Brain hubs defined in the group do not overlap with regions of high inter-individual variability.

Connector 'hubs' are brain regions with links to multiple networks. These regions are hypothesized to play a critical role in brain function. While hubs are often identified based on group-average functional magnetic resonance imaging (fMRI) data, there is considerable inter-subject variation in the functional connectivity profiles of the brain, especially in association regions where hubs tend to be located. Here we investigated how group hubs are related to locations of inter-individual variability. To answer this question, we examined inter-individual variation at group-level hubs in both the Midnight Scan Club and Human Connectome Project datasets. The top group hubs defined based on the participation coefficient did not overlap strongly with the most prominent regions of inter-individual variation (termed 'variants' in prior work). These hubs have relatively strong similarity across participants and consistent cross-network profiles, similar to what was seen for many other areas of cortex. Consistency across participants was further improved when these hubs were allowed to shift slightly in local position. Thus, our results demonstrate that the top group hubs defined with the participation coefficient are generally consistent across people, suggesting they may represent conserved cross-network bridges. More caution is warranted with alternative hub measures, such as community density (which are based on spatial proximity to network borders) and intermediate hub regions which show higher correspondence to locations of individual variability.

WITHDRAWN: The interaction between random and systematic visual stimulation and infraslow quasiperiodic spatiotemporal patterns of whole brain activity.

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Beyond mind wandering: Performance variability and neural activity during off-task thought and other attention lapses.

To study the characteristics of attention lapses, a metronome response task and experience sampling were employed while recording fMRI data. Thought prompts queried several attention states (on-task, task-related interference, off-task, inattention). Off-task thoughts were probed on whether they arose in a spontaneous or constrained (i.e., directed) manner. Increased fMRI activation was observed in the default mode network during off-task thought and in subregions of the anterior cingulate cortex and inferior frontal gyrus during inattention. Activation also increased in the left hippocampus during constrained thoughts. Functional connectivity increased between the left superior temporal sulcus and right temporoparietal junction for constrained compared to spontaneous thoughts. Overall, behavioral results indicated a monotonic increase in performance variability from on-task to inattention. However, subtle but consistent differences were observed between self-reported attention state and performance. Results are discussed from perspectives of mind wandering frameworks, the function of brain networks, and the role of engagement in off-task thought.

BOLD cofluctuation 'events' are predicted from static functional connectivity.

Recent work identified single time points ("events") of high regional cofluctuation in functional Magnetic Resonance Imaging (fMRI) which contain more large-scale brain network information than other, low cofluctuation time points. This suggested that events might be a discrete, temporally sparse signal which drives functional connectivity (FC) over the timeseries. However, a different, not yet explored possibility is that network information differences between time points are driven by sampling variability on a constant, static, noisy signal. Using a combination of real and simulated data, we examined the relationship between cofluctuation and network structure and asked if this relationship was unique, or if it could arise from sampling variability alone. First, we show that events are not discrete - there is a gradually increasing relationship between network structure and cofluctuation; ∼50% of samples show very strong network structure. Second, using simulations we show that this relationship is predicted from sampling variability on static FC. Finally, we show that randomly selected points can capture network structure about as well as events, largely because of their temporal spacing. Together, these results suggest that, while events exhibit particularly strong representations of static FC, there is little evidence that events are unique timepoints that drive FC structure. Instead, a parsimonious explanation for the data is that events arise from a single static, but noisy, FC structure.

Exercise-induced bronchoconstriction in elite or endurance athletes:: Pathogenesis and diagnostic considerations.

OBJECTIVE: To review the pathogenesis and evaluation of exercise-induced bronchoconstriction pertaining to the elite or endurance athlete, as well as propose a diagnostic algorithm based on the current literature. DATA SOURCES: Studies were identified using Ovid MEDLINE and reference lists of key articles. STUDY SELECTIONS: Randomized controlled trials were selected when available. Systematic reviews and meta-analyses of peer-reviewed literature were included, as were retrospective studies and observational studies of clinical interest. RESULTS: Exercise-induced bronchoconstriction (EIB) is the physiologic entity in which exercise induces acute narrowing of the airways and occurs in patients both with and without asthma. It may present with or without respiratory symptoms, and the underlying cause is likely attributable to environment stressors to the airway encountered during exercise. These include the osmotic effects of inhaled dry air, temperature variations, autonomic nervous system dysregulation, sensory nerve reactivity, and airway epithelial injury. Deposition of allergens, particulate matter, and gaseous pollutants into the airway also contribute. Elite and endurance athletes are exposed to these stressors more frequently and in greater duration than the general population. CONCLUSION: A greater awareness of EIB among elite and endurance athletes is needed, and a thorough evaluation should be performed if EIB is suspected in this population. We propose an algorithm to aid in this evaluation. Symptoms should not be solely relied on for diagnosis but should be taken into the context of bronchoprovocative challenges, which should replicate the competitive environment as closely as possible. Further research is needed to validate these tests' predictive values.

