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Compression, the ability to recode information in a denser format, is a core property of working memory (WM). Previous studies have shown that the ability to compress information largely benefits WM performance. Importantly, recent evidence also suggests compression as freeing up WM resources, thus enhancing recall performance for other, less compressible information. Contrary to the traditional view positing that between-item similarity decreases WM performance, this study shows that between-item similarity can be used to free up WM resources through compression. Across a series of four experiments, we show that between-item similarity not only enhances recall performance for similar items themselves, but also for other, less compressible items within the same list, and this in the semantic (Experiment 1), phonological (Experiment 2), visuospatial (Experiment 3), and visual (Experiment 4) domains. Across these different domains, a consistent pattern of results emerged: between-item similarity proactively-but not retroactively-enhanced WM performance for other items, and this as compared with a condition in which between-item similarity at the whole-list level was minimized. We propose that between-item similarity in any domain may impact WM using the same underlying machinery: via a compression mechanism, which allows an efficient reallocation of WM resources. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

A central tenet of the adaptive-memory framework is that memory has not merely evolved to help us relive the past but to prepare us for the future. In reciprocal social exchange, for instance, people must learn from previous experiences to approach cooperators and to avoid cheaters. In this sense, adaptive memory is inherently prospective. The present research is the first to test this central assumption of the adaptive-memory framework. In Experiments 1 and 2, participants played a Prisoner's Dilemma game and encountered cheating, cooperating, and neutral partners. The faces of these partners later reappeared during an event-based prospective-memory task. Participants showed better prospective-memory performance for cooperator and cheater faces than for neutral control faces. Multinomial processing-tree modeling served to separate the prospective component (remembering that an action needs to be performed) from the retrospective component (recognizing the target faces) of prospective memory. Superior prospective-memory performance for cooperator and cheater faces was attributable to a stronger prospective component, whereas the retrospective component remained unaffected. Experiment 3 showed that emotional descriptions of targets were ineffective in increasing prospective memory, suggesting that emotional valence alone cannot account for the prospective-memory advantage found in Experiments 1 and 2. The results suggest that cooperating with someone or being cheated by someone has a strong impact on future-oriented cognition. Enhanced prospective memory for cooperator and cheater faces may have an important function for maintaining reciprocal relationships and for avoiding cheaters. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Previous research assumes that executive functions such as inhibition, shifting and updating explain individual differences in cognitive abilities. Of these three executive functions, updating was previously found to relate most strongly to fluid intelligence. However, this relationship could be a methodological artifact: Measures of inhibition and shifting usually isolate the contribution of this executive function to performance by contrasting conditions with high and low demands on these processes, whereas updating is measured by overall accuracy in working memory tasks involving updating. This updating measure conflates updating-specific individual differences (e.g., removal of outdated information) with variance in working memory maintenance. Re-analyzing data (N = 111) from von Bastian et al. (2016), we separated updating-specific variance from working memory maintenance variance. Updating contributed only 15% to individual differences in performance in the updating tasks, and it correlated neither with fluid intelligence nor with independent working memory measures reflecting storage and processing or relational integration. In contrast, the working memory maintenance component of the updating task correlated with both abilities. These findings challenge the view that updating contributes to variance in higher cognitive abilities.

Introduction: Fast and minimally invasive approaches for early diagnosis of Alzheimer's disease (AD) are highly anticipated. Evidence of adaptive immune cells responding to cerebral β-amyloidosis has raised the question of whether immune markers could be used as proxies for β-amyloid accumulation in the brain. Methods: Here, we apply multidimensional mass-cytometry combined with unbiased machine-learning techniques to immunophenotype peripheral blood mononuclear cells from a total of 251 participants in cross-sectional and longitudinal studies. Results: We show that increases in antigen-experienced adaptive immune cells in the blood, particularly CD45RA-reactivated T effector memory (TEMRA) cells, are associated with early accumulation of brain β-amyloid and with changes in plasma AD biomarkers in still cognitively healthy subjects. Discussion: Our results suggest that preclinical AD pathology is linked to systemic alterations of the adaptive immune system. These immunophenotype changes may help identify and develop novel diagnostic tools for early AD assessment and better understand clinical outcomes., Alzheimer's & Dementia: The Journal of the Alzheimer's Association, ISSN:1552-5279, ISSN:1552-5260

Introduction: The treatment of hydrocephalus has been a topic of intense research ever since the first clinically successful use of a valved cerebrospinal fluid shunt 72 years ago. While ample studies elucidating different phenomena impacting this treatment exist, there are still gaps to be filled. Specifically, how intracranial, intrathecal, arterial, and venous pressures react and communicate with each other simultaneously. Methods: An in-vivo sheep trial (n = 6) was conducted to evaluate and quantify the communication existing within the cranio-spinal, arterial, and venous systems (1 kHz sampling frequency). Standardized intrathecal infusion testing was performed using an automated infusion apparatus, including bolus and constant pressure infusions. Bolus infusions entailed six lumbar intrathecal infusions of 2 mL Ringer’s solution. Constant pressure infusions were comprised of six regulated pressure steps of 3.75 mmHg for periods of 7 min each. Mean pressure reactions, pulse amplitude reactions, and outflow resistance were calculated. Results: All sheep showed intracranial pressure reactions to acute increases of intrathecal pressure, with four of six sheep showing clear cranio-spinal communication. During bolus infusions, the increases of mean pressure for intrathecal, intracranial, arterial, and venous pressure were 16.6 ± 0.9, 15.4 ± 0.8, 3.9 ± 0.8, and 0.1 ± 0.2 mmHg with corresponding pulse amplitude increases of 2.4 ± 0.3, 1.3 ± 0.3, 1.3 ± 0.3, and 0.2 ± 0.1 mmHg, respectively. During constant pressure infusions, mean increases from baseline were 14.6 ± 3.8, 15.5 ± 4.2, 4.2 ± 8.2, and 3.2 ± 2.4 mmHg with the corresponding pulse amplitude increases of 2.5 ± 3.6, 2.5 ± 3.0, 7.7 ± 4.3, and 0.7 ± 2.0 mmHg for intrathecal, intracranial, arterial, and venous pulse amplitude, respectively. Outflow resistances were calculated as 51.6 ± 7.8 and 77.8 ± 14.5 mmHg/mL/min for the bolus and constant pressure infusion methods, respectively—showing deviations between the two estimation methods. Conclusions: Standardized infusion tests with multi-compartmental pressure recordings in sheep have helped capture distinct reactions between the intrathecal, intracranial, arterial, and venous systems. Volumetric pressure changes in the intrathecal space have been shown to propagate to the intraventricular and arterial systems in our sample,and to the venous side in individual cases. These results represent an important step into achieving a more complete quantitative understanding of how an acute rise in intrathecal pressure can propagate and influence other systems., Fluids and Barriers of the CNS, 19 (1), ISSN:2045-8118

