Impact of parental body mass index at diagnosis on obesity in survivors of pediatric craniopharyngioma.

OBJECTIVE: It is well known that both genetic background and lifestyle influence the development of "general" obesity. However, the role of parental body mass index (BMI) on the development of obesity in long-term survivors of childhood-onset craniopharyngioma (CP) is not well understood. This study analyzed the correlation of patients' BMI at diagnosis and last visit and parental BMI at CP diagnosis and further explored potential risk factors for obesity in CP patients. DESIGN: Registry-based retrospective cohort study. METHODS: 291 CP patients and their parents recruited in the German KRANIOPHARYNGEOM studies were included. Correlations between patient's BMI SDS at CP diagnosis and last visit and parental BMI at CP diagnosis were analyzed. The associations between hypothalamic damage, maternal/paternal BMI and CP patients' obesity at last visit were analyzed by multivariable logistic regression. RESULTS: At follow-up, 52% of CP patients developed obesity (BMI>3SDS). Patient's BMI SDS at last visit was moderately correlated with BMI-SDS at CP diagnosis (r=0.48, 95%-CI 0.38-0.58, p<0.001), and also with maternal BMI at diagnosis (r=0.28, 95%-CI 0.17-0.38, p<0.001) and paternal BMI at diagnosis (r=0.3, 95% CI-0.19-0.41, p<0.001). However, the contributing role of parental BMI to the pathogenesis of obesity was small compared to the impact of hypothalamic damage. CONCLUSIONS: We conclude that besides hypothalamic damage, parental disposition for obesity is associated with the development of obesity in patients after CP. Our results indicate that also the family situation could have an influence on the development of obesity after CP and might be a therapeutic target.

Sensorimotor prediction is used to direct gaze toward task-relevant locations in a goal-directed throwing task.

Previous research has shown that action effects of self-generated movements are internally predicted before outcome feedback becomes available. To test whether these sensorimotor predictions are used to facilitate visual information uptake for feedback processing, we measured eye movements during the execution of a goal-directed throwing task. Participants could fully observe the effects of their throwing actions (ball trajectory, and either hitting or missing a target) in most of the trials. In a portion of the trials, the ball trajectory was not visible, and participants only received static information about the outcome. We observed a large proportion of predictive saccades, shifting gaze toward the goal region before the ball arrived and outcome feedback became available. Fixation locations after predictive saccades systematically covaried with future ball positions in trials with continuous ball flight information, but notably also in trials with static outcome feedback and only efferent and proprioceptive information about the movement that could be used for predictions. Fixation durations at the chosen positions after feedback onset were modulated by action outcome (longer durations for misses than for hits) and outcome uncertainty (longer durations for narrow vs. clear outcomes). Combining both effects, durations were longest for narrow errors and shortest for clear hits, indicating that the chosen locations offer informational value for feedback processing. Thus, humans are able to use sensorimotor predictions to direct their gaze toward task-relevant feedback locations. Outcome-dependent saccade latency differences (miss vs. hit) indicate that also predictive valuation processes are involved in planning predictive saccades.

When experience with scenes foils attentional orienting: ERP evidence against flexible target-context mapping in visual search.

Visual search is speeded when a target is repeatedly presented in an invariant scene context of nontargets (contextual cueing), demonstrating observers' capability for using statistical long-term memory (LTM) to make predictions about upcoming sensory events, thus improving attentional orienting. In the current study, we investigated whether expectations arising from individual, learned environmental structures can encompass multiple target locations. We recorded event-related potentials (ERPs) while participants performed a contextual cueing search task with repeated and non-repeated spatial item configurations. Notably, a given search display could be associated with either a single target location (standard contextual cueing) or two possible target locations. Our result showed that LTM-guided attention was always limited to only one target position in single- but also in the dual-target displays, as evidenced by expedited reaction times (RTs) and enhanced N1pc and N2pc deflections contralateral to one ("dominant") target of up to two repeating target locations. This contrasts with the processing of non-learned ("minor") target positions (in dual-target displays), which revealed slowed RTs alongside an initial N1pc "misguidance" signal that then vanished in the subsequent N2pc. This RT slowing was accompanied by enhanced N200 and N400 waveforms over fronto-central electrodes, suggesting that control mechanisms regulate the competition between dominant and minor targets. Our study thus reveals a dissociation in processing dominant versus minor targets: While LTM templates guide attention to dominant targets, minor targets necessitate control processes to overcome the automatic bias towards previously learned, dominant target locations.