Genomic sequencing of uric acid metabolizing and clearing genes in relationship to xanthine oxidase inhibitor dose.

It remains unclear why the dose of xanthine oxidase inhibitors (XOI) allopurinol or febuxostat varies among patients though they reach similar serum uric acid (SUA) goal. We pursued genomic sequencing of XOI metabolism and clearance genes to identify single-nucleotide polymorphisms (SNPs) relate to differences in XOI dose. Subjects with a diagnosis of Gout based on the 1977 American College of Rheumatology Classification Criteria for the disorder, who were on stable doses of a XOI, and who were at their goal SUA level, were enrolled. The primary outcome was relationship between SNPs in any of these genes to XOI dose. The secondary outcome was relationship between SNPs and change in pre- and post-treatment SUA. We enrolled 100 subjects. The average patient age was 68.6 ± 10.6 years old. Over 80% were men and 77% were Caucasian. One SNP was associated with a higher XOI dose: rs75995567 (p = 0.031). Two SNPs were associated with 300 mg daily of allopurinol: rs11678615 (p = 0.022) and rs3731722 on Aldehyde Oxidase (AO) (His1297Arg) (p = 0.001). Two SNPs were associated with a lower dose of allopurinol: rs1884725 (p = 0.033) and rs34650714 (p = 0.006). For the secondary outcome, rs13415401 was the only SNP related to a smaller mean SUA change. Ten SNPs were identified with a larger change in SUA. Though multiple SNPs were identified in the primary and secondary outcomes of this study, rs3731722 is known to alter catalytic function for some aldehyde oxidase substrates.

Dog allergen immunotherapy: past, present, and future.

OBJECTIVE: To review the published medical literature on dog allergy immunotherapy and discuss prior clinical trials, important allergens, extract specifics, and potential future treatment options for dog allergy relevant to the clinical allergist. DATA SOURCES: MEDLINE search was performed using the terms dog, immunotherapy, and allergy limited to human studies from any period. Articles cited in selected studies also were reviewed for appropriateness of inclusion into this review. STUDY SELECTIONS: Publications were included that were original research and fit the topic of dog allergen immunotherapy, specifically articles that investigated prior effectiveness and safety of dog allergen immunotherapy, dog extracts, identification of dog allergens, and current prescribing trends among allergists. RESULTS: Two hundred fifteen articles were initially identified and 60 were reviewed in complete detail for inclusion in this review. The primary focus was placed on the 17 clinical trials that investigated the safety and efficacy of dog immunotherapy and the 19 studies that explored and defined the complex allergenic profile of dog extracts. CONCLUSION: The medical literature on the use of dog extract immunotherapy in patients with hypersensitivity to dog shows poor and conflicting results of clinical efficacy, which has been attributed to poor-quality extracts and the inherent complex allergenic profile of dogs that remains without a clearly dominant allergen.

Two common and distinct forms of variation in human functional brain networks.

The cortex has a characteristic layout with specialized functional areas forming distributed large-scale networks. However, substantial work shows striking variation in this organization across people, which relates to differences in behavior. While most previous work treats individual differences as linked to boundary shifts between the borders of regions, here we show that cortical 'variants' also occur at a distance from their typical position, forming ectopic intrusions. Both 'border' and 'ectopic' variants are common across individuals, but differ in their location, network associations, properties of subgroups of individuals, activations during tasks, and prediction of behavioral phenotypes. Border variants also track significantly more with shared genetics than ectopic variants, suggesting a closer link between ectopic variants and environmental influences. This work argues that these two dissociable forms of variation-border shifts and ectopic intrusions-must be separately accounted for in the analysis of individual differences in cortical systems across people.

Pedunculopontine-induced cortical decoupling as the neurophysiological locus of dissociation.

Mounting evidence suggests an association between aberrant sleep phenomena and dissociative experiences. However, no wake-sleep boundary theory provides a compelling explanation of dissociation or specifies its physiological substrates. We present a theoretical account of dissociation that integrates theories and empirical results from multiple lines of research concerning the domain of dissociation and the regulation of rapid eye movement (REM) sleep. This theory posits that individual differences in the circuitry governing the REM sleep promoting Pedunculopontine Nucleus and Laterodorsal Tegmental Nucleus determine the degree of similarity in the cortical connectivity profiles of wakefulness and REM sleep. We propose that a latent trait characterized by elevated dissociative experiences emerges from the decoupling of frontal executive regions due to a REM sleep-like aminergic/cholinergic balance. The Pedunculopontine-Induced Cortical Decoupling Account of Dissociation (PICDAD) suggests multiple fruitful lines of inquiry and provides novel insights. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

From correlation to communication: Disentangling hidden factors from functional connectivity changes.