Sequential decision making-making a decision where available options are encountered successively-is a hallmark of everyday life. Such decisions require deciding to accept or reject an alternative without knowing potential future options. Prior work focused on understanding choice behavior by developing decision models that capture human choices in such tasks. We investigated people's adaptive behavior in changing environments in light of their cognitive strategies. We present two studies in which we modified (a) outcome variance and (b) the time horizon and provide empirical evidence that people adapt to both context manipulations. Furthermore, we apply a recently developed threshold model of optimal stopping to our data to disentangle different cognitive processes involved in optimal stopping behavior. The results from Study 1 show that participants adaptively scaled the values of the sampling distribution to its variance, suggesting that the value of an option is perceived in relative rather than absolute terms. The results from Study 2 suggest that increasing the time horizon decreases the initial acceptance level, but less strongly than would be optimal. Furthermore, for longer sequences, participants more weakly adjusted this acceptance threshold over time than for shorter sequences. Further correlations between individual estimates in each condition indicate that individual differences between the participants' thresholds remain fairly stable between the conditions, pointing toward an additive effect of our manipulations. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

The capacity limitations of visual working memory may be bypassed by verbal labeling. In adults, labeling increases estimates of both quantity and quality of visual working memory. However, we do not know when children begin to use labeling and whether labeling similarly benefits visual memories of children under and over age 7. We assessed whether children benefit from prompted and spontaneous labeling opportunities, examining how labeling affects the storage of categorical (prototypical) and continuous (fine-grained) color information. Participants memorized colored candies for a continuous reproduction test either while remaining silent, labeling the colors aloud, or saying irrelevant syllables (discouraging verbal labeling). Mixture modeling confirmed that both categorical and continuous representations increased with age. Our labeling manipulation showed that spontaneous labeling increased with age. For the youngest children, prompted labeling especially boosted categorical memory, whereas labeling benefited categorical and continuous memory similarly in the older age groups. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Although phenobarbital (PB) is commonly used as a first-line antiseizure medication (ASM) for neonatal seizures, in 2015 we chose to replace it with levetiracetam (LEV), a third-generation ASM. Here, we compared the safety and efficacy of LEV and PB as first-line ASM, considering the years before and after modifying our treatment protocol.We conducted a retrospective cohort study of 108 neonates with electroencephalography (EEG)-confirmed seizures treated with first-line LEV or PB in 2012 to 2020.First-line ASM was LEV in 33 (31%) and PB in 75 (69%) neonates. The etiology included acute symptomatic seizures in 69% of cases (30% hypoxic-ischemic encephalopathy, 32% structural vascular, 6% infectious, otherwise metabolic) and neonatal epilepsy in 22% (5% structural due to brain malformation, 17% genetic). Forty-two of 108 (39%) neonates reached seizure freedom following first-line therapy. Treatment response did not vary by first-line ASM among all neonates, those with acute symptomatic seizures, or those with neonatal-onset epilepsy. Treatment response was lowest for neonates with a higher seizure frequency, particularly for those with status epilepticus versus rare seizures (P 0.001), irrespective of gestational age, etiology, or EEG findings. Adverse events were noted in 22 neonates treated with PB and in only one treated with LEV (P 0.001).Our study suggests a potential noninferiority and a more acceptable safety profile for LEV, which may thus be a reasonable option as first-line ASM for neonatal seizures in place of PB. Treatment should be initiated as early as possible since higher seizure frequencies predispose to less favorable responses.

How do verbal descriptions affect visual memory over the short and long term? Here we show for the first time that verbal labeling can boost visual memories, but the source of this benefit depends on whether representations are maintained over the short term in visual working memory or over the long term in visual long-term memory. Across three experiments, we contrasted color memory of randomly colored objects when participants labeled (a) the color, (b) the object, or (c) the color-object binding, to memory under an articulatory suppression condition inhibiting labeling. Memory was tested at two time points: after three objects (visual working memory) and at the end of the experiment (visual long-term memory). In Experiment 1, color labeling improved, whereas object labeling impaired, visual working memory in comparison to suppression. Visual long-term memory remained unchanged across conditions. Experiment 2 tested whether this was attributable to poor overall long-term learning by repeating the colored objects over three successive working memory trials. This increased performance over the short and long term, yet labeling did not change learning rate over repetitions or delayed memory performance, showing no long-term memory benefit. In Experiment 3, a labeling benefit was observed when the color-object binding was labeled both over the short and long term. Mixture modeling indicated that color-labeling benefits in visual working memory resulted from an increase of detailed visual memory, whereas long-term memory benefits accrued from categorical representations. Our findings point to dissociations on the role of language in visual working memory and visual long-term memory. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

