The neuroanatomy of visual extinction following right hemisphere brain damage: Insights from multivariate and Bayesian lesion analyses in acute stroke.

Multi-target attention, that is, the ability to attend and respond to multiple visual targets presented simultaneously on the horizontal meridian across both visual fields, is essential for everyday real-world behaviour. Given the close link between the neuropsychological deficit of extinction and attentional limits in healthy subjects, investigating the anatomy that underlies extinction is uniquely capable of providing important insights concerning the anatomy critical for normal multi-target attention. Previous studies into the brain areas critical for multi-target attention and its failure in extinction patients have, however, produced heterogeneous results. In the current study, we used multivariate and Bayesian lesion analysis approaches to investigate the anatomical substrate of visual extinction in a large sample of 108 acute right hemisphere stroke patients. The use of acute stroke patient data and multivariate/Bayesian lesion analysis approaches allowed us to address limitations associated with previous studies and so obtain a more complete picture of the functional network associated with visual extinction. Our results demonstrate that the right temporo-parietal junction (TPJ) is critically associated with visual extinction. The Bayesian lesion analysis additionally implicated the right intraparietal sulcus (IPS), in line with the results of studies in neurologically healthy participants that highlighted the IPS as the area critical for multi-target attention. Our findings resolve the seemingly conflicting previous findings, and emphasise the urgent need for further research to clarify the precise cognitive role of the right TPJ in multi-target attention and its failure in extinction patients.

Spatial neglect in the digital age: Influence of presentation format on patients' test behavior.

OBJECTIVE: Computerized neglect tests could significantly deepen our disorder-specific knowledge by effortlessly providing additional behavioral markers that are hardly or not extractable from existing paper-and-pencil versions. This study investigated how testing format (paper versus digital), and screen size (small, medium, large) affect the Center of cancelation (CoC) in right-hemispheric stroke patients in the Letters and the Bells cancelation task. Our second objective was to determine whether a machine learning approach could reliably classify patients with and without neglect based on their search speed, search distance, and search strategy. METHOD: We compared the CoC measure of right hemisphere stroke patients with neglect in two cancelation tasks across different formats and display sizes. In addition, we evaluated whether three additional parameters of search behavior that became available through digitization are neglect-specific behavioral markers. RESULTS: Patients' CoC was not affected by test format or screen size. Additional search parameters demonstrated lower search speed, increased search distance, and a more strategic search for neglect patients than for control patients without neglect. CONCLUSION: The CoC seems robust to both test digitization and display size adaptations. Machine learning classification based on the additional variables derived from computerized tests succeeded in distinguishing stroke patients with spatial neglect from those without. The investigated additional variables have the potential to aid in neglect diagnosis, in particular when the CoC cannot be validly assessed (e.g., when the test is not performed to completion).

The amnestic syndrome of posterior cerebral artery infarction.

BACKGROUND AND PURPOSE: Little is known about the character and underlying lesions of ischaemic amnesia. Episodic memory functions and brain lesions were therefore studied in 84 patients with acute ischaemic infarcts in the supply territory of the posterior cerebral artery. The aim was also to learn how the neural memory systems are organized. METHODS: Standard neuropsychological tests were used to assess verbal and figural memory. Patients were split into memory-impaired and memory-intact groups. Lesions were demarcated, normalized and anatomically labelled, using standard mapping procedures. RESULTS: Of the 84 patients more than 80% had an amnestic syndrome, mostly with combined memory impairment, less often with figural or verbal memory impairment. Amnesia in subjects with left hemispheric lesions was more frequent and more severe, with significantly lower scores on the verbal memory test. Normal performance or figural amnesia were prevalent after right hemispheric lesions. However, no amnesia subtype was strictly tied to left- or right-sided brain damage. Hippocampal and thalamic lesions were common, but 30% of lesions were extrahippocampal located in the ventral occipito-temporal cortex and long occipital white matter tracts. Most amnestic patients lacked awareness for their memory impairment. CONCLUSIONS: Memory impairment is a key clinical manifestation of acute posterior cerebral artery stroke. Amnesia is more frequent and more severe after left stroke, suggesting a left hemisphere dominance of the two memory systems. Domain specific memory appears not to be strictly lateralized, since deficits in verbal and figural memory were found after lesions of both sides. Extrahippocampal lesions may also cause memory impairment.

