Binocular rivalry reveals differential face processing in congenital prosopagnosia.

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.

Value of hemophagocytosis in the diagnosis of hemophagocytic lymphohistiocytosis in critically ill patients.

BACKGROUND: Ferritin is an established biomarker in the diagnosis of secondary hemophagocytic lymphohistiocytosis (HLH), which is diagnosed by the HLH-2004 criteria. Among these criteria, detection of hemophagocytosis through invasive procedures may delay early life saving treatment. Our aim was to investigate the value of hemophagocytosis in diagnosing HLH in critically ill patients. METHODS: In this secondary analysis of a retrospective observational study, we included all patients aged ≥18 years and admitted to any adult ICU at Charité-Universitätsmedizin Berlin between January 2006 and August 2018, who had hyperferritinemia (≥500 µg/L) and underwent bone marrow biopsy during their ICU course. RESULTS: Two hundred fifty-two patients were included, of whom 31 (12.3%) showed hemophagocytosis. In multivariable logistic regression analysis, maximum ferritin was independently associated with hemophagocytosis. By removing hemophagocytosis from HLH-2004 criteria and HScore, prediction accuracy for HLH diagnosis was only marginally decreased compared to the original scores. CONCLUSIONS: Our results strengthen the diagnostic value of ferritin and underline the importance of considering HLH diagnosis in patients with high ferritin but only four fulfilled HLH-2004 criteria, when hemophagocytosis was not assessed or not detectable. Proof of hemophagocytosis is not required for a reliable HLH diagnosis.

Lymphoma-associated hemophagocytic lymphohistiocytosis (LA-HLH): a scoping review unveils clinical and diagnostic patterns of a lymphoma subgroup with poor prognosis.

Hemophagocytic lymphohistiocytosis (HLH) is a severe hyperinflammatory syndrome driven by pathologic activation of cytotoxic T-lymphocytes and macrophages. Despite advances in diagnostics and management, adult patients with lymphoma-associated HLH (LA-HLH) harbor particularly poor prognosis and optimal treatment remains challenging. As systematic data on LA-HLH are scarce, we aimed to synthesize research evidence by thorough analysis of the published literature in PubMed (MEDLINE-database) within the context of a scoping review. Of 595 search results, 132 articles providing information on 542 patients were reviewed and analyzed. Median patient age was 60 years (range, 18-98) with male predominance (62.7%). B- and T-NHL were equally represented (45.6% and 45.2%), Hodgkin's lymphoma was reported in 8.9% of the cases. The majority of patients (91.6%) presented in Ann-Arbor-Stages III and IV, and bone marrow infiltration was observed in a significant proportion of patients (61.5%). Soluble CD25 levels were markedly elevated (median 10,000 U/ml), with levels beyond 10,000 U/ml indicating unfavorable prognosis for 30-day and overall survival. 66.8% of the patients died after median 5.1 months. LA-HLH remains a clinical challenge requiring specialized management. Timely diagnosis and appropriate lymphoma-specific treatment are of utmost importance to enhance patient outcomes.

The redundant target paradigm and its use as a blindsight-test: A meta-analytic study.

The redundant target effect (RTE) is the well-known effect whereby a single target is detected faster when a second, redundant target is presented simultaneously. The RTE was shown in different experimental designs and applied in various clinical contexts. However, there are also studies showing non-effects or effects in the opposite direction. Our meta-analysis aims to investigate the replicability of the RTE. Herein, we focused on the clinical context within which the RTE has been applied most often and for which it gained particular prominence: The research on blindsight and other forms of residual vision in patients with damage to the neuronal visual system. The application of the RTE in clinical contexts assumes that whenever vision is present, an RTE will be found. Put differently, the RTE as a tool to uncover residual vision presumes that the RTE is a consistent feature of vision in the healthy population. We found a significant summary effect size of the RTE in healthy participants. The effect size depended on certain experimental features: task type, target configuration in the redundant condition, and how reaction times were computed in the single condition. A specific feature combination is typically used in blindsight research. Analyzing studies with this feature combination revealed a significant summary effect size in healthy participants predicting positive RTEs for future studies. A power-analysis revealed a required sample size of 14 participants to obtain an RTE with high reliability. However, the required sample size is rarely reached in blindsight research. Rather, blindsight research is mostly based on single-case studies. In summary, the RTE is a robust effect on group level but does not occur in every single individual. This means failure to obtain an RTE in a single patient should not be interpreted as evidence for the absence of residual vision in this patient.

