Liver function and portal-systemic shunting quantified by the oral cholate challenge test and risk for large oesophageal varices.

BACKGROUND: The quantitative HepQuant SHUNT test of liver function and physiology generates a disease severity index (DSI) that correlates with risk for clinical complications, such as large oesophageal varices (LEVs). A derivative test, HepQuant DuO, generates an equivalent DSI and simplifies testing by requiring only oral administration of the test solution and two blood samples at 20 and 60 min. AIMS: Since the DSIs measured from DuO and SHUNT are equivalent, we compared the diagnostic performance for large oesophageal varices (LEVs) between the DSIs measured from DuO and SHUNT tests. METHODS: This study combined the data from two prospectively conducted US studies: HALT-C and SHUNT-V. A total of 455 subjects underwent both the SHUNT test and esophagogastroduodenoscopy (EGD). RESULTS: DSI scores correlated with the probability of LEVs (p < 0.001) and demonstrated a stepwise increase from healthy lean controls without liver disease to subjects with chronic liver disease and no, small or large varices. Furthermore, a cutoff of DSI ≤ 18.3 from DuO had a sensitivity of 0.98 (missing only one case) and, if applied to the endoscopy (EGD) decision, would have prevented 188 EGDs (41.3%). The AUROC for DSI from DuO did not differ from that of the reference SHUNT test method (0.82 versus 0.81, p = 0.3500). CONCLUSIONS: DSI from HepQuant DuO links liver function and physiology to the risk of LEVs across a wide spectrum of patient characteristics, disease aetiologies and liver disease severity. DuO is minimally invasive, easy to administer, quantitative and may aid the decision to avoid or perform EGD for LEVs.

Visuospatial memory in apraxia: Exploring quantitative drawing metrics to assess the representation of local and global information.

Neuropsychological evidence suggests that visuospatial memory is subserved by two separable processing systems, with dorsal underpinnings for global form and ventral underpinnings for the integration of part elements. Previous drawing studies have explored the effects of Gestalt organisation upon memory for hierarchical stimuli, and we here present an exploratory study of an apraxic dorsal stream patient's (MH) performance. We presented MH with a stimulus set (previously reported by Riddoch et al., Cognitive Neuropsychology, 20(7), 641-671, 2003) and devised a novel quantitative scoring system to obtain a finer grain of insight into performance. Stimuli possessed either good or poor Gestalt qualities and were reproduced in a copy condition and two visual memory conditions (with unlimited viewing before the model was removed, or with 3 s viewing). MH's copying performance was impaired in comparison to younger adult and age-matched older adult controls, with a variety of errors at the local level but relatively few at the global level. However, his performance in the visual memory conditions revealed impairments at the global level. For all participants, drawing errors were modulated by the Gestalt qualities of the stimuli, with accuracy at the global and local levels being lesser for poor global stimuli in all conditions. These data extend previous observations of this patient, and support theories that posit interaction between dorsal and ventral streams in the representation of hierarchical stimuli. We discuss the implications of these findings for our understanding of visuospatial memory in neurological patients, and also evaluate the application of quantitative metrics to the interpretation of drawings.

Hydrocephalus: A neuropsychological and theoretical primer.

Hydrocephalus is a common neurological condition, the hallmark feature of which is an excess in production, or accumulation, of cerebrospinal fluid in the ventricles. Although it is associated with diffuse damage to paraventricular brain areas, patients are broadly typified by a particular pattern of cognitive impairments that include deficits in working memory, attention, and spatial abilities. There have, however, been relatively few neuropsychological accounts of the condition. Moreover, theories of the relationship between aetiology and impairment appear to have emerged in isolation of each other, and proffer fundamentally different accounts. In this primer, we aim to provide a comprehensive and contemporary overview of hydrocephalus for the neuropsychologist, covering cognitive sequelae and theoretical interpretations of their origins. We review clinical and neuropsychological assays of cognitive profiles, along with the few studies that have addressed more integrative behaviours. In particular, we explore the distinction between congenital or early-onset hydrocephalus with a normal-pressure variant that can be acquired later in life. The relationship between these two populations is a singularly interesting one in neuropsychology since it can allow for the examination of typical and atypical developmental trajectories, and their interaction with chronic and acute impairment, within the same broad neurological condition. We reflect on the ramifications of this for our subject and suggest avenues for future research.