Temporo-parietal brain regions are involved in higher order object perception.

Lesions to posterior temporo-parietal brain regions are associated with deficits in perception of global, hierarchical shapes, but also with impairments in the processing of objects presented under demanding viewing conditions. Evidence from neuroimaging studies and lesion patterns observed in patients with simultanagnosia and agnosia for object orientation suggest similar brain regions to be involved in perception of global shapes and processing of objects in atypical ('non-canonical') orientation. In a localizer experiment, we identified individual temporo-parietal brain areas involved in global shape perception and found significantly higher BOLD signals during the processing of non-canonical compared to canonical objects. In a multivariate approach, we demonstrated that posterior temporo-parietal brain areas show distinct voxel patterns for non-canonical and canonical objects and that voxel patterns of global shapes are more similar to those of objects in non-canonical compared to canonical viewing conditions. These results suggest that temporo-parietal brain areas are not only involved in global shape perception but might serve a more general mechanism of complex object perception. Our results challenge a strict attribution of object processing to the ventral visual stream by suggesting specific dorsal contributions in more demanding viewing conditions.

The effects of audits and fines on upcoding in neonatology.

Upcoding is a common type of fraud in healthcare. However, how audit policies need to be designed to cope with upcoding is not well understood. We provide causal evidence on the effect of random audits with different probabilities and financial consequences. Using a controlled laboratory experiment, we mimic the decision situation of obstetrics staff members to report birth weights of neonatal infants. Subjects' payments in the experiment depend on their reported birth weights and follow the German non-linear diagnosis-related group remuneration for neonatal care. Our results show that audits with low detection probabilities only reduce fraudulent birth-weight reporting, when they are coupled with fines for fraudulent reporting. For audit policies with fines, increasing the probability of an audit only effectively enhances honest reporting, when switching from detectable to less gainful undetectable upcoding is not feasible. Implications for audit policies are discussed.

Using machine learning-based lesion behavior mapping to identify anatomical networks of cognitive dysfunction: Spatial neglect and attention.

Previous lesion behavior studies primarily used univariate lesion behavior mapping techniques to map the anatomical basis of spatial neglect after right brain damage. These studies led to inconsistent results and lively controversies. Given these inconsistencies, the idea of a wide-spread network that might underlie spatial orientation and neglect has been pushed forward. In such case, univariate lesion behavior mapping methods might have been inherently limited in detecting the presumed network due to limited statistical power. By comparing various univariate analyses with multivariate lesion-mapping based on support vector regression, we aimed to validate the network hypothesis directly in a large sample of 203 newly recruited right brain damaged patients. If the exact same correction factors and parameter combinations (FDR correction and dTLVC for lesion size control) were used, both univariate as well as multivariate approaches uncovered the same complex network pattern underlying spatial neglect. At the cortical level, lesion location dominantly affected the temporal cortex and its borders into inferior parietal and occipital cortices. Beyond, frontal and subcortical gray matter regions as well as white matter tracts connecting these regions were affected. Our findings underline the importance of a right network in spatial exploration and attention and specifically in the emergence of the core symptoms of spatial neglect.

An empirical evaluation of multivariate lesion behaviour mapping using support vector regression.

Multivariate lesion behaviour mapping based on machine learning algorithms has recently been suggested to complement the methods of anatomo-behavioural approaches in cognitive neuroscience. Several studies applied and validated support vector regression-based lesion symptom mapping (SVR-LSM) to map anatomo-behavioural relations. However, this promising method, as well as the multivariate approach per se, still bears many open questions. By using large lesion samples in three simulation experiments, the present study empirically tested the validity of several methodological aspects. We found that (i) correction for multiple comparisons is required in the current implementation of SVR-LSM, (ii) that sample sizes of at least 100-120 subjects are required to optimally model voxel-wise lesion location in SVR-LSM, and (iii) that SVR-LSM is susceptible to misplacement of statistical topographies along the brain's vasculature to a similar extent as mass-univariate analyses.

Dishonesty in health care practice: A behavioral experiment on upcoding in neonatology.