Contextual facilitation: Separable roles of contextual guidance and context suppression in visual search.

Visual search is facilitated when targets are repeatedly encountered at a fixed position relative to an invariant distractor layout, compared to random distractor arrangements. However, standard investigations of this contextual-facilitation effect employ fixed distractor layouts that predict a constant target location, which does not always reflect real-world situations where the target location may vary relative to an invariant distractor arrangement. To explore the mechanisms involved in contextual learning, we employed a training-test procedure, introducing not only the standard full-repeated displays with fixed target-distractor locations but also distractor-repeated displays in which the distractor arrangement remained unchanged but the target locations varied. During the training phase, participants encountered three types of display: full-repeated, distractor-repeated, and random arrangements. The results revealed full-repeated displays to engender larger performance gains than distractor-repeated displays, relative to the random-display baseline. In the test phase, the gains were substantially reduced when full-repeated displays changed into distractor-repeated displays, while the transition from distractor-repeated to full-repeated displays failed to yield additional gains. We take this pattern to indicate that contextual learning can improve performance with both predictive and non-predictive (repeated) contexts, employing distinct mechanisms: contextual guidance and context suppression, respectively. We consider how these mechanisms might be implemented (neuro-)computationally.

Outcome After Modern Proton Beam Therapy in Childhood Craniopharyngioma: Results of the Prospective Registry Study KiProReg.

PURPOSE: Craniopharyngiomas (CPs) are rare tumors of the sellar region often leading to significant comorbidities due to their close proximity to critical structures. The aim of this study was to analyze survival outcome and late toxicities after surgery and proton beam therapy (PBT) in childhood CPs. METHODS AND MATERIALS: Within the prospective registry study "KiProReg" (DRKS0000536), data of 74 childhood patients with CP, receiving PBT between August 2013 to June 2022 were eligible. Late toxicities were analyzed according to the grading system of the Common Terminology Criteria for Adverse Events, version 4.0. RESULTS: Median follow-up since first diagnosis was 4.3 years (range, 0.8-14.7). In addition, 75.7% of patients received PBT at time of disease progression or recurrence, whereas 24.3% as part of their primary therapy (definitive or adjuvant). Predominantly (85.1%), pencil beam scanning technique was used. The median total dose and initial tumor volume were 5400 cGy relative biologic effectiveness (RBE) and 17.64 cm³ (range, 3.07-300.59), respectively. The estimated (±SE) 3-year overall survival, progression-free, and cystic failure-free survival rate after PBT were 98.2% (±1.7), 94.7% (±3.0), and 76.8% (±5.4), respectively. All local failures (n = 3) were in-field relapses necessitating intervention and occurred exclusively in patients receiving PBT at progression or recurrence. Early cystic enlargements after PBT were typically asymptomatic and self-limiting. Fatigue, headaches, vision disorders, obesity, and endocrinopathies were the predominant late toxicities. No high-grade (≥3) new-onset visual impairment or cognitive deterioration occurred compared with baseline. The presence of cognitive impairments at the end of follow-up correlated with size of the planning target volume (P = .034), Dmean dose to the temporal lobes (P = .032, P = .045) and the number of surgical interventions before PBT (P = .029). CONCLUSIONS: Our findings demonstrate favorable local control rates using modern PBT with acceptable late toxicities. Cyst growth within 12 months after radiation therapy is typically not associated with tumor progression. Longer follow-up must be awaited to confirm results.

ERPs and alpha oscillations track the encoding and maintenance of object-based representations in visual working memory.