[Clinical examination of spatial neglect and other disorders of spatial cognition]. / Klinische Untersuchung des unilateralen Neglects und weiterer Störungen der Raumkognition.

Neglect occurring after stroke, neoplasms or degenerative processes can lead to considerable disability in everyday life as can other disorders of spatial orientation. Therefore, a dedicated examination and early diagnostic classification are obligatory. Behavioral tests are helpful in this respect, enabling the clinician to obtain an initial overview of the existing deficits even at the patient's bedside. The clinical (bedside) examination of spatial neglect as well as the corresponding differential diagnostic procedure for the clarification of (possibly additionally or exclusively existing) hemianopia and extinction, as well as the examination of disorders of visuospatial perception, visuoconstructive disorders, topographic disorders, Bálint's syndrome, simultanagnosia, and optic ataxia are presented. The presentation is based on the newly revised (year 2023) guidelines of the Association of the Scientific Medical Societies in Germany (AWMF) on this subject area.

The role of habitual learning in premotor attention allocation.

Dual-task studies have demonstrated that goal-directed actions are typically preceded by a premotor shift of visual attention toward the movement goal location. This finding is often taken as evidence for an obligatory coupling between attention and motor preparation. Here, we examined whether this coupling entails a habitual component relating to an expectation of spatial congruence between visual and motor targets. In two experiments, participants had to identify a visual discrimination target (DT) while preparing variably delayed pointing movements to a motor target (MT). To induce distinct expectations regarding the DT position, different groups of participants performed a training phase in which the DT either always appeared at MT, opposite to MT, or at an unpredictable position. In a subsequent test phase, the DT position was randomized to assess the impact of learned expectancy on premotor attention allocation. Although we applied individually determined DT presentation times in the test phase of Experiment 1, a fixed DT presentation time was used in Experiment 2. Both experiments yielded evidence for attentional enhancement at the expected DT position. Although interpretability of this effect was limited in Experiment 1 because of between-group differences in DT presentation time, results of Experiment 2 were much clearer. Specifically, a marked discrimination benefit was observed at the position opposite to MT in participants anticipating the DT at this position, whereas no statistically significant benefit was found at MT. Crucially, this was observed at short movement delays, demonstrating that expectation of spatial incongruence between visual and motor targets allows for decoupling of attentional resources from ongoing motor preparation. Based on our findings, we suggest that premotor attention shifts entail a considerable habitual component rather than being the sole result of motor programming.

Temporal order judgments and presaccadic shifts of attention: What can prior entry teach us about the premotor theory?

A temporal order judgment (TOJ) 2-alternative forced choice design was used to examine presaccadic shifts of attention. Prior work on the premotor theory of attention (PTA) has predominantly focused on single-target discrimination tasks as a tool to measure accuracy and shifts of attention. It is important to demonstrate that the PTA is effective across attentional tasks that have been shown to be reliable in other contexts. Therefore, it was decided to use a perceptual task that probes multiple locations simultaneously and can equally be used to examine spatial spread of attention in more detail. In typical TOJ studies, prior entry is the metric used to measure an attentional effect. Prior entry is the biasing of temporal perception toward an attentionally cued location. This generally manifests as observers processing events at the cued location more rapidly, altering their perspective of temporal order. Participants were required to prepare saccades toward one of four targets, two of which would light up either synchronously or sequentially after a GO signal but before saccadic execution. Results demonstrated that in conditions with critical stimulus onset asynchronies, saccade preparation had a significant effect on performance. Prior entry effects were observed at saccade congruent locations with probes at these locations being typically perceived earlier than probes presented at a neutral location. These effects were not observed in control trials without a saccade. A further spatial effect was demonstrated for the attentional modulation, suggesting that this effect is restricted predominantly to horizontal configurations. Overall, results demonstrated that presaccadic attention is effective at eliciting a prior entry effect in TOJ designs and that such effects are more pronounced when the probes are distributed across the two lateral hemifields.

