the best arm given the agent’s beliefs about the states incurs higher regret. Furthermore, we show that by choosing arms carefully, we obtain an improved estimation of the state distribution, and thus lower the cumulative regret through better arm choices in the future. Through theoretical analysis we show that the proposed method retains the sub-linear regret rate of previous methods while having much better problem dependent constants. We evaluate our method on both synthetic and real-world data sets, showing significant improvement in regret over state-of-the-art methods.

A phase II trial of cemiplimab alone or in combination with standard of care chemotherapy in locally advanced or metastatic penile carcinoma (EPIC Trial).

TPS5094 Background: Penile cancer (PC) is rare but its incidence is increasing, with an increase of 21% over the last decade. The rarity of this cancer means a paucity of large prospective clinical trial data to guide the management of locally advanced/metastatic penile cancer (la/mPC). Cisplatin containing combination chemotherapy regimens are widely regarded as the standard of care (SOC) in this setting. However, with response rates of about 50% there is a need to further improve treatment outcomes. PDL1 is upregulated in 40–60% of PC cases and is correlated with poor prognosis making a case for immunotherapy as a treatment for la/mPC. Currently there are ongoing clinical trials exploring immunotherapy on penile carcinoma, however, none of these trials are looking at the combination of immunotherapy and chemotherapy. The novel immune checkpoint inhibitor cemiplimab has been approved for locally advanced and metastatic cutaneous squamous cell carcinoma (mcSCC). In view of this, we sought to evaluate the benefit and safety of cemiplimab alone, or, in combination with SOC chemotherapy in patients with la/mPC. Methods: This is a non-randomised, open label, two arm phase II multi-centre trial of single agent cemiplimab versus cemiplimab + SOC chemotherapy in la/mPC, choice of arm decided by the investigator site based on chemotherapy eligibility. Eligibility includes patients with la/mPC who are candidates for immunotherapy +/- SOC chemotherapy (local UK centre choice of cisplatin/5FU or TPF or TIP regimes). 47 patients will be recruited from 10 UK centres: 29 patients into ARM 1 who will receive 4 cycles of cemiplimab 350mg IV q3 weekly + SOC chemotherapy, followed by single agent cemiplimab x 30 cycles (24 months total). 18 patients into ARM 2 who will receive single agent cemiplimab 350mg IV q3 weekly, up to 34 cycles (24 months total). The primary endpoint is clinical benefit rate (CBR) of cemiplimab: objective response rate (ORR) plus stable disease as assessed radiologically (RECIST 1.1) post cycle 4 in patients with la/mPC. Secondary end-points include safety, tolerability, CBR at 1, 2 and 3 years, ORR, progression-free survival, overall survival and assessment of patient health status and quality of life using the patient reported outcome measures EQ-5D-5L and EORTC QLQ-C30. Each arm will be analysed separately as a Fleming A’Hern study α = 0.05 + power (1-β) = 0.8. Arm 1 assumes 25% meeting the clinical end point is a poor treatment (p0 = 0.25) and 50% is a good treatment (p1 = 0.5). Arm 2 assumes 5% meeting the clinical end point is a poor treatment (p0 = 0.05) and 25% is a good treatment (p1 = 0.25). To date, 4 patients have been recruited from 2 centres with the aim to open all UK centres to recruitment by June 2022. The EPIC trial is NCRN badged. Clinical trial information: 95561634.

Express arm responses appear bilaterally on upper-limb muscles in an arm choice reaching task

When required, humans can generate very short latency reaches toward visual targets, such as catching a falling cellphone. During such rapid reaches, express arm responses are the first wave of upper limb muscle recruitment, occurring ∼80-100 ms after target appearance. There is accumulating evidence that express arm responses arise from signaling along the tecto-reticulo-spinal tract, but the involvement of the reticulospinal tract has not been well studied. Since the reticulospinal tract projects bilaterally, we studied whether express arm responses would be generated bilaterally. Human participants (n = 14; 7 females) performed visually guided reaches in a modified emerging target paradigm where either arm could intercept the target. We recorded electromyographic activity bilaterally from the pectoralis major muscle. Our analysis focused on target locations where participants reached with the right arm on some trials, and the left arm on others. In support of the involvement of the reticulospinal tract, express arm responses persisted bilaterally regardless of which arm reached to the target. The latency and magnitude of the express arm response did not depend on whether the arm was chosen to reach or not. However, on the reaching arm, the magnitude of the express arm response was correlated to the level of anticipatory activity. The bilateral generation of express arm responses supports the involvement of the reticulospinal tract. We surmise that the correlation between anticipatory activity and the magnitude of express arm responses on the reaching arm arises from convergence of cortically derived signals with a parallel subcortical pathway mediating the express arm response.NEW & NOTEWORTHY Express arm responses have been proposed to arise from the tecto-reticulo-spinal tract originating within the superior colliculus, but the involvement of the reticulospinal tract has not been well studied. Here, we show these responses appear bilaterally in a task where either arm can reach to a newly appearing stimulus. Our results suggest that the most rapid visuomotor transformations for reaching are performed by a subcortical pathway.

