► We review evidence for the Premotor theory of attention. ► Contrary to Premotor theory, compelling converging evidence indicates that endogenous attention and motor control are independent. ► There ...is reliable evidence that exogenous attention is dependant on oculomotor control. ► Premotor theory is not consistent with empirical data and should be rejected.
Spatial attention and eye-movements are tightly coupled, but the precise nature of this coupling is controversial. The influential but controversial Premotor theory of attention makes four specific predictions about the relationship between motor preparation and spatial attention. Firstly, spatial attention and motor preparation use the same neural substrates. Secondly, spatial attention is functionally equivalent to planning goal directed actions such as eye-movements (i.e. planning an action is both necessary and sufficient for a shift of spatial attention). Thirdly, planning a goal directed action with any effector system is sufficient to trigger a shift of spatial attention. Fourthly, the eye-movement system has a privileged role in orienting visual spatial attention. This article reviews empirical studies that have tested these predictions. Contrary to predictions one and two there is evidence of anatomical and functional dissociations between endogenous spatial attention and motor preparation. However, there is compelling evidence that exogenous attention is reliant on activation of the oculomotor system. With respect to the third prediction, there is correlational evidence that spatial attention is directed to the endpoint of goal-directed actions but no direct evidence that this attention shift is dependent on motor preparation. The few studies to have directly tested the fourth prediction have produced conflicting results, so the extent to which the oculomotor system has a privileged role in spatial attention remains unclear. Overall, the evidence is not consistent with the view that spatial attention is functionally equivalent to motor preparation so the Premotor theory should be rejected, although a limited version of the Premotor theory in which only exogenous attention is dependent on motor preparation may still be tenable. A plausible alternative account is that activity in the motor system contributes to biased competition between different sensory representations with the winner of the competition becoming the attended item.
Congenital Prosopagnosia (CP) is an innate impairment in face perception with heterogeneous characteristics. It is still unclear if and to what degree holistic processing of faces is disrupted in CP. ...Such disruption would be expected to lead to a focus on local features of the face. In this study, we used binocular rivalry (BR) to implicitly measure face perception in conditions that favour holistic or local processing. The underlying assumption is that if stimulus saliency affects the perceptual dominance of a given stimulus in BR, one can deduce how salient a stimulus is for a given group (here: participants with and without CP) based on the measured perceptual dominance. A further open question is whether the deficit in face processing in CP extends to the processing of the facial display of emotions. In experiment 1, we compared predominance of upright and inverted faces displaying different emotions (fearful, happy, neutral) vs. houses between participants with CP (N = 21) and with normal face perception (N = 21). The results suggest that CP observers process emotions in faces automatically but rely more on local features than controls. The inversion of faces, which is supposed to disturb holistic processing, affected controls in a more pronounced way than participants with CP. In experiment 2, we introduced the Thatcher effect in BR by inverting the eye and mouth regions of the presented faces in the hope of further increasing the effect of face inversion. However, our expectations were not borne out by the results. Critically, both experiments showed that inversion effects were more pronounced in controls than in CP, suggesting that holistic face processing is less relevant in CP. We find BR to be a useful implicit test for assessing visual processing specificities in neurological participants.
Patients with spatial neglect show an ipsilesional exploration bias. We developed a gaze-contingent intervention that aims at reducing this bias and tested its effects on visual exploration in ...healthy participants: During a visual search, stimuli in one half of the search display are removed when the gaze moves into this half. This leads to a relative increase in the exploration of the other half of the search display – the one that can be explored without impediments. In the first experiment, we tested whether this effect transferred to visual exploration during a change detection task (under change blindness conditions), which was the case. In a second experiment, we modified the intervention (to an intermittent application) but the original version yielded more promising results. Thus, in the third experiment, the original version was used to test the longevity of its effects and whether its repeated application produced even stronger results. To this aim, we compared two groups: the first group received the intervention once, the second group repeatedly on three consecutive days. The change detection task was administered before the intervention and at four points in time after the last intervention (directly afterwards, + 1 hour, + 1 day, and +4 days). The results showed long-lasting effects of the intervention, most pronounced in the second group. Here the intervention changed the bias in the visual exploration pattern significantly until the last follow-up. We conclude that the intervention shows promise for the successful application in neglect patients.
Purpose
Hemophagocytic lymphohistiocytosis (HLH) is a severe hyperinflammatory syndrome emerging from a deregulated immune response due to various triggers. In adults, systematic data are sparse, ...which is why recommendations on diagnosis and management have been adopted from pediatric guidelines. A nationwide clinical registry with associated consulting service as collaborative initiative of HLH-specialized pediatricians and hematologists was initiated to better characterize HLH in adults.
Methods
Patients with proven or suspected HLH were registered by 44 institutions. Both HLH-2004 diagnostic criteria and the HScore (
www.saintantoine.aphp.fr/score/
) were used to confirm HLH diagnosis. Data referring to underlying disease, treatment, outcome, clinical presentation and laboratory findings were recorded.