The developmental trajectories of children's reorientation to global and local properties of environmental geometry.

The way in which organisms represent the shape of their environments during navigation has been debated in cognitive, comparative, and developmental psychology. While there is evidence that adult humans encode the entire boundary shape of an environment (a global-shape representation), there are also data demonstrating that organisms reorient using only segments of the boundary that signal a goal location (a local-shape representation). Developmental studies offer unique insights into this debate; however, most studies have used designs that cannot dissociate the type of boundary-shape representation that children use to guide reorientation. Thus, we examined the developmental trajectories of children's reorientation according to local and global boundary shape. Participants aged 6-12 years were trained to find a goal hidden in one corner of a virtual arena, after which they were required to reorient in a novel test arena. From 10.5 years, children performed above chance when the test arena permitted reorientation based only on local-shape (Experiment 2), or only global-shape (Experiment 3) information. Moreover, when these responses were placed into conflict, older children reoriented with respect to global-shape information (Experiment 4). These age-related findings were not due to older children being better able to reorient in virtual environments per se: when trained and tested within the same environment (Experiment 1), children performed above chance from 6 years. Together, our results suggest (a) the ability to reorient on the basis of global- and local-shape representations develops in parallel, and (b) shape-based information is weighted to determine which representation informs reorientation. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Redefinition of Fatty Liver Disease from NAFLD to MAFLD through the Lens of Drug Development and Regulatory Science.

Metabolic (dysfunction)-associated fatty liver disease (MAFLD) affects a third of the population and is a leading cause of liver-related death. Since no effective treatments exist, novel approaches to drug development are required. Unfortunately, outdated terminology and definitions of the disease are hampering efforts to develop new drugs and treatments. An international consensus panel has put forth an influential proposal for the disease to be renamed from nonalcoholic fatty liver disease (NAFLD) to MAFLD, including a proposal for how the disease should be diagnosed. As allies with the many stakeholders in MAFLD care-including patients, patients' advocates, clinicians, researchers, nurse and allied health groups, regional societies, and others-we are aware of the negative consequences of the NAFLD term and definition. We share the sense of urgency for change and will act in new ways to achieve our goals. Although there is much work to be done to overcome clinical inertia and reverse worrisome recent trends, the MAFLD initiative provides a firm foundation to build on. It provides a roadmap for moving forward toward more efficient care and affordable, sustainable drug and device innovation in MAFLD care. We hope it will bring promising new opportunities for a brighter future for MAFLD care and improve care and outcomes for patients of one of the globe's largest and costliest public health burdens. From this viewpoint, we have revisited this initiative through the perspectives of drug development and regulatory science.

Searching for individual determinants of probabilistic cueing in large-scale immersive virtual environments.

Large-scale search behaviour is an everyday occurrence, yet its underlying mechanisms are not commonly examined within experimental psychology. Key to efficient search behaviour is the sensitivity to environmental cues that might guide exploration, such as a target appearing with greater regularity in one region than another. Spatial cueing by probability has been examined in visual search paradigms, but the few studies that have addressed its contribution to large-scale search and foraging present contrasting accounts of the conditions under which a cueing effect can be reliably observed. In the present study, participants physically searched a virtual arena by inspecting identical locations until they found the target. The target was always present, although its location was probabilistically defined so that it appeared in the cued hemispace on 80% of trials. In Experiment 1, when participants' starting positions were stable, a probabilistic cueing effect was observed, with a strong bias towards searching the cued side. In Experiment 2, the starting position changed across the experiment, such that the cued region was defined in allocentric co-ordinates only. In this case, a probabilistic cueing effect was not observed across the sample. Analysis of individual differences in Experiment 2 suggests, however, that some participants may have learned the contingency underpinning the target's location, although these differences were unrelated to other tests of visuospatial ability. These results suggest that the ability to learn the likelihood of an item's fixed location when starting from different perspectives is driven by individual differences in other cognitive or perceptual factors.