Dishonest behavior significantly increases the cost of medical care provision. Upcoding of patients is a common form of fraud to attract higher reimbursements. Imposing audit mechanisms including fines to curtail upcoding is widely discussed among health care policy-makers. How audits and fines affect individual health care providers' behavior is empirically not well understood. To provide new evidence on fraudulent behavior in health care, we analyze the effect of a random audit including fines on individuals' honesty by means of a novel controlled behavioral experiment framed in a neonatal care context. Prevalent dishonest behavior declines significantly when audits and fines are introduced. The effect is driven by a reduction in upcoding when being detectable. Yet upcoding increases when not being detectable as fraudulent. We find evidence that individual characteristics (gender, medical background, and integrity) are related to dishonest behavior. Policy implications are discussed.

The Effects of Introducing Mixed Payment Systems for Physicians: Experimental Evidence.

Mixed payment systems have become a prominent alternative to paying physicians through fee-for-service and capitation. While theory shows mixed payment systems to be superior, causal effects on physicians' behavior when introducing mixed systems are not well understood empirically. We systematically analyze the influence of fee-for-service, capitation, and mixed payment systems on physicians' service provision. In a controlled laboratory setting, we implement an exogenous variation of the payment method. Medical and non-medical students in the role of physicians in the lab (N = 213) choose quantities of medical services affecting patients' health outside the lab. Behavioral data reveal significant overprovision of medical services under fee-for-service and significant underprovision under capitation, although less than predicted when assuming profit maximization. Introducing mixed payment systems significantly reduces deviations from patient-optimal treatment. Although medical students tend to be more patient regarding, our results hold for both medical and non-medical students. Responses to incentive systems can be explained by a behavioral model capturing individual altruism. In particular, we find support that altruism plays a role in service provision and can partially mitigate agency problems, but altruism is heterogeneous in the population. Copyright © 2015 John Wiley & Sons, Ltd.

A new look at physicians' responses to financial incentives: Quality of care, practice characteristics, and motivations.

There is considerable controversy about what causes (in)effectiveness of physician performance pay in improving the quality of care. Using a behavioral experiment with German primary-care physicians, we study the incentive effect of performance pay on service provision and quality of care. To explore whether variations in quality are based on the incentive scheme and the interplay with physicians' real-world profit orientation and patient-regarding motivations, we link administrative data on practice characteristics and survey data on physicians' attitudes with experimental data. We find that, under performance pay, quality increases by about 7pp compared to baseline capitation. While the effect increases with the severity of illness, the bonus level does not significantly affect the quality of care. Data linkage indicates that primary-care physicians in high-profit practices provide a lower quality of care. Physicians' other-regarding motivations and attitudes are significant drivers of high treatment quality.

Changing preferences: An experiment and estimation of market-incentive effects on altruism.

This paper studies how altruistic preferences are changed by markets and incentives. We conduct a laboratory experiment with a within-subject design. Subjects are asked to choose health care qualities for hypothetical patients in monopoly, duopoly, and quadropoly. Prices, costs, and patient benefits are experimental incentive parameters. In monopoly, subjects choose quality by trading off between profits and altruistic patient benefits. In duopoly and quadropoly, subjects play a simultaneous-move game. Uncertain about an opponent's altruism, each subject competes for patients by choosing qualities. Bayes-Nash equilibria describe subjects' quality decisions as functions of altruism. Using a nonparametric method, we estimate the population altruism distributions from Bayes-Nash equilibrium qualities in different markets and incentive configurations. Competition tends to reduce altruism, but duopoly and quadropoly equilibrium qualities are much higher than monopoly. Although markets crowd out altruism, the disciplinary powers of market competition are stronger. Counterfactuals confirm markets change preferences.

The formation of physician altruism.

We study how patient-regarding altruism is formed by medical education. We elicit and structurally estimate altruistic preferences using experimental data from a large sample of medical students (N = 733) in Germany at different progress stages in their studies. The estimates reveal substantial heterogeneity in altruistic preferences of medical students. Patient-regarding altruism is highest for freshmen, significantly declines for students in the course of medical studies, and tends to increase again for last year students, who assist in clinical practice. Also, patient-regarding altruism is higher for females and positively associated to general altruism. Altruistic medical students have gained prior practical experience in healthcare, have lower income expectations, and are more likely to choose surgery and pediatrics as their preferred specialty.

Behavioral Economics Interventions to Improve Medical Decision-Making.