When memorizing an integrated object such as a Kanizsa figure, the completion of parts into a coherent whole is attained by grouping processes which render a whole-object representation in visual working memory (VWM). The present study measured event-related potentials (ERPs) and oscillatory amplitudes to track these processes of encoding and representing multiple features of an object in VWM. To this end, a change detection task was performed, which required observers to memorize both the orientations and colors of six "pacman" items while inducing configurations of the pacmen that systematically varied in terms of their grouping strength. The results revealed an effect of object configuration in VWM despite physically constant visual input: change detection for both orientation and color features was more accurate with increased grouping strength. At the electrophysiological level, the lateralized ERPs and alpha activity mirrored this behavioral pattern. Perception of the orientation features gave rise to the encoding of a grouped object as reflected by the amplitudes of the Ppc. The grouped object structure, in turn, modulated attention to both orientation and color features as indicated by the enhanced N1pc and N2pc. Finally, during item retention, the representation of individual objects and the concurrent allocation of attention to these memorized objects were modulated by grouping, as reflected by variations in the CDA amplitude and a concurrent lateralized alpha suppression, respectively. These results indicate that memorizing multiple features of grouped, to-be-integrated objects involves multiple, sequential stages of processing, providing support for a hierarchical model of object representations in VWM.

Vascular Morbidity and Mortality in Craniopharyngioma Patients-A Scoping Review.

Craniopharyngioma (CP) treatment, including surgery and radiotherapy, can have short- and long-term vascular side effects. Hypothalamic damage is related to morbid obesity and may increase the lifelong risk of experiencing vascular events in CP patients. This review summarized the available evidence regarding vascular complications in adamantinomatous or papillary CP patients, whatever their age at diagnosis. Three databases (Medline, CINAHL, Web of Science) were searched (06/2023) to retrieve eligible articles. The search was limited to peer-reviewed articles. Titles, abstracts, and full texts were screened by two independent reviewers, and data were extracted using a self-developed grid. Seventy-two studies were included in this review; the majority were case reports. Reported vascular sequela that occurred due to surgery were fusiform dilation of the carotid artery, stroke, vasospasm, hemorrhage, and aneurysm. Related conditions that emerged due to radiotherapy included Moyamoya syndrome and cavernoma. Cardiovascular morbidity and mortality often lead to hypothalamic obesity and metabolic syndrome in CP patients. Vascular damage is a rare complication of CP treatment. Surgical strategies should protect the surrounding hypothalamic and vascular structures. Patients receiving radiotherapy, particularly at a young age, should undergo magnetic resonance angiography monitoring to identify possible neurovascular sequela during post-treatment care.

Terms of debate: Consensus definitions to guide the scientific discourse on visual distraction.

Hypothesis-driven research rests on clearly articulated scientific theories. The building blocks for communicating these theories are scientific terms. Obviously, communication - and thus, scientific progress - is hampered if the meaning of these terms varies idiosyncratically across (sub)fields and even across individual researchers within the same subfield. We have formed an international group of experts representing various theoretical stances with the goal to homogenize the use of the terms that are most relevant to fundamental research on visual distraction in visual search. Our discussions revealed striking heterogeneity and we had to invest much time and effort to increase our mutual understanding of each other's use of central terms, which turned out to be strongly related to our respective theoretical positions. We present the outcomes of these discussions in a glossary and provide some context in several essays. Specifically, we explicate how central terms are used in the distraction literature and consensually sharpen their definitions in order to enable communication across theoretical standpoints. Where applicable, we also explain how the respective constructs can be measured. We believe that this novel type of adversarial collaboration can serve as a model for other fields of psychological research that strive to build a solid groundwork for theorizing and communicating by establishing a common language. For the field of visual distraction, the present paper should facilitate communication across theoretical standpoints and may serve as an introduction and reference text for newcomers.

Mission impossible? Spatial context relearning following a target relocation event depends on cue predictiveness.

Visual search for a target is faster when the spatial layout of distractors is repeatedly encountered, illustrating that statistical learning of contextual invariances facilitates attentional guidance (contextual cueing; Chun & Jiang, 1998, Cognitive Psychology, 36, 28-71). While contextual learning is usually relatively efficient, relocating the target to an unexpected location (within an otherwise unchanged search layout) typically abolishes contextual cueing and the benefits deriving from invariant contexts recover only slowly with extensive training (Zellin et al., 2014, Psychonomic Bulletin & Review, 21(4), 1073-1079). However, a recent study by Peterson et al. (2022, Attention, Perception, & Psychophysics, 84(2), 474-489) in fact reported rather strong adaptation of spatial contextual memories following target position changes, thus contrasting with prior work. Peterson et al. argued that previous studies may have been underpowered to detect a reliable recovery of contextual cueing after the change. However, their experiments also used a specific display design that frequently presented the targets at the same locations, which might reduce the predictability of the contextual cues thereby facilitating its flexible relearning (irrespective of statistical power). The current study was a (high-powered) replication of Peterson et al., taking into account both statistical power and target overlap in context-memory adaptation. We found reliable contextual cueing for the initial target location irrespective of whether the targets shared their location across multiple displays, or not. However, contextual adaptation following a target relocation event occurred only when target locations were shared. This suggests that cue predictability modulates contextual adaptation, over and above a possible (yet negligible) influence of statistical power.