Not Simply a Structural Problem: Psychological Determinants of Headache in Patients with Tumors of the Sellar Region.

OBJECTIVE: Headache in patients with tumors of the sellar region (TSR) has previously been attributed entirely to biomechanical causes. This study aimed to investigate the influence of psychological determinants for the occurrence of and disability due to headaches in patients with TSR. METHODS: This was a cross-sectional single-center study with a logistic regression approach. Eighty-four patients (75%) with pituitary adenomas and 28 with other TSR prior to first-time neurosurgery were investigated. One-hundred and twelve patients received standardized questionnaires on personality, headache characteristics, and disability due to headache. Fifty-nine patients additionally filled in questionnaires about coping with stress and pain catastrophizing. Separate logistic regression models were used to predict the risk of headache occurrence and disability due to headache by personality, stress coping, and pain catastrophizing. RESULTS: Conscientiousness, neuroticism, and pain catastrophizing were significant predictors of headache occurrence. The amount of explained variance for both models predicting headache occurrence was comparable to that in primary headache. Neuroticism, pain catastrophizing, and humor as a coping strategy predicted disability due to headache with a high variance explanation of 20-40%. CONCLUSION: For the first time, we report data supporting a strong psychological influence on headache and headache-related disability in patients with TSR, which argue against purely mechanistic explanatory models. Physicians treating patients with TSR and headaches should adopt an integrative diagnostic and treatment approach, taking the biopsychosocial model of pain into account.

ASXL1 mutations predict inferior molecular response to nilotinib treatment in chronic myeloid leukemia.

Gene mutations independent of BCR::ABL1 have been identified in newly diagnosed patients with chronic myeloid leukemia (CML) in chronic phase, whereby mutations in epigenetic modifier genes were most common. These findings prompted the systematic analysis of prevalence, dynamics, and prognostic significance of such mutations, in a clinically well-characterized patient population of 222 CML patients from the TIGER study (CML-V) by targeted next-generation sequencing covering 54 myeloid leukemia-associated genes. In total, 53/222 CML patients (24%) carried 60 mutations at diagnosis with ASXL1 being most commonly affected (n = 20). To study mutation dynamics, longitudinal deep sequencing analysis of serial samples was performed in 100 patients after 12, 24, and 36 months of therapy. Typical patterns of clonal evolution included eradication, persistence, and emergence of mutated clones. Patients carrying an ASXL1 mutation at diagnosis showed a less favorable molecular response to nilotinib treatment, as a major molecular response (MMR) was achieved less frequently at month 12, 18, and 24 compared to all other patients. Patients with ASXL1 mutations were also younger and more frequently found in the high risk category, suggesting a central role of clonal evolution associated with ASXL1 mutations in CML pathogenesis.

Dual-task interference in action programming and action planning - Evidence from the end-state comfort effect.

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.

How to test blindsight without light scatter artefacts?

light scatter artefacts are a methodological problem in testing residual visual capacities (RVCs), for instance blindsight, in patients with homonymous visual field defects (HVFDs). The term light scatter artefact describes the phenomenon that light from targets directed towards the HVFD can stray into the sighted visual field. This might enable an observer to respond correctly to information directed at her blind field despite the fact that she is unable to process that information in the blind field itself. In this manuscript, we present a review of the relevance of light scatter in visual neuroscience, discuss factors that influence the impact of light scatter and evaluate means to test for light scatter artefacts. Furthermore, we present findings from an empirical study that was aimed at developing tests for RVCs that are free of light scatter artefacts. Previous studies on light scatter only used small sample sizes and equipment that is no longer in use. Hence, their results cannot be generalized to future experiments making it necessary to run laborious light scatter tests for every new study on RVCs. To avoid this, we hereby start a pool of stimuli and paradigms which demonstrably do not elicit light scatter artefacts. To this end, we investigated 21 healthy young participants in three frequently used RVC-paradigms: (1) temporal 2AFC task, (2) movement direction discrimination, and (3) redundant target paradigm. For each paradigm, we applied the blind-spot method. But first, we had to establish that our testing paradigm was sufficiently sensitive to detect light scatter artefacts. For this, we used conditions that are known to produce strong light scatter and a paradigm that is very sensitive to such effects. Specifically, we presented white targets on a black background in a dark room. The stimuli were presented to observers' blind spot. To check for light scatter artefacts, we used a target-detection task in a temporal 2AFC format. We obtained clear light scatter artefacts. Participants produced reliably above-chance detection performance under these conditions. The other two luminance conditions, measured in an illuminated room, did not produce light scatter artefacts. Accuracy in the temporal 2AFC task was at chance level for white targets on a grey background at the blind-spot position. Additionally, black targets on a grey background avoided light scatter artefacts in all three RVC-paradigms. In future, researchers can apply these stimulus and illumination conditions when using one of the three above paradigms in their studies. Using these conditions, they will be able to avoid light scatter artefacts without having to perform their own blind-spot tests.