The high metabolic demands of the brain require an efficient vascular system to be coupled with neural activity to supply adequate nutrients and oxygen. This supply is coordinated by the action of neurons, glial and vascular cells, known collectively as the neurovascular unit, which temporally and spatially regulate local cerebral blood flow through a process known as neurovascular coupling. In many neurodegenerative diseases, changes in functions of the neurovascular unit not only impair neurovascular coupling but also permeability of the blood-brain barrier, cerebral blood flow and clearance of waste from the brain. In order to study disease mechanisms, we need improved physiologically-relevant human models of the neurovascular unit. Advances towards modeling the cellular complexity of the neurovascular unit in vitro have been made using stem-cell derived organoids and more recently, vascularized organoids, enabling intricate studies of non-cell autonomous processes. Engineering and design innovations in microfluidic devices and tissue engineering are progressing our ability to interrogate the cerebrovasculature. These advanced models are being used to gain a better understanding of neurodegenerative disease processes and potential therapeutics. Continued innovation is required to build more physiologically-relevant models of the neurovascular unit encompassing both the cellular complexity and designed features to interrogate neurovascular unit functionality.

Both absolute and relative brain sizes vary greatly among and within the major vertebrate lineages. Scientists have long debated how larger brains in primates and hominins translate into greater cognitive performance, and in particular how to control for the relationship between the noncognitive functions of the brain and body size. One solution to this problem is to establish the slope of cognitive equivalence, i.e., the line connecting organisms with an identical bauplan but different body sizes. The original approach to estimate this slope through intraspecific regressions was abandoned after it became clear that it generated slopes that were too low by an unknown margin due to estimation error. Here, we revisit this method. We control for the error problem by focusing on highly dimorphic primate species with large sample sizes and fitting a line through the mean values for adult females and males. We obtain the best estimate for the slope of circa 0.27, a value much lower than those constructed using all mammal species and close to the value expected based on the genetic correlation between brain size and body size. We also find that the estimate of cognitive brain size based on cognitive equivalence fits empirical cognitive studies better than the encephalization quotient, which should therefore be avoided in future studies on primates and presumably mammals and birds in general. The use of residuals from the line of cognitive equivalence may change conclusions concerning the cognitive abilities of extant and extinct primate species, including hominins.

Several previous studies reported relationships between speed of information processing as measured with the drift parameter of the diffusion model (Ratcliff, 1978) and general intelligence. Most of these studies utilized only few tasks and none of them used more complex tasks. In contrast, our study (N = 125) was based on a large battery of 18 different response time tasks that varied both in content (numeric, figural, and verbal) and complexity (fast tasks with mean RTs of ca. 600 ms vs. more complex tasks with mean RTs of ca. 3,000 ms). Structural equation models indicated a strong relationship between a domain-general drift factor and general intelligence. Beyond that, domain-specific speed of information processing factors were closely related to the respective domain scores of the intelligence test. Furthermore, speed of information processing in the more complex tasks explained additional variance in general intelligence. In addition to these theoretically relevant findings, our study also makes methodological contributions showing that there are meaningful interindividual differences in content specific drift rates and that not only fast tasks, but also more complex tasks can be modeled with the diffusion model. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

To preoperatively assess the neurodevelopment of a predominantly white population of children with moyamoya angiopathy (MMA).Assessments of 40 children with MMA (24 females, 16 males; mean age 6y 11mo, range 20mo-16y) included tests for non-verbal IQ and fine motor skills, and questionnaires on quality of life, behaviour, and executive functions. The Paediatric Stroke Outcome Measure (PSOM) score was evaluated by a paediatric neurologist.Children with MMA had significantly lower non-verbal IQ scores (mean IQ 92.1, SD 19.6, p=0.015) and fine motor skills (z-score -1.84, p=0.004) than population norms. Patients with posterior cerebral artery (PCA) involvement had poorer non-verbal IQ scores than those without (79.6, SD 24.6 vs 95.2, SD 17.2, p=0.042). Higher PSOM scores were related to lower non-verbal IQ scores (Spearman's rank correlation coefficient -0.43, p=0.006), while the presence of stroke, bilaterality, disease versus syndrome, and age at diagnosis had no significant effect on non-verbal IQ. Quality of life, behaviour, and executive functions were in the typically developing range.Children with MMA are more likely to manifest intellectual and fine motor skill impairment before surgical intervention. PCA involvement is an additional risk factor for lower non-verbal IQ.Children with moyamoya angiopathy have intellectual and fine motor skill impairment before surgical intervention. Posterior cerebral artery involvement and higher Paediatric Stroke Outcome Measure scores may predict poorer performance.