BACKGROUND: In medicine, a wide gap exists between the medical care that ought to be possible in the light of the current state of medical research and the care that is actually provided. Behavioral biases and noise are two major reasons for this. METHODS: We present the findings of a selective literature review and illustrate how interventions based on behavioral economics can help physicians make better decisions and thereby improve treatment outcomes. RESULTS: A number of behavioral economics interventions, making use of, for example, default settings, active decision rules, social norms, and self-commitments, may improve physicians' clinical decision-making. Evidence on long-term effects is, however, mostly lacking. CONCLUSION: Despite their apparent potential, the application of behavioral economic interventions to improve medical decisionmaking is still in its infancy, particularly in Germany.

Disconnectomics to unravel the network underlying deficits of spatial exploration and attention.

Spatial attention and exploration are related to a predominantly right hemispheric network structure. However, the areas of the brain involved and their exact role is still debated. Spatial neglect following right hemispheric stroke lesions has been frequently viewed as a model to study these processes in humans. Previous investigations on the anatomical basis on spatial neglect predominantly focused on focal brain damage and lesion-behaviour mapping analyses. This approach might not be suited to detect remote areas structurally spared but which might contribute to the behavioural deficit. In the present study of a sample of 203 right hemispheric stroke patients, we combined connectome lesion-symptom mapping with multivariate support vector regression to unravel the complex and disconnected network structure in spatial neglect. We delineated three central nodes that were extensively disconnected from other intrahemispheric areas, namely the right superior parietal lobule, the insula, and the temporal pole. Additionally, the analysis allocated central roles within this network to the inferior frontal gyrus (pars triangularis and opercularis), right middle temporal gyrus, right temporal pole and left and right orbitofrontal cortices, including interhemispheric disconnection. Our results suggest that these structures-although not necessarily directly damaged-might play a role within the network underlying spatial neglect in humans.

Mapping the human praxis network: an investigation of white matter disconnection in limb apraxia of gesture production.

Left hemispheric cerebral stroke can cause apraxia, a motor cognitive disorder characterized by deficits of higher-order motor skills such as the failure to accurately produce meaningful gestures. This disorder provides unique insights into the anatomical and cognitive architecture of the human praxis system. The present study aimed to map the structural brain network that is damaged in apraxia. We assessed the ability to perform meaningful gestures with the hand in 101 patients with chronic left hemisphere stroke. Structural white matter fibre damage was directly assessed by diffusion tensor imaging and fractional anisotropy mapping. We used multivariate topographical inference on tract-based fractional anisotropy topographies to identify white matter disconnection associated with apraxia. We found relevant pathological white matter alterations in a densely connected fronto-temporo-parietal network of short and long association fibres. Hence, the findings suggest that heterogeneous topographical results in previous lesion mapping studies might not only result from differences in study design, but also from the general methodological limitations of univariate topographical mapping in uncovering the structural praxis network. A striking role of middle and superior temporal lobe disconnection, including temporo-temporal short association fibres, was found, suggesting strong involvement of the temporal lobe in the praxis network. Further, the results stressed the importance of subcortical disconnections for the emergence of apractic symptoms. Our study provides a fine-grain view into the structural connectivity of the human praxis network and suggests a potential value of disconnection measures in the clinical prediction of behavioural post-stroke outcome.

Lying in a 3T MRI scanner induces neglect-like spatial attention bias.

The static magnetic field of MRI scanners can induce a magneto-hydrodynamic stimulation of the vestibular organ (MVS). In common fMRI settings, this MVS effect leads to a vestibular ocular reflex (VOR). We asked whether - beyond inducing a VOR - putting a healthy subject in a 3T MRI scanner would also alter goal-directed spatial behavior, as is known from other types of vestibular stimulation. We investigated 17 healthy volunteers, all of which exhibited a rightward VOR inside the MRI-scanner as compared to outside-MRI conditions. More importantly, when probing the distribution of overt spatial attention inside the MRI using a visual search task, subjects scanned a region of space that was significantly shifted toward the right. An additional estimate of subjective straight-ahead orientation likewise exhibited a rightward shift. Hence, putting subjects in a 3T MRI-scanner elicits MVS-induced horizontal biases of spatial orienting and exploration, which closely mimic that of stroke patients with spatial neglect.