Exploring the effectiveness of auditory, visual, and audio-visual sensory cues in a multiple object tracking environment.

Maintaining object correspondence among multiple moving objects is an essential task of the perceptual system in many everyday life activities. A substantial body of research has confirmed that observers are able to track multiple target objects amongst identical distractors based only on their spatiotemporal information. However, naturalistic tasks typically involve the integration of information from more than one modality, and there is limited research investigating whether auditory and audio-visual cues improve tracking. In two experiments, we asked participants to track either five target objects or three versus five target objects amongst similarly indistinguishable distractor objects for 14 s. During the tracking interval, the target objects bounced occasionally against the boundary of a centralised orange circle. A visual cue, an auditory cue, neither or both coincided with these collisions. Following the motion interval, the participants were asked to indicate all target objects. Across both experiments and both set sizes, our results indicated that visual and auditory cues increased tracking accuracy although visual cues were more effective than auditory cues. Audio-visual cues, however, did not increase tracking performance beyond the level of purely visual cues for both high and low load conditions. We discuss the theoretical implications of our findings for multiple object tracking as well as for the principles of multisensory integration.

Additional cognitive load decreases performance but not adaptation to a visuomotor transformation.

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.

Differential Diagnosis of Hyperferritinemia in Critically Ill Patients.

BACKGROUND: Elevated serum ferritin is a common condition in critically ill patients. It is well known that hyperferritinemia constitutes a good biomarker for hemophagocytic lymphohistiocytosis (HLH) in critically ill patients. However, further differential diagnoses of hyperferritinemia in adult critically ill patients remain poorly investigated. We sought to systematically investigate hyperferritinemia in adult critically ill patients without HLH. METHODS: In this secondary analysis of a retrospective observational study, patients ≥18 years admitted to at least one adult intensive care unit at Charité-Universitätsmedizin Berlin between January 2006 and August 2018, and with hyperferritinemia of ≥500 µg/L were included. Patients with HLH were excluded. All patients were categorized into non-sepsis, sepsis, and septic shock. They were also classified into 17 disease groups, based on their ICD-10 codes, and pre-existing immunosuppression was determined. Uni- and multivariable linear regression analyses were performed in all patients. RESULTS: A total of 2583 patients were analyzed. Multivariable linear regression analysis revealed positive associations of maximum SOFA score, sepsis or septic shock, liver disease (except hepatitis), and hematological malignancy with maximum ferritin. T/NK cell lymphoma, acute myeloblastic leukemia, Kaposi's sarcoma, acute or subacute liver failure, and hepatic veno-occlusive disease were positively associated with maximum ferritin in post-hoc multivariable linear regression analysis. CONCLUSIONS: Sepsis or septic shock, liver disease (except hepatitis) and hematological malignancy are important differential diagnoses in hyperferritinemic adult critically ill patients without HLH. Together with HLH, they complete the quartet of important differential diagnoses of hyperferritinemia in adult critically ill patients. As these conditions are also related to HLH, it is important to apply HLH-2004 criteria for exclusion of HLH in hyperferritinemic patients. Hyperferritinemic critically ill patients without HLH require quick investigation of differential diagnoses.

Bimanual Grasping Adheres to Weber's Law.