Changes in attentional breadth scale with the demands of Kanizsa-figure object completion-evidence from pupillometry.

The present study investigated whether the integration of separate parts into a whole-object representation varies with the amount of available attentional resources. To this end, two experiments were performed, which required observers to maintain central fixation while searching in peripheral vision for a target among various distractor configurations. The target could either be a "grouped" whole-object Kanizsa figure, or an "ungrouped" configuration of identical figural parts, but which do not support object completion processes to the same extent. In the experiments, accuracies and changes in pupil size were assessed, with the latter reflecting a marker of the covert allocation of attention in the periphery. Experiment 1 revealed a performance benefit for grouped (relative to ungrouped) targets, which increased with decreasing distance from fixation. By contrast, search for ungrouped targets was comparably poor in accuracy without revealing any eccentricity-dependent variation. Moreover, measures of pupillary dilation mirrored this eccentricity-dependent advantage in localizing grouped targets. Next, in Experiment 2, an additional attention-demanding foveal task was introduced in order to further reduce the availability of attentional resources for the peripheral detection task. This additional task hampered performance overall, alongside with corresponding pupil size changes. However, there was still a substantial benefit for grouped over ungrouped targets in both the behavioral and the pupillometric data. This shows that perceptual grouping scales with the allocation of attention even when only residual attentional resources are available to trigger the representation of a complete (target) object, thus illustrating that object completion operates in the "near absence" of attention.

Environmental regularities mitigate attentional misguidance in contextual cueing of visual search.

Visual search is faster when a fixed target location is paired with a spatially invariant (vs. randomly changing) distractor configuration, thus indicating that repeated contexts are learned, thereby guiding attention to the target (contextual cueing [CC]). Evidence for memory-guided attention has also been revealed with electrophysiological (electroencephalographic [EEG]) recordings, starting with an enhanced early posterior negativity (N1pc), which signals a preattentive bias toward the target, and, subsequently, attentional and postselective components, such as the posterior contralateral negativity (PCN) and contralateral delay activity (CDA), respectively. Despite effective learning, relearning of previously acquired contexts is inflexible: The CC benefits disappear when the target is relocated to a new position within an otherwise invariant context and corresponding EEG correlates are diminished. The present study tested whether global statistical properties that induce predictions going beyond the immediate invariant layout can facilitate contextual relearning. Global statistical regularities were implemented by presenting repeated and nonrepeated displays in separate streaks (mini blocks) of trials in the relocation phase, with individual displays being presented in a fixed and thus predictable order. Our results revealed a significant CC effect (and an associated modulation of the N1pc, PCN, and CDA components) during initial learning. Critically, the global statistical regularities in the relocation phase also resulted in a reliable CC effect, thus revealing effective relearning with predictive streaks. Moreover, this relearning was reflected in an enhanced PCN amplitude for repeated relative to nonrepeated contexts. Temporally ordered contexts may thus adapt memory-based guidance of attention, particularly the allocation of covert attention in the visual display. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Task-irrelevant valence-preferred colors boost visual search for a singleton-shape target.