While correlations in the BOLD fMRI signal are widely used to capture functional connectivity (FC) and its changes across contexts, its interpretation is often ambiguous. The entanglement of multiple factors including local coupling of two neighbors and nonlocal inputs from the rest of the network (affecting one or both regions) limits the scope of the conclusions that can be drawn from correlation measures alone. Here we present a method of estimating the contribution of nonlocal network input to FC changes across different contexts. To disentangle the effect of task-induced coupling change from the network input change, we propose a new metric, "communication change," utilizing BOLD signal correlation and variance. With a combination of simulation and empirical analysis, we demonstrate that (1) input from the rest of the network accounts for a moderate but significant amount of task-induced FC change and (2) the proposed "communication change" is a promising candidate for tracking the local coupling in task context-induced change. Additionally, when compared to FC change across three different tasks, communication change can better discriminate specific task types. Taken together, this novel index of local coupling may have many applications in improving our understanding of local and widespread interactions across large-scale functional networks.

The interaction between random and systematic visual stimulation and infraslow quasiperiodic spatiotemporal patterns of whole brain activity.

One prominent feature of the infraslow BOLD signal during rest or task is quasi-periodic spatiotemporal pattern (QPP) of signal changes that involves an alternation of activity in key functional networks and propagation of activity across brain areas, and that is known to tie to the infraslow neural activity involved in attention and arousal fluctuations. This ongoing whole-brain pattern of activity might potentially modify the response to incoming stimuli or be modified itself by the induced neural activity. To investigate this, we presented checkerboard sequences flashing at 6Hz to subjects. This is a salient visual stimulus that is known to produce a strong response in visual processing regions. Two different visual stimulation sequences were employed, a systematic stimulation sequence in which the visual stimulus appeared every 20.3 secs and a random stimulation sequence in which the visual stimulus occurred randomly every 14~62.3 secs. Three central observations emerged. First, the two different stimulation conditions affect the QPP waveform in different aspects, i.e., systematic stimulation has greater effects on its phase and random stimulation has greater effects on its magnitude. Second, the QPP was more frequent in the systematic condition with significantly shorter intervals between consecutive QPPs compared to the random condition. Third, the BOLD signal response to the visual stimulus across both conditions was swamped by the QPP at the stimulus onset. These results provide novel insights into the relationship between intrinsic patterns and stimulated brain activity.

Measuring task structure with transitional response times: Task representations are more than task sets.

The structure of task representations is widely studied with task-switching procedures in which the experimenter compares performance across predetermined categories of trial transitions (viz., switch costs). This approach has been productive, but relies on experimental assumptions about the relationships among stimulus-response mappings that define a set. Here, we develop a novel method of evaluating structure without relying on such assumptions. Participants responded to centrally presented stimuli and we computed the transitional response times (RTs; changes in RT as a function of specific response sequences) for each response combination. Conventional task-switch analyses revealed costs when the response switched from the left-side to the right or vice versa, but this switch cost was not affected by whether the stimuli belonged to a single category or to two distinct categories. In contrast, the transitional RT analysis provided fine-grained information about relationships among responses and how these relationships were affected by stimulus and response manipulations. Specifically, tasks containing a single stimulus category produced response chains in which neighboring responses had lower transitional RTs, while these chains were broken when two stimulus categories were used. We propose that the transitional RT approach offers a more detailed picture of the underlying task representation that reveals structure not detectable by conventional switch cost measures and does not require a priori assumptions about task organization.

Quantification of COVID-19 Vaccine Needle and Syringe Dead Space Volumes.

INTRODUCTION:  The COVID-19 pandemic taught many lessons regarding vaccine manufacturing, transportation, and delivery. Throughout the vaccination campaign, different vaccination sites reported that six or seven doses of the Pfizer/BioNTech COVID-19 vaccine could be reliably withdrawn from each multidose vial. This discrepancy was hypothesized to be caused by the differences in needle and syringe dead space volumes with differing supplies utilized at each site, but independent data regarding these volumes are lacking; therefore, we sought to objectively evaluate the volume of dead space for supplies commonly used for immunizations. MATERIALS AND METHODS: Available needles and syringes of different brands and specifications that could be used for administering vaccines were gathered. Each needle and/or syringe was weighed with a scientific, calibrated scale upon removal from the manufacturer's packaging and then filled with distilled water to simulate standard vaccine preparation. The water was then expelled, simulating vaccination, and then reweighed on the same scientific scale. The difference between the two weights was secondary to the water remaining within the needle or syringe after the simulated use, which was equivalent to the dead space volume. RESULTS: Manufacturer design, gauge, needle length, and syringe volume separately correlate with volume differences. Intuitively, the needles and syringes with the most dead space were consistently the 1.5-inch needles and the larger volume syringes, regardless of the manufacturer. CONCLUSION: The withdrawal of individual vaccine doses from a multidose vial inevitably results in vaccine volume loss due to the dead space of needles and syringes. As such, reliably obtaining seven doses of the Pfizer/BioNTech COVID-19 vaccine is improbable without utilizing specialized low dead space supplies.