AIM To determine predictors of full-scale IQ (FSIQ) in an international pediatric opsoclonus myoclonus syndrome (OMS) cohort. METHOD In this retrospective and prospective cohort study at three academic medical centers (2006-2013), the primary outcome measure, FSIQ, was categorized based on z-score: above average (≥+1), average (+1 to -1), mildly impaired (-1 to -2), and impaired (

Working memory (short WM) is the system responsible for holding mental representations temporarily available for later use in thought or action (Oberauer et al., 2018). Because WM has a severely limited capacity, WM content needs to be constantly updated to focus on current, relevant information. To enable seamless updating, there should be a mechanism that removes outdated information from WM. Recent studies show that under some conditions irrelevant content can be removed from WM with remarkable efficiency (e.g., Oberauer, 2018; Williams & Woodman, 2012): Oberauer (2018) had participants learn a set of six words (set-size 6 baseline) or three words (set-size 3 baseline) for a subsequent recognition test. In the recognition test, one of the previously studied words was presented in a randomly selected frame. The word could either match the word originally presented in that frame (50% of all trials) or not (mismatch, 50% of all trials). In a third condition (set size 6-3), six words were presented, but a random subset of three words was followed directly by a forget cue thereby reducing the need to remember the initial set of six memory items by three. In the set-size 6-3 condition, participants performed just as well on the later WM test of the cued to-be-remembered (TBR) items as in the set-size 3 baseline. Oberauer (2018) concluded that thus the memory items had been removed instantaneously and completely from WM. While studies of directed forgetting (DF) in long-term memory and WM use similar methods to induce forgetting (i.e., remember/forget cues in the list-method or item-method of DF), they test for the effectiveness of forgetting in different ways: WM studies assess it only indirectly by showing that access to TBR items (or encoding of new content) is facilitated (see also Lewis-Peacock et al., 2018). Episodic-memory studies on the other hand usually gauge the availability of to-be-forgotten (TBF) information directly through a surprise test. The fact that the retrieval performance for TBF items has not been directly assessed – a notable exception to this is a study on visual WM (Williams et al., 2013; yet, only using two TBR objects) – is particularly striking as testing the TBF items in a surprise test is the basis for DF paradigms in long-term memory. The proposed project aims to shed new light on what happens with the mental representations of stimuli in WM when they are cued to be forgotten, by testing their availability directly. In particular, we will test to what extent people selectively remove irrelevant information from WM by combining the DF paradigm used in long-term memory studies (e.g., Bjork, 1970) with the item-removal paradigm in WM (Oberauer, 2018). To gauge memory for the TBF words directly, on a small subset of trials we will probe one of the TBF words in one of the TBF frames. We will refer to this surprise test as a TBF test. Doing this raises a methodological challenge: Once participants are tested for items that they were instructed to forget, they may start to ignore the forget cues (see Williams & Woodman, 2012). Prior research (Muter, 1980; Williams et al., 2013) showed that TBF items are very effectively forgotten when tested on only 1-2% of trials. Work by Dagry and Barrouillet (2017) suggests that even material tested on >20% of trials is effectively forgotten. To assess how often we can test TBF items without undermining the forget instruction, we will vary the frequency with which the TBF items are tested (5%, 10%, or 20% of all trials) between participants and assess the stability of DF effects. In sum, this experiment will allow us to directly assess whether TBF items are no longer available in WM and can thus not be retrieved in recognition tests (i.e., accuracy for TBF items should be close to chance).

Memory plays a major but underexplored role in judgment and decision making (JDM). Studying eye movements-especially how people look at empty spatial locations when retrieving from memory information previously associated with those locations-provides useful information about how memory influences JDM. This so-called looking-at-nothing behavior is thought to reflect memory-driven allocation of attention. However, eye movements are also guided toward salient visual stimuli, such as test items presented on a screen. It is unclear how these multiple sources of activation combine to guide looking-at-nothing in JDM. We investigated this question in two experiments in which participants solved multiattribute categorization tasks using an exemplar-based decision strategy. In the first experiment, we tested how the occurrence and the strength of looking-at-nothing vary with the presentation format and the amount of training participants received. Looking-at-nothing occurred during categorizations when test-item information was presented auditorily and visually, but for the latter only after visual information was removed from the screen. It occurred both when training items were learned by heart and when they were presented 10 times on the screen. A second experiment revealed that an explicit instruction to imagine retrieval-relevant information during categorizations increased looking-at-nothing but did not change the decision-making process. The results shed light on the interaction between eye movements and attention to information in memory during JDM that can be explained in light of a shared priority map in memory. A detailed understanding of this interaction forms the basis for using eye movements to study memory processes in JDM. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Background Understanding the development of the neuronal circuitry underlying autism spectrum disorder (ASD) is critical to shed light into its etiology and for the development of treatment options. Resting state EEG provides a window into spontaneous local and long-range neuronal synchronization and has been investigated in many ASD studies, but results are inconsistent. Unbiased investigation in large and comprehensive samples focusing on replicability is needed. Methods We quantified resting state EEG alpha peak metrics, power spectrum (PS, 2–32 Hz) and functional connectivity (FC) in 411 children, adolescents and adults (n = 212 ASD, n = 199 neurotypicals [NT], all with IQ > 75). We performed analyses in source-space using individual head models derived from the participants’ MRIs. We tested for differences in mean and variance between the ASD and NT groups for both PS and FC using linear mixed effects models accounting for age, sex, IQ and site effects. Then, we used machine learning to assess whether a multivariate combination of EEG features could better separate ASD and NT participants. All analyses were embedded within a train-validation approach (70%–30% split). Results In the training dataset, we found an interaction between age and group for the reactivity to eye opening (p = .042 uncorrected), and a significant but weak multivariate ASD vs. NT classification performance for PS and FC (sensitivity 0.52–0.62, specificity 0.59–0.73). None of these findings replicated significantly in the validation dataset, although the effect size in the validation dataset overlapped with the prediction interval from the training dataset. Limitations The statistical power to detect weak effects—of the magnitude of those found in the training dataset—in the validation dataset is small, and we cannot fully conclude on the reproducibility of the training dataset’s effects. Conclusions This suggests that PS and FC values in ASD and NT have a strong overlap, and that differences between both groups (in both mean and variance) have, at best, a small effect size. Larger studies would be needed to investigate and replicate such potential effects., Molecular Autism, 13