Results
The study included 137 patients and provides the first systematic data on adult HLH in Germany. Median age was 50 years with a wide range (17–87 years), 87 patients (63.5%) were male. Most common triggering diseases were infections in 61 patients (44.5%) and malignancies in 48 patients (35%). Virtually all patients had elevated ferritin concentrations, and 74% had peak concentrations greater than 10,000 µg/l. At time of analysis, 67 of 131 patients (51%) had died. Patients with malignancy-associated HLH had the shortest median survival (160 days), however no statistically significant difference between subgroups was observed (
p
= 0.077). Platelets under 20*10
9
/l and low albumin concentrations (< 20 g/l) were associated with poor overall and 30-day survival.
Conclusion
Close multidisciplinary case consultation and cooperation is mandatory when treating adult HLH patients. Early contact with reference centers is recommended, especially in relapsing or refractory disease.
Hemophagocytic lymphohistiocytosis (HLH) is a rare though often fatal hyperinflammatory syndrome mimicking sepsis in the critically ill. Diagnosis relies on the HLH-2004 criteria and HScore, both of ...which have been developed in pediatric or adult non-critically ill patients, respectively. Therefore, we aimed to determine the sensitivity and specificity of HLH-2004 criteria and HScore in a cohort of adult critically ill patients.
In this further analysis of a retrospective observational study, patients ≥ 18 years admitted to at least one adult ICU at Charité - Universitätsmedizin Berlin between January 2006 and August 2018 with hyperferritinemia of ≥ 500 μg/L were included. Patients' charts were reviewed for clinically diagnosed or suspected HLH. Receiver operating characteristics (ROC) analysis was performed to determine prediction accuracy.
In total, 2623 patients with hyperferritinemia were included, of whom 40 patients had HLH. We found the best prediction accuracy of HLH diagnosis for a cutoff of 4 fulfilled HLH-2004 criteria (95.0% sensitivity and 93.6% specificity) and HScore cutoff of 168 (100% sensitivity and 94.1% specificity). By adjusting HLH-2004 criteria cutoffs of both hyperferritinemia to 3000 μg/L and fever to 38.2 °C, sensitivity and specificity increased to 97.5% and 96.1%, respectively. Both a higher number of fulfilled HLH-2004 criteria OR 1.513 (95% CI 1.372-1.667); p < 0.001 and a higher HScore OR 1.011 (95% CI 1.009-1.013); p < 0.001 were significantly associated with in-hospital mortality.
An HScore cutoff of 168 revealed a sensitivity of 100% and a specificity of 94.1%, thereby providing slightly superior diagnostic accuracy compared to HLH-2004 criteria. Both HLH-2004 criteria and HScore proved to be of good diagnostic accuracy and consequently might be used for HLH diagnosis in critically ill patients.
The study was registered with www.ClinicalTrials.gov (NCT02854943) on August 1, 2016.
Cold agglutinin disease is a difficult-to-treat autoimmune hemolytic anemia in which immunoglobulin M antibodies bind to erythrocytes and fix complement, resulting in predominantly extravascular ...hemolysis. This trial tested the hypothesis that the anti-C1s antibody sutimlimab would ameliorate hemolytic anemia. Ten patients with cold agglutinin disease participated in the phase 1b component of a first-in-human trial. Patients received a test dose of 10-mg/kg sutimlimab followed by a full dose of 60 mg/kg 1 to 4 days later and 3 additional weekly doses of 60 mg/kg. All infusions were well tolerated without premedication. No drug-related serious adverse events were observed. Seven of 10 patients with cold agglutinin disease responded with a hemoglobin increase >2 g/dL. Sutimlimab rapidly increased hemoglobin levels by a median of 1.6 g/dL within the first week, and by a median of 3.9 g/dL (interquartile range, 1.3-4.5 g/dL; 95% confidence interval, 2.1-4.5) within 6 weeks (P = .005). Sutimlimab rapidly abrogated extravascular hemolysis, normalizing bilirubin levels within 24 hours in most patients and normalizing haptoglobin levels in 4 patients within 1 week. Hemolytic anemia recurred when drug levels were cleared from the circulation 3 to 4 weeks after the last dose of sutimlimab. Reexposure to sutimlimab in a named patient program recapitulated the control of hemolytic anemia. All 6 previously transfused patients became transfusion-free during treatment. Sutimlimab was safe, well tolerated, and rapidly stopped C1s complement–mediated hemolysis in patients with cold agglutinin disease, significantly increasing hemoglobin levels and precluding the need for transfusions. This trial was registered at www.clinicaltrials.gov as #NCT02502903.
•Seven of 10 patients with cold agglutinin disease responded to the anti-C1s antibody with a median 4-g/dL increase in hemoglobin levels.•Upstream inhibition of the classical complement cascade is an effective treatment for patients with cold agglutinin disease.