Sources of variation in search and foraging: A theoretical perspective.

Search-the problem of exploring a space of alternatives to identify target goals-is a fundamental behaviour for many species. Although its foundation lies in foraging, most studies of human search behaviour have been directed towards understanding the attentional mechanisms that underlie the efficient visual exploration of two-dimensional (2D) scenes. With this review, we aim to characterise how search behaviour can be explained across a wide range of contexts, environments, spatial scales, and populations, both typical and atypical. We first consider the generality of search processes across psychological domains. We then review studies of interspecies differences in search. Finally, we explore in detail the individual and contextual variables that affect visual search and related behaviours in established experimental psychology paradigms. Despite the heterogeneity of the findings discussed, we identify that variations in control processes, along with the ability to regulate behaviour as a function of the structure of search space and the sampling processes adopted, to be central to explanations of variations in search behaviour. We propose a tentative theoretical model aimed at integrating these notions and close by exploring questions that remain unaddressed.

Room to breathe: Using adaptive architecture to examine the relationship between alexithymia and interoception.

OBJECTIVE: Individuals with alexithymia experience difficulties interpreting emotional states in self and others, which has been associated with interoceptive impairment. Current theories are primarily based on subjective and conscious measures of interoceptive sensitivity, such as heartrate detection, but it is unclear whether similar observations would be found for objective or implicit psychophysiological measures. The present exploratory study assesses the potential of a novel assay through the use of adaptive immersive architecture [ExoBuilding]. METHODS: N = 88 participants were screened for alexithymic traits and N = 27 individuals, representing the range of scores, were sampled to participate in the behavioural task. In a repeated-measures design, participants were placed within ExoBuilding and asked to match their respiration to its movement. Performance was compared to a two-dimensional pacer condition. Behavioural (accuracy) and psychophysiological (Respiratory Sinus Arrhythmia [RSA] and heartrate) measures were compared across conditions, and also related to individual alexithymic traits. RESULTS: Participants with higher levels of alexithymia performed less accurately than participants with lower levels, in both conditions. High-alexithymia participants showed a smaller reduction in heartrate over the course of the ExoBuilding condition than low-alexithymia participants, although there were no differences in RSA between conditions or participants. CONCLUSION: Alexithymia extends beyond conscious interoceptive activities and is also observed in immersive contexts that usually exert psychophysiological effects on typical occupants. These initial findings highlight the importance of considering both conscious and implicit measures of interoception, and we suggest ways in which theories of alexithymia might benefit from capturing this distinction.

Crossing boundaries: Global reorientation following transfer from the inside to the outside of an arena.

In 2 spatial navigation experiments, human participants were asked to find a hidden goal (a WiFi signal) that was located in 1 of the right-angled corners of a kite-shaped (Experiment 1) or a cross-shaped (Experiment 2) virtual environment. Goal location was defined solely with respect to the geometry of the environment. Following this training, in a test conducted in extinction, participants were placed onto the outside of the same environments and asked to locate the WiFi signal. The results of both experiments revealed that participants spent more time searching in regions on the outside of the environments that were closest to where the WiFi signal was located during training. These results are difficult to explain in terms of analyses of spatial navigation and reorientation that emphasize the role of local representational encoding or view matching. Instead, we suggest that these results are better understood in terms of a global representation of the shape of the environment. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Thinking outside of the box II: Disrupting the cognitive map.