The present research (total N = 2,057) tested whether people’s folk conception of consciousness aligns with the notion of a “Cartesian Theater” (Dennett, 1991). More precisely, we tested the hypotheses that people believe that consciousness happens in a single, confined area (vs. multiple dispersed areas) in the human brain, and that it (partly) happens after the brain finished analyzing all available information. Further, we investigated how these beliefs are related to participants’ neuroscientific knowledge as well as their reliance on intuition, and which rationale they use to explain their responses. Using a computer-administered drawing task, we found that participants located consciousness, but not unrelated neurological processes (Studies 1a & 1b) or unconscious thinking (Study 2) in a single, confined area in the prefrontal cortex, and that they considered most of the brain not involved in consciousness. Participants mostly relied on their intuitions when responding, and they were not affected by prior knowledge about the brain. Additionally, they considered the conscious experience of sensory stimuli to happen in a spatially more confined area than the corresponding computational analysis of these stimuli (Study 3). Furthermore, participants’ explicit beliefs about spatial and temporal localization of consciousness (i.e., consciousness happening after the computational analysis of sensory information is completed) are independent, yet positively correlated beliefs (Study 4). Using a more elaborate measure for temporal localization of conscious experience, our final study confirmed that people believe consciousness to partly happen even after information processing is done (Study 5).

Background Disturbances in the brain fluid balance can lead to life-threatening elevation in the intracranial pressure (ICP), which represents a vast clinical challenge. Nevertheless, the details underlying the molecular mechanisms governing cerebrospinal fluid (CSF) secretion are largely unresolved, thus preventing targeted and efficient pharmaceutical therapy of cerebral pathologies involving elevated ICP. Methods Experimental rats were employed for in vivo determinations of CSF secretion rates, ICP, blood pressure and ex vivo excised choroid plexus for morphological analysis and quantification of expression and activity of various transport proteins. CSF and blood extractions from rats, pigs, and humans were employed for osmolality determinations and a mathematical model employed to determine a contribution from potential local gradients at the surface of choroid plexus. Results We demonstrate that CSF secretion can occur independently of conventional osmosis and that local osmotic gradients do not suffice to support CSF secretion. Instead, the CSF secretion across the luminal membrane of choroid plexus relies approximately equally on the Na+/K+/2Cl− cotransporter NKCC1, the Na+/HCO3− cotransporter NBCe2, and the Na+/K+-ATPase, but not on the Na+/H+ exchanger NHE1. We demonstrate that pharmacological modulation of CSF secretion directly affects the ICP. Conclusions CSF secretion appears to not rely on conventional osmosis, but rather occur by a concerted effort of different choroidal transporters, possibly via a molecular mode of water transport inherent in the proteins themselves. Therapeutic modulation of the rate of CSF secretion may be employed as a strategy to modulate ICP. These insights identify new promising therapeutic targets against brain pathologies associated with elevated ICP.

BackgroundWays to prevent disease-induced vascular modifications that accelerate brain damage remain largely elusive. Improved understanding of perivascular cell signalling could provide unparalleled insight as these cells impact vascular stability and functionality of the neurovascular unit as a whole. Identifying key drivers of astrocyte and pericyte responses that modify cell–cell interactions and crosstalk during injury is key. At the cellular level, injury-induced outcomes are closely entwined with activation of the hypoxia-inducible factor-1 (HIF-1) pathway. Studies clearly suggest that endothelial HIF-1 signalling increases blood–brain barrier permeability but the influence of perivascular HIF-1 induction on outcome is unknown. Using novel mouse lines with astrocyte and pericyte targeted HIF-1 loss of function, we herein show that vascular stability in vivo is differentially impacted by perivascular hypoxia-induced HIF-1 stabilization.MethodsTo facilitate HIF-1 deletion in adult mice without developmental complications, novel Cre-inducible astrocyte-targeted (GFAP-CreERT2; HIF-1αfl/fland GLAST-CreERT2; HIF-1αfl/fl) and pericyte-targeted (SMMHC-CreERT2; HIF-1αfl/fl) transgenic animals were generated. Mice in their home cages were exposed to either normoxia (21% O2) or hypoxia (8% O2) for 96 h in an oxygen-controlled humidified glove box. All lines were similarly responsive to hypoxic challenge and post-Cre activation showed significantly reduced HIF-1 target gene levels in the individual cells as predicted.ResultsUnexpectedly, hypoxia-induced vascular remodelling was unaffected by HIF-1 loss of function in the two astrocyte lines but effectively blocked in the pericyte line. In correlation, hypoxia-induced barrier permeability and water accumulation were abrogated only in pericyte targeted HIF-1 loss of function mice. In contrast to expectation, brain and serum levels of hypoxia-induced VEGF, TGF-β and MMPs (genes known to mediate vascular remodelling) were unaffected by HIF-1 deletion in all lines. However, in agreement with the permeability data, immunofluorescence and electron microscopy showed clear prevention of hypoxia-induced tight junction disruption in the pericyte loss of function line.ConclusionThis study shows that pericyte but not astrocyte HIF-1 stabilization modulates endothelial tight junction functionality and thereby plays a pivotal role in hypoxia-induced vascular dysfunction. Whether the cells respond similarly or differentially to other injury stimuli will be of significant relevance.