Some studies have suggested that emotion-associated features might influence attentional capture. However, demonstrating valence-dependent distractor interference has proven challenging, possibly due to the neglect of individuals' color-valence preferences in standard, averaged reaction-time (RT) measures. To address this, we investigated valence-driven attentional-capture using an association phase in which emotionally neutral vs. positive-feedback photographs were paired with two alternative target colors, red vs. green. This was followed by a test phase requiring participants to search for a pop-out shape target in the presence or absence of an emotion-associated color. In Experiments 1 and 2, this color could only appear in a distractor, while in Experiment 3, it appeared in the target. Analyzing the standard, averaged RT measures, we found no significant valence association or valence-modulated attentional capture. However, correlational analyses revealed a positive relationship between individual participants' color-valence preference during the association phase and their valence-based effect during the test phase. Moreover, most individuals favored red over green in the association phase, leading to marked color-related asymmetries in the average measures. Crucially, the presence of the valence-preferred color anywhere in the test display facilitated RTs. This effect persisted even when the color appeared in one of the distractors (Experiments 1 and 2), at variance with this distractor capturing attention. These findings suggest that task-irrelevant valence-preferred color signals were registered pre-attentively and boosted performance, likely by raising the general (non-spatial) alertness level. However, these signals were likely kept out of attentional-priority computation to prevent inadvertent attentional capture.

Outcome after proton beam therapy versus photon-based radiation therapy in childhood-onset craniopharyngioma patients-results of KRANIOPHARYNGEOM 2007.

Background: Proton beam therapy (PBT) is being increas16ingly used to treat residual craniopharyngioma (CP) after hypothalamus-sparing surgery. Compared to photon-based radiation therapy (XRT) with PBT, less irradiation in the penumbra reduces the scattered dose to critical organs neighboring but outside the area of treatment, minimizing the risk of sequelae. Patients and methods: Between 2007 and 2019, 99 of 290 (34%) childhood-onset CP patients recruited in KRANIOPHARYNGEOM 2007 received external radiation therapy (RT) (65% PBT, 35% XRT). Outcome was analyzed in terms of survival, endocrinological and anthropometric parameters (BMI and height SDS), quality of life (QoL using PEDQOL), and functional capacity (FMH) with special regard to irradiation technique. Results: PBT became predominant (used in 43% and 72% of all irradiated patients registered within the first and second halves of the recruitment period, between 2008 and 2013 and 2013 and 2018, respectively). Five-year event-free survival rates after PBT or XRT were comparable (92% ± 4% vs. 91% ± 4%, p = 0.42) and higher than for the whole cohort since diagnosis, including non-RT patients (37% ± 4%). Radiation doses to the hypothalamus and pituitary did not differ between PBT and XRT. Endocrine deficits due to disturbances of the hypothalamic-pituitary axis (HPA) were already common before irradiation. During the first 5 years after CP diagnosis/RT, no differences between PBT, XRT, and non-RT CP patients concerning functional capacity and anthropometric parameters have been obtained. Only for the PEDQOL domain "physical function", parental-assessed QoL was lower 12 months after PBT versus XRT or non-RT patients. Conclusion: QoL, functional capacity, degree of obesity, and endocrinopathy varied over time from diagnosis, but by 5 years, there was no significant difference between PBT and XRT upfront or delayed, nor was there any compromise in historic survival rates, which remained high >90%. RT of any type is extremely effective at stabilizing disease after hypothalamic-sparing surgery. The purported specific benefits of PBT-reducing sequelae are not proven in this study where the organ of critical interest is itself diseased, increasing an urgent need to better address and treat the tumor-induced endocrine harm from diagnosis in dedicated pituitary services. Other hypothesized benefits of PBT versus XRT on vascular events and secondary cancers await longer comparison. Clinical trial registration number: https://clinicaltrials.gov/study/, identifier NCT01272622.

Vision-related quality of life in patients with childhood-onset craniopharyngioma.