Disconnection somewhere down the line: Multivariate lesion-symptom mapping of the line bisection error.

Line Bisection is a simple task frequently used in stroke patients to diagnose disorders of spatial perception characterized by a directional bisection bias to the ipsilesional side. However, previous anatomical and behavioural findings are contradictory, and the diagnostic validity of the line bisection task has been challenged. We hereby aimed to re-analyse the anatomical basis of pathological line bisection by using multivariate lesion-symptom mapping and disconnection-symptom mapping based on support vector regression in a sample of 163 right hemispheric acute stroke patients. In line with some previous studies, we observed that pathological line bisection was related to more than a single focal lesion location. Cortical damage primarily to right parietal areas, particularly the inferior parietal lobe, including the angular gyrus, as well as damage to the right basal ganglia contributed to the pathology. In contrast to some previous studies, an involvement of frontal cortical brain areas in the line bisection task was not observed. Subcortically, damage to the right superior longitudinal fasciculus (I, II and III) and arcuate fasciculus as well as the internal capsule was associated with line bisection errors. Moreover, white matter damage of interhemispheric fibre bundles, such as the anterior commissure and posterior parts of the corpus callosum projecting into the left hemisphere, was predictive of pathological deviation in the line bisection task.

A network underlying human higher-order motor control: Insights from machine learning-based lesion-behaviour mapping in apraxia of pantomime.

Neurological patients with apraxia of pantomime provide us with a unique opportunity to study the neural correlates of higher-order motor function. Previous studies using lesion-behaviour mapping methods led to inconsistent anatomical results, reporting various lesion locations to induce this symptom. We hypothesised that the inconsistencies might arise from limitations of mass-univariate lesion-behaviour mapping approaches if our ability to pantomime the use of objects is organised in a brain network. Thus, we investigated apraxia of pantomime by using multivariate lesion behaviour mapping based both on support vector regression and sparse canonical correlations in a sample of 130 left-hemisphere stroke patients. Both multivariate methods identified multiple areas to underlie high-order motor control, including inferior parietal lobule, precentral gyrus, posterior parts of middle temporal cortex, and insula. Further, long association fibres were affected, such as the superior longitudinal fascicle, inferior occipito-frontal fascicle, uncinated fascicle, and superior occipito-frontal fascicle. The findings underline the benefits of multivariate lesion-behaviour mapping in brain networks and provide new insights into the brain networks underlying higher-order motor control.

The Effect of Expert Feedback on Antibiotic Prescribing in Pediatrics: Experimental Evidence.

Background. Inappropriate prescribing of antibiotics, which is common in pediatric care, is a key driver of antimicrobial resistance. To mitigate the development of resistance, antibiotic stewardship programs often suggest the inclusion of feedback targeted at individual providers. Empirically, however, it is not well understood how feedback affects individual physicians' antibiotic prescribing decisions. Also, the question of how physicians' characteristics, such as clinical experience, relate to antibiotic prescribing decisions and to responses to feedback is largely unexplored. Objective. To analyze the causal effect of descriptive expert feedback (and individual characteristics) on physicians' antibiotic prescribing decisions in pediatrics. Design. We employed a randomized, controlled framed field experiment, in which German pediatricians (n=73) decided on the length of first-line antibiotic treatment for routine pediatric cases. In the intervention group (n=39), pediatricians received descriptive feedback in form of an expert benchmark, which allowed them to compare their own prescribing decisions with expert recommendations. The recommendations were elicited in a survey of pediatric department directors (n=20), who stated the length of antibiotic therapies they would choose for the routine cases. Pediatricians' characteristics were elicited in a comprehensive questionnaire. Results. Providing pediatricians with expert feedback significantly reduced the length of antibiotic therapies by 10% on average. Also, the deviation of pediatricians' decisions from experts' recommendations significantly decreased. Antibiotic therapy decisions were significantly related to pediatricians' clinical experience, risk attitudes, and personality traits. The effect of feedback was significantly associated with physicians' experience. Conclusion. Our results indicate that descriptive expert feedback can be an effective means to guide pediatricians, especially those who are inexperienced, toward more appropriate antibiotic prescribing. Therefore, it seems to be suitable for inclusion in antibiotic stewardship programs.