Repeated exposure is assumed to promote long-term learning. This is demonstrated by the so-called "Hebb-effect": when short lists of verbal or spatial materials are presented sequentially for an immediate serial recall test, recall improves with list repetition. This repetition benefit, however, is not ubiquitous. Previous studies found little or no performance improvement for repetitions of visuospatial arrays (e.g., arrays of colored squares). Across eight experiments with college students and Prolific samples, we investigated which factors promote visuospatial learning by testing all combinations of variables distinguishing between visual-array tasks (brief + simultaneous presentation + a single recognition test) and tasks showing the Hebb effect (slow + sequential presentation + recall test probing all items). Participants profited from repetitions when all items were tested with a recall procedure, but not if the test consisted of recognition. Hence, the key to promote long-term learning is to recall all of the memorized information over the short-term. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

The increasing global prevalence of dementia demands concrete actions that are aimed strategically at optimizing processes that drive clinical innovation. The first step in this direction requires outlining hurdles in the transition from research to practice. The different parties needed to support translational processes have communication mismatches; methodological gaps hamper evidence-based decision-making; and data are insufficient to provide reliable estimates of long-term health benefits and costs in decisional models. Pilot projects are tackling some of these gaps, but appropriate methods often still need to be devised or adapted to the dementia field. A consistent implementation perspective along the whole translational continuum, explicitly defined and shared among the relevant stakeholders, should overcome the "research-versus-adoption" dichotomy, and tackle the implementation cliff early on. Concrete next steps may consist of providing tools that support the effective participation of heterogeneous stakeholders and agreeing on a definition of clinical significance that facilitates the selection of proper outcome measures.

Although innumerable studies using an auditory sensory gating paradigm have confirmed that individuals with schizophrenia (SZ) show less reduction in brain response to the second in a pair of clicks, this large literature has not yielded consensus on the circuit(s) responsible for gating nor for the gating difference in SZ. Clinically stable adult inpatients (N = 157) and matched community participants (N = 90) participated in a standard auditory sensory gating protocol. Responses to paired clicks were quantified as peak-to-peak amplitude from a response at approximately 50 ms to a response at approximately 100 ms in MEG-derived source waveforms. For bilateral sources in each of four regions near Heschl's gyrus, the gating ratio was computed as the response to the second stimulus divided by the response to the first stimulus. Spectrally resolved Granger causality quantified effective connectivity among regions manifested in alpha-band oscillatory coupling before and during stimulation. Poorer sensory gating localized to A1 in SZ than in controls confirmed previous results, here found in adjacent brain regions as well. Spontaneous, stimulus-independent effective connectivity within the hemisphere from angular gyrus to portions of the superior temporal gyrus was lower in SZ and correlated with gating ratio. Significant involvement of frontal and subcortical brain regions previously proposed as contributing to the auditory gating abnormality was not found. Findings point to endogenous connectivity evident in a sequence of activity from angular gyrus to portions of superior temporal gyrus as a mechanism contributing to normal and abnormal gating in SZ and potentially to sensory and cognitive symptoms.

A systematic review of the psychometric properties and feasibility of outcome measures assessing lower limb somatosensory function and body awareness in children with upper motor neuron lesion.We followed the COnsensus-based Standards for the selection of health Measurement INstruments guidelines. Two raters independently judged the quality and risk of bias of each study. Data synthesis was performed, and aspects of feasibility were extracted.Twelve studies investigated eleven somatosensory function measures quantifying four modalities and eight body awareness measures quantifying two modalities. The best evidence synthesis was very low to low for somatosensory function modalities and low for body awareness modalities. Few feasibility aspects were reported (e.g., the percentage or minimum age of participants able to perform the tests).Current evidence on the psychometric characteristics of somatosensory function and body awareness outcome measures are relatively sparse. Further research on psychometric properties and practical application is needed.

AIM To investigate neurodevelopmental outcome of children with open prenatal spina bifida aperta (SBA) repair. METHOD Prenatal SBA repair was performed in 130 fetuses at the Zurich Center between 2010 and 2019. Seventy-seven children underwent 1 year assessment with the Griffiths Mental Developmental Scales (Griffiths) and 65 with the Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III) at 2 years. Anatomical and functional level and ambulation status were assessed. Descriptive statistics and multiple linear regression analyses for risk factors were performed. RESULTS The Bayley-III cognition composite score in children with prenatal SBA repair was within normal limits but lower compared to population norms (mean=95.15, SD=14.683 vs norm=100, SD=15, p=0.01). Fine motor development (mean=9.58, SD=2.744, p=0.227) was typical while gross motor development was lower than the norm (mean=3.02, SD=2.758 vs norm=10, SD=3, p

Being securely attached and willing to forgive your partner tends to promote greater relationship success. Though attachment and partner forgiveness are associated cross-sectionally, research has yet to investigate whether and how these positive relationship factors tend to codevelop over time. The current study examined cross-lagged effects and correlated changes in partner forgivingness and attachment across a 2-year period with two measurement occasions ( n = 514 individuals). Additionally, dyadic analyses were conducted with a subsample of dyads in the study ( n = 149 dyads). Individual level analyses evidenced negative cross-sectional and longitudinal associations between attachment-anxiety and forgivingness. Attachment-avoidance and forgivingness showed significant correlated changes over time. Dyadic level analyses showed that attachment-avoidance predicted partner forgivingness 2 years later but not vice versa. Findings suggest that longitudinal associations between attachment and forgivingness may take different forms at the individual and dyadic level.

Adolescence represents a time of significant change in emotional processes. To what extent these changes in emotional processes are similar or distinct in adolescents relative to young adults remains largely unknown. The current study tested whether variation in reaction times to emotional stimuli could distinguish between different phases of emotional development. Ex-Gaussian parameters mu, sigma and tau were computed, in addition to mean, median and standard deviation (SD) in reaction times (RT) during an emotional go/nogo-paradigm with fearful, happy and calm facial expressions in 377 participants, 6 to 30 years of age. Mean RT showed consistent slowing to fearful expressions relative to both calm and positive cues across development, but mu revealed that this pattern was more specific to adolescence. In contrast, increased variability to fearful expressions relative to both happy and calm ones was captured by SD and tau and specific to young adulthood. The findings suggest that in adolescents and young adults response speed and variability are differentially modulated by negative emotional information, possibly reflecting distinct phases of the development of emotional processing. Understanding age specific changes in negative emotional processes ultimately may inform our understanding of the emergence of different psychopathologies in adolescence and in early adulthood.