A number of influential spatial learning theories posit that organisms encode a viewpoint independent (i.e. allocentric) representation of the global boundary shape of their environment in order to support spatial reorientation and place learning. In contrast to the trial and error learning mechanisms that support domain-general processes, a representation of the global-shape of the environment is thought to be encoded automatically as part of a cognitive map, and without interference from other spatial cues. To date, however, this core theoretical assumption has not been appropriately examined. This is because previous attempts to address this question have failed to employ tasks that fully dissociate reorientation based on an allocentric representation of global-shape from egocentric reorientation strategies. Here, we address this issue in two experiments. Participants were trained to navigate to a hidden goal on one side of a virtual arena (e.g. the inside) before being required to find the same point on the alternative side (e.g. the outside). At test, performing the correct search behaviour requires an allocentric representation of the global boundary-shape. Using established associative learning procedures of overshadowing and blocking, we find that search behaviour at test is disrupted when participants were able to form landmark-goal associations during training. These results demonstrate that encoding of an allocentric representation of boundary information is susceptible to interference from landmark cues, and is not acquired through special means. Instead, the results suggest that allocentric representations of environmental boundaries are acquired through the same kind of error-correction mechanisms that support domain-general non-spatial learning.

Body representation difficulties in children and adolescents with autism may be due to delayed development of visuo-tactile temporal binding.

Recent research suggests visuo-tactile binding is temporally extended in autism spectrum disorders (ASD), although it is not clear whether this specifically underlies altered body representation in this population. In the current study children and adolescents with ASD, and typically developing controls, placed their hand into mediated reality system (MIRAGE) and saw two identical live video images of their own right hand. One image was in the proprioceptively correct location (veridical hand) and the other was displaced to either side. While visuo-tactile feedback was applied via brushstroke to the participant's (unseen) right finger, they viewed one hand image receiving synchronous brushstrokes and the other receiving brushstrokes with a temporal delay (60, 180 and 300ms). After brushing, both images disappeared from view and participants pointed to a target, with direction of movement indicating which hand was embodied. ASD participants, like younger mental aged-matched controls, showed reduced embodiment of the spatially incongruent, but temporally congruent, hand compared to chronologically age-matched controls at shorter temporal delays. This suggests development of visuo-tactile integration may be delayed in ASD. Findings are discussed in relation to atypical body representation in ASD and how this may contribute to social and sensory difficulties within this population.

Transcranial Direct Current Stimulation (tDCS): A Beginner's Guide for Design and Implementation.

Transcranial direct current stimulation (tDCS) is a popular brain stimulation method that is used to modulate cortical excitability, producing facilitatory or inhibitory effects upon a variety of behaviors. There is, however, a current lack of consensus between studies, with many results suggesting that polarity-specific effects are difficult to obtain. This article explores some of these differences and highlights the experimental parameters that may underlie their occurrence. We provide a general, practical snapshot of tDCS methodology, including what it is used for, how to use it, and considerations for designing an effective and safe experiment. Our aim is to equip researchers who are new to tDCS with the essential knowledge so that they can make informed and well-rounded decisions when designing and running successful experiments. By summarizing the varied approaches, stimulation parameters, and outcomes, this article should help inform future tDCS research in a variety of fields.

Cultural differences in attention: Eye movement evidence from a comparative visual search task.

Individual differences in visual attention have been linked to thinking style: analytic thinking (common in individualistic cultures) is thought to promote attention to detail and focus on the most important part of a scene, whereas holistic thinking (common in collectivist cultures) promotes attention to the global structure of a scene and the relationship between its parts. However, this theory is primarily based on relatively simple judgement tasks. We compared groups from Great Britain (an individualist culture) and Saudi Arabia (a collectivist culture) on a more complex comparative visual search task, using simple natural scenes. A higher overall number of fixations for Saudi participants, along with longer search times, indicated less efficient search behaviour than British participants. Furthermore, intra-group comparisons of scan-path for Saudi participants revealed less similarity than within the British group. Together, these findings suggest that there is a positive relationship between an analytic cognitive style and controlled attention.