Weber's law states that our ability to detect changes in stimulus attributes decreases linearly with their magnitude. This principle holds true for many attributes across sensory modalities but appears to be violated in grasping. One explanation for the failure to observe Weber's law in grasping is that its effect is masked by biomechanical constraints of the hand. We tested this hypothesis using a bimanual task that eliminates biomechanical constraints. Participants either grasped differently sized boxes that were comfortably within their arm span (action task) or estimated their width (perceptual task). Within each task, there were two conditions: One where the hands' start positions remained fixed for all object sizes (meaning the distance between the initial and final hand-positions varied with object size), and one in which the hands' start positions adapted with object size (such that the distance between the initial and final hand-position remained constant). We observed adherence to Weber's law in bimanual estimation and grasping across both conditions. Our results conflict with a previous study that reported the absence of Weber's law in bimanual grasping. We discuss potential explanations for these divergent findings and encourage further research on whether Weber's law persists when biomechanical constraints are reduced.

Mindfulness training during brief periods of hospitalization in multiple sclerosis (MS): beneficial alterations in fatigue and the mediating role of depression.

OBJECTIVES: Persons with MS (PwMS) are frequently affected by fatigue and depression. Mindfulness-based interventions may reduce these symptoms in PwMS and consequently their application has been extended to various settings. Only few efforts have been made to explore effects of short-term mindfulness training during brief periods of hospitalization. In the current study, the feasibility and potential effects of short-term mindfulness training on depression, fatigue, rumination and cognition were explored in PwMS in an acute-care hospital setting. Based on previous work, it was further examined whether the relation between trait mindfulness and fatigue prior to and following the intervention was mediated by depression and whether a mediation effect was also observable throughout the intervention. METHODS: A short-term mindfulness training protocol was developed, tailored to the requirements of the acute-care setting. Subsequently, 30 PwMS were recruited sequentially and received mindfulness training during the routine clinical process (median duration in hospital: eight days, number of sessions: four). Participants completed relevant self-report measures (depression, fatigue, rumination) and a neuropsychological assessment before and after training. RESULTS: Participants reported significantly increased trait mindfulness and decreased depression and fatigue following the intervention. Respective change scores were highly correlated so that increased trait mindfulness was associated with decreased symptoms. In the rumination domain, patients reported a tendency for an increased adaptive ability to engage in distractive behavior during arising negative mood. Other measures of trait rumination and cognition remained relatively stable. Results of the mediation analyses indicated that depression mediated the negative relationship between trait mindfulness and fatigue symptoms at pre and post assessments. With regards to the change scores, an association between mindfulness and cognitive fatigue ceased to be significant when depression was controlled, albeit in this case, the mediation effect did not reach significance. CONCLUSION: Results of the current study indicate that short-term mindfulness training during brief periods of hospitalization may be beneficial for PwMS. They further complement previous work by identifying depression as a potential mediator of the antagonistic relationship between mindfulness and fatigue. Based on the current exploratory study, future trials are warranted to address this mechanism of mindfulness training in more detail.

A Multisensory Deficit in the Perception of Pleasantness in Parkinson's Disease.

BACKGROUND: There is growing interest in non-motor symptoms in Parkinson's disease (PD), due to the impact on quality of life. Anhedonia, the inability to experience joy and lust, has a prevalence of up to 46% in PD. The perception of pleasantness of an odor is reduced in anhedonia without PD. We previously showed a reduced hedonic olfactory perception in PD, i.e., patients evaluated odors as less pleasant or unpleasant compared to controls. This deficit correlated with anhedonia. OBJECTIVE: We aimed to confirm these findings. Moreover, we hypothesized that the perception of pleasantness in PD is affected on a multisensory level and correlates with anhedonia. Therefore, we assessed olfactory, visual and acoustic evaluation of pleasantness in PD and healthy individuals. METHODS: Participants had to rate the pleasantness of 22 odors, pictures, and sounds on a nine-point Likert scale. Depression, anhedonia, and apathy were assessed by means of questionnaires. Results of the pleasantness-rating were compared between groups and correlated to scores of the questionnaires. RESULTS: In particular pleasant and unpleasant stimuli across all three modalities are perceived less intense in PD, suggesting that a reduced range of perception of pleasantness is a multisensory phenomenon. However, only a reduction of visual hedonic perception correlated with anhedonia in PD. A correlation of reduced perception of pleasantness with apathy or depression was not present. CONCLUSION: We provide evidence for a multisensory deficit in the perception of pleasantness. Further studies should delineate the underlying neural circuity and the diagnostic value to detect neuropsychiatric symptoms in PD.