Background Genetic variation in a population has an influence on the manifestation of monogenic as well as multifactorial disorders, with the underlying genetic contribution dependent on several interacting variants. Common laboratory mouse strains used for modelling human disease lack the genetic variability of the human population. Therefore, outcomes of rodent studies show limited relevance to human disease. The functionality of brain vasculature is an important modifier of brain diseases. Importantly, the restrictive interface between blood and brain—the blood–brain barrier (BBB) serves as a major obstacle for the drug delivery into the central nervous system (CNS). Using genetically diverse mouse strains, we aimed to investigate the phenotypic and transcriptomic variation of the healthy BBB in different inbred mouse strains. Methods We investigated the heterogeneity of brain vasculature in recently wild-derived mouse strains (CAST/EiJ, WSB/EiJ, PWK/PhJ) and long-inbred mouse strains (129S1/SvImJ, A/J, C57BL/6J, DBA/2J, NOD/ShiLtJ) using different phenotypic arms. We used immunohistochemistry and confocal laser microscopy followed by quantitative image analysis to determine vascular density and pericyte coverage in two brain regions—cortex and hippocampus. Using a low molecular weight fluorescence tracer, sodium fluorescein and spectrophotometry analysis, we assessed BBB permeability in young and aged mice of selected strains. For further phenotypic characterization of endothelial cells in inbred mouse strains, we performed bulk RNA sequencing of sorted endothelial cells isolated from cortex and hippocampus. Results Cortical vessel density and pericyte coverage did not differ among the investigated strains, except in the cortex, where PWK/PhJ showed lower vessel density compared to NOD/ShiLtJ, and a higher pericyte coverage than DBA/2J. The vascular density in the hippocampus differed among analyzed strains but not the pericyte coverage. The staining patterns of endothelial arteriovenous zonation markers were similar in different strains. BBB permeability to a small fluorescent tracer, sodium fluorescein, was also similar in different strains, except in the hippocampus where the CAST/EiJ showed higher permeability than NOD/ShiLtJ. Transcriptomic analysis of endothelial cells revealed that sex of the animal was a major determinant of gene expression differences. In addition, the expression level of several genes implicated in endothelial function and BBB biology differed between wild-derived and long-inbred mouse strains. In aged mice of three investigated strains (DBA/2J, A/J, C57BL/6J) vascular density and pericyte coverage did not change—expect for DBA/2J, whereas vascular permeability to sodium fluorescein increased in all three strains. Conclusions Our analysis shows that although there were no major differences in parenchymal vascular morphology and paracellular BBB permeability for small molecular weight tracer between investigated mouse strains or sexes, transcriptomic differences of brain endothelial cells point to variation in gene expression of the intact BBB. These baseline variances might be confounding factors in pathological conditions that may lead to a differential functional outcome dependent on the sex or genetic polymorphism.

Embodiment research is at a turning point. There is an increasing amount of data and studies investigating embodiment phenomena and their role in mental processing and functions from across a wide range of disciplines and theoretical schools within the life sciences. However, the integration of behavioral data with data from different biological levels is challenging for the involved research fields such as movement psychology, social and developmental neuroscience, computational psychosomatics, social and behavioral epigenetics, human-centered robotics, and many more. This highlights the need for an interdisciplinary framework of embodiment research. In addition, there is a growing need for a cross-disciplinary consensus on level-specific criteria of embodiment. We propose that a developmental perspective on embodiment is able to provide a framework for overcoming such pressing issues, providing analytical tools to link timescales and levels of embodiment specific to the function under study, uncovering the underlying developmental processes, clarifying level-specific embodiment criteria, and providing a matrix and platform to bridge disciplinary boundaries among the involved research fields., Frontiers in Systems Neuroscience, 15, ISSN:1662-5137

The interest in lysergic acid diethylamide (LSD) has sparked again due to its supposed positive effects on psychopathological conditions. Yet, most research focuses on the actions of LSD on the central nervous system. The interaction with the autonomic nervous system (ANS) has been neglected so far. Therefore, the aim was to assess the effects of LSD and the serotonin 2A receptor antagonist ketanserin on the ANS as assessed by heart rate variability (HRV) measures and their correlation with subjective drug-induced effects in a randomized, placebo-controlled crossover trial. Thus, ANS activity was derived from electrocardiogram recordings after intake of placebo, LSD or ketanserin, and LSD by calculating R-peak-based measures of sympathetic and parasympathetic activity. Repeated measure ANOVA and partial correlation for HRV measures and subjective experience questionnaires were performed. LSD predominantly increased sympathetic activity, while ketanserin counteracted this effect on the ANS via an increase of parasympathetic tone. Sympathetic activity was positively and parasympathetic activity negatively associated with psychedelic effects of LSD. Furthermore, Placebo HRV measures predicted subjective experiences after LSD intake. The association between trait ANS activity and LSD-induced subjective experiences may serve as a candidate biomarker set for the effectiveness of LSD in the treatment of psychopathological conditions.