Drawing Firmer Conclusions: Autistic Children Show No Evidence of a Local Processing Bias in a Controlled Copying Task.

Drawing tasks are frequently used to test competing theories of visuospatial skills in autism. Yet, methodological differences between studies have led to inconsistent findings. To distinguish between accounts based on local bias or global deficit, we present a simple task that has previously revealed dissociable local/global impairments in neuropsychological patients. Autistic and typical children copied corner elements, arranged in a square configuration. Grouping cues were manipulated to test whether global properties affected the accuracy of reproduction. All children were similarly affected by these manipulations. There was no group difference in the reproduction of local elements, although global accuracy was negatively related to better local processing for autistic children. These data speak against influential theories of visuospatial differences in autism.

Thinking outside of the box: Transfer of shape-based reorientation across the boundary of an arena.

The way in which human and non-human animals represent the shape of their environments remains a contentious issue. According to local theories of shape learning, organisms encode the local geometric features of the environment that signal a goal location. In contrast, global theories of shape learning suggest that organisms encode the overall shape of the environment. There is, however, a surprising lack of evidence to support this latter claim, despite the fact that common behaviours seem to require encoding of the global-shape of an environment. We tested one such behaviour in 5 experiments, in which human participants were trained to navigate to a hidden goal on one side of a virtual arena (e.g. the inside) before being required to find the same point on the alternative side (e.g. the outside). Participants navigated to the appropriate goal location, both when inside and outside the virtual arena, but only when the shape of the arena remained the same between training and test (Experiments 1a and 1b). When the arena shape was transformed between these stages, participants were lost (Experiments 2a and 2b). When training and testing was conducted on the outside of two different-shaped arenas that shared local geometric cues participants once again explored the appropriate goal location (Experiment 3). These results provide core evidence that humans encode a global representation of the overall shape of the environments in, or around, which they navigate.

Blocking spatial navigation across environments that have a different shape.

According to the geometric module hypothesis, organisms encode a global representation of the space in which they navigate, and this representation is not prone to interference from other cues. A number of studies, however, have shown that both human and non-human animals can navigate on the basis of local geometric cues provided by the shape of an environment. According to the model of spatial learning proposed by Miller and Shettleworth (2007, 2008), geometric cues compete for associative strength in the same manner as non-geometric cues do. The experiments reported here were designed to test if humans learn about local geometric cues in a manner consistent with the Miller-Shettleworth model. Experiment 1 replicated previous findings that humans transfer navigational behavior, based on local geometric cues, from a rectangle-shaped environment to a kite-shaped environment, and vice versa. In Experiments 2 and 3, it was observed that learning about non-geometric cues blocked, and were blocked by, learning about local geometric cues. The reciprocal blocking observed is consistent with associative theories of spatial learning; however, it is difficult to explain the observed effects with theories of global-shape encoding in their current form.

Visuo-tactile integration in autism: atypical temporal binding may underlie greater reliance on proprioceptive information.

BACKGROUND: Evidence indicates that social functioning deficits and sensory sensitivities in autism spectrum disorder (ASD) are related to atypical sensory integration. The exact mechanisms underlying these integration difficulties are unknown; however, two leading accounts are (1) an over-reliance on proprioception and (2) atypical visuo-tactile temporal binding. We directly tested these theories by selectively manipulating proprioceptive alignment and visuo-tactile synchrony to assess the extent that these impact upon body ownership. METHODS: Children with ASD and typically developing controls placed their hand into a multisensory illusion apparatus, which presented two, identical live video images of their own hand in the same plane as their actual hand. One virtual hand was aligned proprioceptively with the actual hand (the veridical hand), and the other was displaced to the left or right. While a brushstroke was applied to the participants' actual (hidden) hand, they observed the two virtual images of their hand also being stroked and were asked to identify their real hand. During brushing, one of three different temporal delays was applied to either the displaced hand or the veridical hand. Thus, only one virtual hand had synchronous visuo-tactile inputs. RESULTS: Results showed that visuo-tactile synchrony overrides incongruent proprioceptive inputs in typically developing children but not in autistic children. Evidence for both temporally extended visuo-tactile binding and a greater reliance on proprioception are discussed. CONCLUSIONS: This is the first study to provide definitive evidence for temporally extended visuo-tactile binding in ASD. This may result in reduced processing of amodal inputs (i.e. temporal synchrony) over modal-specific information (i.e. proprioception). This would likely lead to failures in appropriately binding information from related events, which would impact upon sensitivity to sensory stimuli, body representation and social processes such as empathy and imitation.