Quality of life (QoL) is a critical component of aftercare in survivors of childhood-onset craniopharyngioma (CP). Visual impairment adversely affects QoL after CP. This study assessed the frequency of visual impairment in patients with CP and its association with QoL. This study analyzed vision-related QoL in patients recruited 2000-2019 in the prospective cohort studies KRANIOPHARYNGEOM 2000/2007. Ophthalmologic examinations were performed at diagnosis, three, 12, and 36 months, respectively after the diagnosis. The QoL (PEDQOL) scores, were also evaluated at three, 12, and 36 months, respectively after the CP diagnosis. Multivariable logistic regression was used to analyze factors associated with visual impairment during follow-up. One-hundred twenty patients were included in this study. On ophthalmological examination, visual impairment was observed in the majority of the patients (n = 84, 70%) at CP diagnosis. After surgery, vision was restored in 27 patients (32%) with visual impairment at diagnosis. In the first (p = 0.017) and third (p = 0.011) year after diagnosis, parents of patients with visual impairment reported lower social functioning (family). Reduced autonomy was found three years after diagnosis in self- (p = 0.029) and parental (p = 0.048) assessments. Next to visual impairment at diagnosis, no additional risk factors for visual impairment during follow-up could be identified. Visual impairment has a clinically relevant impact on QoL after CP. The visual status at CP diagnosis determines the visual outcome during follow-up. Early detection of visual impairment, regular QoL assessments, and risk-appropriate aftercare are recommended.Clinical Trial Registration KRANIOPHARYNGEOM 2000 (Clinical trial registration number: NCT00258453) and KRANIOPHARYNGEOM 2007 (Clinical trial registration number: NCT01272622).

Perinatally diagnosed congenital craniopharyngiomas in the KRANIOPHARYNGEOM trials.

Background: Craniopharyngiomas (CPs) are rare embryonic tumors. Clinical presentation and outcome of patients perinatally diagnosed with congenital CP (cCP) are not clear and refer mainly to a few case reports in the literature. The aim of this study was to analyze clinical presentation and outcome in patients with cCP. Study design: Three hundred and sixty-one patients diagnosed with adamantinomatous CP were recruited 2007-2022 in KRANIOPHARYNGEOM 2007/Registry 2019 and prospectively observed. In two cases, cCP was diagnosed prenatally and in one case on the second day of life. Pre- and perinatal diagnostic findings, postnatal evaluation, and therapeutic interventions and outcome in these three cases of cCP were analyzed. Results: All patients survived. One patient developed psychomotor retardation and a mild hemiparesis. Prenatal routine ultrasound examination led to the diagnosis of cCP. Tumor resection was performed during the early postnatal period (range: 11-51 days of age). Functional capacity, measured by Fertigkeitenskala-Münster-Heidelberg (FMH) was reduced in three and behavioral parameters, measured by the Strength and Difficulties Questionnaire (SDQ) were abnormal in two cases. Conclusion: cCP is a rare diagnosis with a prevalence of 0.83% in our study group. Compared to cases reported in the literature, the presented cases were treated immediately and had a better prognosis. Based on improvements of diagnostic and therapeutic techniques, prenatal diagnosis of cCP should lead to transfer prior to delivery of cCP patients to a specialized center for delivery and postnatal treatment of newborns with sellar masses by a multidisciplinary team to secure the improved prognosis of these patients. Significance statement: We previously reported that lower event-free survival rates after craniopharyngioma are associated with younger age at diagnosis. Perinatally diagnosed congenital craniopharyngiomas are very rare. This article presents three unique cases with congenital craniopharyngioma, comparing their diagnostics, therapy, and development. All three cases had surgery during the early postnatal period with sparing of the posterior hypothalamus. In each case, endocrinopathy was present at follow-up. Low functional capacity was reported in all cases and an abnormal total difficulties score in two cases. Compared to the literature, the presented cases had better prognosis in morbidity and mortality. This report and the review of the literature confirm the importance of a multidisciplinary approach in the diagnostic and treatment of the very rare condition of congenital craniopharyngioma.

Learning-Induced Plasticity Enhances the Capacity of Visual Working Memory.

Visual working memory (VWM) is limited in capacity, though memorizing meaningful objects may refine this limitation. However, meaningful and meaningless stimuli typically differ perceptually, and objects' associations with meaning are usually already established outside the laboratory, potentially confounding experimental findings. Here, in two experiments with young adults (N = 45 and N = 20), we controlled for these influences by having observers actively learn associations of (for them) initially meaningless stimuli: Chinese characters, half of which were consistently paired with pictures of animals or everyday objects in a learning phase. This phase was preceded and followed by a (pre- and postlearning) change-detection task to assess VWM performance. The results revealed that short-term retention was enhanced after learning, particularly for meaning-associated characters, although participants did not quite reach the accuracy level attained by native Chinese observers (young adults, N = 20). These results thus provide direct experimental evidence that participants' VWM of objects is boosted by them having acquired a long-term-memory association with meaning.