Background Astrocytes (AC) are essential for brain homeostasis. Much data suggests that AC support and protect the vascular endothelium, but increasing evidence indicates that during injury conditions they may lose their supportive role resulting in endothelial cell activation and BBB disturbance. Understanding the triggers that flip this switch would provide invaluable information for designing new targets to modulate the brain vascular compartment. Hypoxia-inducible factor-1 (HIF-1) has long been assumed to be a culprit for barrier dysfunction as a number of its target genes are potent angiogenic factors. Indeed AC themselves, reservoirs of an array of different growth factors and molecules, are frequently assumed to be the source of such molecules although direct supporting evidence is yet to be published. Being well known reservoirs of HIF-1 dependent angiogenic molecules, we asked if AC HIF-1 dependent paracrine signaling drives brain EC disturbance during hypoxia. Methods First we collected conditioned media from control and siRNA-mediated HIF-1 knockdown primary rat AC that had been exposed to normoxic or hypoxic conditions. The conditioned media was then used to culture normoxic and hypoxic (1% O2) rat brain microvascular EC (RBE4) for 6 and 24 h. Various activation parameters including migration, proliferation and cell cycling were assessed and compared to untreated controls. In addition, tight junction localization and barrier stability per se (via permeability assay) was evaluated. Results AC conditioned media maintained both normoxic and hypoxic EC in a quiescent state by suppressing EC metabolic activity and proliferation. By FACs we observed reduced cell cycling with an increased number of cells in G0 phase and reduced cell numbers in M phase compared to controls. EC migration was also blocked by AC conditioned media and in correlation hypoxic tight junction organization and barrier functionality was improved. Surprisingly however, AC HIF-1 deletion did not impact EC responses or barrier stability during hypoxia. Conclusions This study demonstrates that AC HIF-1 dependent paracrine signaling does not contribute to AC modulation of EC barrier function under normoxic or hypoxic conditions. Thus other cell types likely mediate EC permeability in stress scenarios. Our data does however highlight the continuous protective effect of AC on the barrier endothelium. Exploring these protective mechanisms in more detail will provide essential insight into ways to prevent barrier disturbance during injury and disease.

Reward magnitude is a central concept in most theories of preferential decision making and learning. However, it is unknown whether variable rewards also influence cognitive processes when learning how to make accurate decisions (e.g., sorting healthy and unhealthy food differing in appeal). To test this, we conducted 3 studies. Participants learned to classify objects with 3 feature dimensions into two categories before solving a transfer task with novel objects. During learning, we rewarded all correct decisions, but specific category exemplars yielded a 10 times higher reward (high vs. low). Counterintuitively, categorization performance did not increase for high-reward stimuli, compared with an equal-reward baseline condition. Instead, performance decreased reliably for low-reward stimuli. To analyze the influence of reward magnitude on category generalization, we implemented an exemplar-categorization model and a cue-weighting model using a Bayesian modeling approach. We tested whether reward magnitude affects (a) the availability of exemplars in memory, (b) their psychological similarity to the stimulus, or (c) attention to stimulus features. In all studies, the evidence favored the hypothesis that reward magnitude affects the similarity gradients of high-reward exemplars compared with the equal-reward baseline. The results from additional reward-judgment tasks (Studies 2 and 3) strongly suggest that the cognitive processes of reward-value generalization parallel those of category generalization. Overall, the studies provide insights highlighting the need for integrating reward- and category-learning theories. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

The ability to infer mental and affective states of others is crucial for social functioning. This ability, denoted as Theory of Mind (ToM), develops rapidly during childhood, yet results on its development across adolescence and into young adulthood are rare. In the present study, we tested the two‐component model, measuring age‐related changes in social‐perceptual and social‐cognitive ToM in a sample of 267 participants between 11 and 25 years of age. Additionally, we measured language, reasoning, and inhibitory control as major covariates. Participants inferred mental states from non‐verbal cues in a social‐perceptual task (Eye Test) and from stories with faux pas in a social‐cognitive task (Faux Pas Test). Results showed substantial improvement across adolescence in both ToM measures and in the covariates. Analysis with linear mixed models (LMM) revealed specific age‐related growth for the social‐perceptual component, while the age‐related increase of the social‐cognitive component fully aligned with the increase of the covariates. These results support the distinction between ToM components and indicate that adolescence is a crucial period for developing social‐perceptual ToM abilities., British Journal of Developmental Psychology, 38 (2), ISSN:0261-510X, ISSN:2044-835X

Traumatic experiences are common and linked to cardiovascular disease (CVD) risk, yet the mechanisms underlying these relationships is less well understood. Few studies have examined trauma exposure and its relation to autonomic influence over cardiac function, a potential pathway linking trauma exposure to CVD risk. Investigating autonomic influence over cardiac function during both wake and sleep is critical, given particular links of sleep autonomic function to cardiovascular health. Among midlife women, we tested whether trauma exposure would be related to lower high frequency heart rate variability (HF-HRV), an index of vagal influence over cardiac function, during wake and sleep. Three hundred and one nonsmoking midlife women completed physical measures, a 24-hr electrocardiogram, actigraphy sleep measurement, and questionnaires about trauma (Brief Trauma Questionnaire), childhood abuse (Child Trauma Questionnaire [CTQ]), mood, demographics, and medical/psychiatric history. Relations between trauma and HF-HRV were assessed in linear mixed effects models adjusting for covariates (age, race, education, body mass index, blood pressure, psychiatric history, medication use, sleep, mood, childhood abuse history). Results indicated that most women had experienced trauma. Any trauma exposure as well as a greater number of traumatic experiences were associated with lower HF-HRV during wake and particularly during sleep. Relations were not accounted for by covariates. Among midlife women, trauma exposure was related to lower HF-HRV during wake and sleep. Trauma may have an important impact on vagal influence over the heart, particularly during sleep. Decreased vagal influence over cardiac function may be a key mechanism by which trauma is associated with CVD risk.