Landmark‐guided T‐maze learning in the wolf spiderTigrosa helluo

AbstractSpatial learning and navigation may be acquired through idiothetic information (i.e., self‐referential movement cues) or allothetic cues (e.g., external landmarks). Animals may use specific types of landmarks to navigate known as reference frames. A reference frame is an environmental shape or boundary that provides a framework for spatial localization. Wolf spiders produce draglines of silk as they move through the environment that could serve as reference frames and may predispose spiders to use other reference frames to navigate. Using a modified water T‐maze, we recorded the ability of adult femaleTigrosa helluowolf spiders to correctly navigate toward a target goal. We measured variation in spatial learning of the target location with and without a reference frame landmark (tape marking the correct path). Females were trained over ten consecutive trials to successfully achieve the goal. Training trials were then repeated the following day for each subject for a total of 20 trials over two days. In the landmark condition, after the 20 trials, we reversed the reference frame to the incorrect arm choice to test for a decline in performance. For each trial, we measured the latency to achieve the goal and number of reversions or path retracing. Results indicate significantly shorter time to goal over subsequent trials with shorter mean latency to achieve the goal on the second day compared with the first. The landmark treatment showed significantly fewer wrong turns and path retracings than the control, and the reversal of the reference frame significantly increased the latency to achieve the goal. Wolf spiders can learn simple T‐maze navigation under our testing conditions, but learning is enhanced when reference frames are present. Landmarks are important for spider allothetic spatial navigation, and learned spatial navigation tasks are better retained over two days in the presence of reference frames.

Relevant factors for arm choice in reaching movement: a scoping review.

[Purpose] Arm choice is an unconscious action selection performed in daily life. Even if hemiparetic stroke patients can use their paretic arm, they compensate for their movements with their non-paretic arm, leading to decreased function of their paretic arm. Therefore, we need to encourage stroke patients to actively use their paretic arm. For this purpose, it is imperative to understand the process of selection of the left or right hand by patients. Here, we conducted a scoping review to summarize the findings of previous studies on factors and brain regions related to choice of arm. [Methods] We used PubMed/Medline, EBSCO, and the Cochrane Library to obtain research literature according to the PRISMA Extension for Scoping Reviews guidelines. [Results] Twenty-five of the 81 articles obtained from the search met the defined criteria. Cost, success, and dominance were investigated as relevant factors for arm choice. We also extracted articles examining the relationship between the posterior parietal and premotor cortex activity and arm choice. [Conclusion] From these results, we considered ways to facilitate the use of the paretic arm, such as the use of virtual reality systems or exoskeletal robots to modulate the reaching cost and success rates, or non-invasive brain stimulation methods to modulate brain activity.

Effort, success, and side of lesion determine arm choice in individuals with chronic stroke.

In neurotypical individuals, arm choice in reaching movements depends on expected biomechanical effort, expected success, and a handedness bias. Following a stroke, does arm choice change to account for the decreased motor performance, or does it follow a preinjury habitual preference pattern? Participants with mild-to-moderate chronic stroke who were right-handed before stroke performed reaching movements in both spontaneous and forced-choice blocks, under no-time, medium-time, and fast-time constraint conditions designed to modulate reaching success. Mixed-effects logistic regression models of arm choice revealed that expected effort predicted choices. However, expected success only strongly predicted choice in left-hemiparetic individuals. In addition, reaction times decreased in left-hemiparetic individuals between the no-time and the fast-time constraint conditions but showed no changes in right-hemiparetic individuals. Finally, arm choice in the no-time constraint condition correlated with a clinical measure of spontaneous arm use for right-, but not for left-hemiparetic individuals. Our results are consistent with the view that right-hemiparetic individuals show a habitual pattern of arm choice for reaching movements relatively independent of failures. In contrast, left-hemiparetic individuals appear to choose their paretic left arm more optimally: that is, if a movement with the paretic arm is predicted to be not successful in the upcoming movement, the nonparetic right arm is chosen instead.NEW & NOTEWORTHY Although we are seldom aware of it, we constantly make decisions to use one arm or the other in daily activities. Here, we studied whether these decisions change following stroke. Our results show that effort, success, and side of lesion determine arm choice in a reaching task: whereas left-paretic individuals modified their arm choice in response to failures in reaching the target, right-paretic individuals showed a pattern of choice independent of failures.