Light Through the Fog: Using Precision fMRI Data to Disentangle the Neural Substrates of Cognitive Control.

Cognitive control, the ability to engage in goal-related behavior, is linked to frontal, parietal, and cingulate brain regions. However, the underlying function(s) of these regions is still in question, with ongoing discussions about their specificity and/or multifunctionality. These brain regions are also among the most variable across individuals, which may confound multi-functionality with inter-individual heterogeneity. Precision fMRI-extended data acquisition from single individuals-allows for reliable individualized mapping of brain organization. We review examples of recent studies that use precision fMRI to surmount inter-individual variability in functional neuroanatomy. These studies provide evidence of interleaved specialized and multifunctional regions in the frontal cortex. We discuss the potential for these techniques to address outstanding controversies on the neural underpinnings of cognitive control.

Digging Deeper to Chart the Landscape of Human Brain Development.

How does brain system organization evolve during development? Cui et al. (2020) combine big and higher-precision fMRI data to find that maturational processes and cognitive ability track individual differences in the refinement of borders between brain systems.

A Case of Serum Sickness-Like Reaction in an Adult Treated with Omalizumab.

Omalizumab has been safely used to treat asthma and urticaria. We report a case of serum sickness-like reaction in a patient treated with omalizumab for chronic idiopathic urticaria/angioedema. An adult female experienced episodic urticaria/angioedema without repeatable trigger, ultimately receiving diagnosis of chronic idiopathic urticaria/angioedema. After initial treatment, attempts with escalating cetirizine and montelukast doses were unsuccessful due to sedation; she began treatment with subcutaneous omalizumab 150 mg monthly. Urticaria frequency partially improved after two injections; therefore, the dose was increased to 300 mg after four treatments. Several days after first 300 mg dose, she reported abdominal cramping, fatigue, fever, lymphadenopathy, and arthralgia. Aside from mild thrombocytosis, inflammatory markers were unremarkable, as were evaluations for infection, autoimmunity, and malignancy. Omalizumab was held with eventual improvement in symptoms, which did not return after discontinuation. Omalizumab is a helpful medication in treating atopic conditions, with at least theoretical risk of immune complex formation and tissue deposition causing serum sickness-like reaction. Although early publications showed very low adverse event rates, there have now been reports of serum sickness-like reactions in children and adults treated for asthma and urticaria. Determining true incidence is difficult, given rarity and non-specific nature. Previous reports described symptoms with initiation of medication, reproducible after reintroduction. While it remains to be determined which factors increase risk for serum sickness-like reaction to omalizumab, our report of an urticaria patient who exhibited symptoms with increasing dose contributes insight into the discussion regarding this adverse effect of an otherwise well-tolerated and important medication.

Sublingual Immunotherapy for Other Indications: Venom Large Local, Latex, Atopic Dermatitis, and Food.

There is some evidence to support the use of sublingual immunotherapy (SLIT) in food allergy, although its role is unclear. One randomized, double-blind, placebo-controlled trial supports the safe and efficacious use of dust mite SLIT in children with mild to moderate atopic dermatitis, but these data have not been confirmed. Although there are several randomized, double-blind, placebo-controlled trials to support the use of SLIT-LATEX, this product is not available in the United States and extrapolation of these effects to latex extracts is unsubstantiated. There is also insufficient evidence to support the use of SLIT for venom hypersensitivity at this time.

Task representation affects the boundaries of behavioral slowing following an error.

Researchers have recognized the role that task representation plays in our behavior for many years. However, the specific influence that the structure of one's task representation has on executive functioning has only recently been investigated. Prior research suggests that adjustments of cognitive control are affected by subtle manipulations of aspects of the stimulus-response pairs within and across task sets. This work has focused on examples of cognitive control such as response preparation, dual-task performance, and the congruency sequence effect. The current study investigates the effect of task representation on another example of control, post-error slowing. To determine if factors that influence how people represent a task affect how behavior is adjusted after an error, an adaptive attention-shifting task was developed with multiple task delimiting features. Participants were randomly assigned to a separate task set (two task sets) or an integrated task set (one task set) group. For the separate set group, the task sets switched after each trial. Results showed that only the integrated set group exhibited post-error slowing. This suggests that task representation influences the boundaries of cognitive control adjustments and has implications for our understanding of how control is organized when adjusting to errors in performance.