The developmental trajectory of intramaze and extramaze landmark biases in spatial navigation: An unexpected journey.

Adults learning to navigate to a hidden goal within an enclosed space have been found to prefer information provided by the distal cues of an environment, as opposed to proximal landmarks within the environment. Studies with children, however, have shown that 5- or 7-year-olds do not display any preference toward distal or proximal cues during navigation. This suggests that a bias toward learning about distal cues occurs somewhere between the age of 7 years and adulthood. We recruited 5- to 11-year-old children and an adult sample to explore the developmental profile of this putative change. Across a series of 3 experiments, participants were required to navigate to a hidden goal in a virtual environment, the location of which was signaled by both extramaze and intramaze landmark cues. During testing, these cues were placed into conflict to assess the search preferences of participants. Consistent with previously reported findings, adults were biased toward using extramaze information. However, analysis of the data from children, which incorporated age as a continuous variable, suggested that older children in our sample were, in fact, biased toward using the intramaze landmark in our task. These findings suggest the bias toward using distal cues in spatial navigation, frequently displayed by adults, may be a comparatively late developing trait, and one that could supersede an initial developmental preference for proximal landmarks.

Spatial navigation in autism spectrum disorders: a critical review.

On the basis of relative strengths that have been attributed to the autistic cognitive profile, it has been suggested by a number of theorists that people with autism spectrum disorders (ASD) excel at spatial navigational tasks. However, many of these claims have been made in the absence of a close inspection of extant data in the scientific literature, let alone anecdotal reports of daily navigational experiences. The present review gathers together published studies that have attempted to explicitly address functional components of navigation in ASD populations, including assays of wayfinding, large-scale search, and path integration. This inspection reveals a pattern of apparent strengths and weaknesses in navigational abilities, thus illustrating the necessity for a more measured and comprehensive approach to the understanding of spatial behavior in ASD.

Learned predictiveness training modulates biases towards using boundary or landmark cues during navigation.

A number of navigational theories state that learning about landmark information should not interfere with learning about shape information provided by the boundary walls of an environment. A common test of such theories has been to assess whether landmark information will overshadow, or restrict, learning about shape information. Whilst a number of studies have shown that landmarks are not able to overshadow learning about shape information, some have shown that landmarks can, in fact, overshadow learning about shape information. Given the continued importance of theories that grant the shape information that is provided by the boundary of an environment a special status during learning, the experiments presented here were designed to assess whether the relative salience of shape and landmark information could account for the discrepant results of overshadowing studies. In Experiment 1, participants were first trained that either the landmarks within an arena (landmark-relevant), or the shape information provided by the boundary walls of an arena (shape-relevant), were relevant to finding a hidden goal. In a subsequent stage, when novel landmark and shape information were made relevant to finding the hidden goal, landmarks dominated behaviour for those given landmark-relevant training, whereas shape information dominated behaviour for those given shape-relevant training. Experiment 2, which was conducted without prior relevance training, revealed that the landmark cues, unconditionally, dominated behaviour in our task. The results of the present experiments, and the conflicting results from previous overshadowing experiments, are explained in terms of associative models that incorporate an attention variant.