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In the present study, we examined the extent of interference between a cognitive task (auditory n-back task) and different aspects of motor performance. Specifically, we wanted to find out whether ...such interference is more pronounced for aspects of planning as compared to programming. Here, motor planning is represented by a phenomenon called the “end-state comfort effect”, the fact that we tolerate uncomfortable initial postures in favour of a more comfortable final posture. We asked participants to grasp differently sized cylindrical objects and to place them on target platforms of varying height (grasp-and-place task), So, participants were required to (1) adjust their hand opening to the object width (action programming) and (2) to plan whether to grasp the object higher or lower in order to be able to place it comfortably onto the low or high target platform. We found that participants demonstrated the end-state comfort effect by anticipating the final posture und planning the movement accordingly with a higher object-grasp for low end-target position and lower object-grasp height for high end-target position, respectively. The auditory task was negatively affected by having to perform a visuomotor task in parallel, suggesting that the two tasks share cognitive and attentional resources. No significant impact from the auditory task on the motor tasks was found. Accordingly, it was not possible to determine which of the two motor aspects (programming or planning) contributed more towards the interference observed in the auditory task. To address this question, we carried out a second experiment. For this second experiment we focussed on the interference effects found in the auditory task and contrasted two versions of the grasp-and-place task. In the first version of the task, the height of the target-shelf varied from trial-to-trial but the width of the target object remained the same. We assumed that this version had high planning demands and low programming demands. In the second version the width of the target object varied and the target-shelf height remained constant. Presumably this increased programming demands but reduced planning demands. Significant interference with the auditory task was only found for the first version, supporting the hypothesis that motor planning requires more cognitive resources and thus creates higher multitasking costs.
Dual-task paradigms are procedures for investigating interference with two tasks performed simultaneously. Studies that previously addressed dual-task paradigms within a visuomotor reaching task ...yielded mixed results. While some of the studies found evidence of cognitive interference, called dual-task costs, other studies did not. We assume that dual-task costs only manifest themselves within the explicit component of adaptation, as it involves cognitive resources for processing. We suspect the divergent findings to be due to the lack of differentiation between the explicit and implicit component. In this study, we aimed to investigate how a cognitive secondary task affects visuomotor adaptation overall and its different components, both during and after adaptation. In a series of posttests, we examined the explicit and implicit components separately. Eighty participants performed a center-outward reaching movement with a 30° cursor perturbation. Participants were either assigned to a single task group (ST) or a dual-task group (DT) with an additional auditory 1-back task. To further enhance our predicted effect of dual-task interference on the explicit component, we added a visual feedback delay condition to both groups (ST/DTDEL). In the other condition, participants received visual feedback immediately after movement termination (ST/DTNoDEL).
While there were clear dual-task costs during the practice phase, there were no dual-task effects on any of the posttest measures. On one hand, our findings suggest that dual-task costs in visuomotor adaptation tasks can occur with sufficient cognitive demand, and on the other hand, that cognitive constraints may affect motor performance but not necessarily motor adaptation.
Goodale et al. (1991) reported a striking dissociation between vision for perception and action. They examined DF, a human patient who had damage to her ventral visual stream and suffered from visual ...form agnosia. She was unable to perceive an object's size but could match the opening of her hand to the object's size during grasping. It was concluded that grasping relied on a separate representation of visual size in the dorsal stream and required no visual input from the ventral stream. This observation inspired the influential perception-action model, which claimed separate visual streams for perception and action. However, in grasping (but not in corresponding perceptual tasks), participants receive haptic feedback after each trial. Using this feedback, DF might compensate for her impaired size-vision. I reexamined DF's grasping behavior using a mirror apparatus to dissociate the image of an object from its physical presence. DF's grasping was only normal when she received haptic feedback. Thus, in grasping, DF can rely on haptic feedback to compensate for her deficit in size-perception. This can explain why her grasping is significantly better than her perceptual performance. The findings emphasize the extent of early interstream interactions and highlight the multimodal nature of sensory processing in the dorsal stream.
Human parvovirus B19 has been linked to a variety of cardiac diseases, as well as to erythema infectiosum, acute arthropathy, and fetal hydrops. A causal association between viral infection and ...cardiac disease was frequently postulated following the detection of B19 DNA by PCR in endomyocardial biopsy specimens. Since the lifelong persistence of B19 DNA in bone marrow, skin, synovia, tonsils, and liver was previously reported, the aim of our study was to investigate the possibility of asymptomatic B19 DNA persistence in heart tissue. Myocardial autopsy and postmortem blood samples were prospectively collected from 69 bodies sent to the Department of Forensic Medicine, Freiburg University Medical Center, for inquests. All study subjects were screened for B19-specific antibodies using a commercial enzyme immunoassay. Tissue samples were analyzed by real-time PCR for the presence of viral DNA. Since the presence of B19 genotype 2, known to have been circulating before 1960, would prove long-lasting persistence, the presence of the B19 genotype was retrospectively determined in seven of the study subjects by melting temperature analysis and sequencing of the PCR product. B19 DNA was found in myocardial samples from 46 of 48 seropositive and in none of 21 seronegative individuals. B19 genotype 1 was found in three patients born between 1950 and 1969. Genotype 2 was found in four patients born between 1927 and 1957. Our findings suggest lifelong persistence of B19 DNA in heart tissue. Thus, the detection of B19 DNA in myocardial biopsy specimens alone is not sufficient to postulate a relationship between B19 infection and cardiac disease.
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