High prevalence of long-term olfactory disorders in healthcare workers after COVID-19: A case-control study.

BACKGROUND: More than a year after recovering from COVID-19, a large proportion of individuals, many of whom work in the healthcare sector, still report olfactory dysfunctions. However, olfactory dysfunction was common already before the COVID-19 pandemic, making it necessary to also consider the existing baseline prevalence of olfactory dysfunction. To establish the adjusted prevalence of COVID-19 related olfactory dysfunction, we assessed smell function in healthcare workers who had contracted COVID-19 during the first wave of the pandemic using psychophysical testing. METHODS: Participants were continuously tested for SARS-CoV-2 IgG antibodies since the beginning of the pandemic. To assess the baseline rate of olfactory dysfunction in the population and to control for the possibility of skewed recruitment of individuals with prior olfactory dysfunction, consistent SARS-CoV-2 IgG naïve individuals were tested as a control group. RESULTS: Fifteen months after contracting COVID-19, 37% of healthcare workers demonstrated a quantitative reduction in their sense of smell, compared to only 20% of the individuals in the control group. Fifty-one percent of COVID-19-recovered individuals reported qualitative symptoms, compared to only 5% in the control group. In a follow-up study 2.6 years after COVID-19 diagnosis, 24% of all tested recovered individuals still experienced parosmia. CONCLUSIONS: In summary, 65% of healthcare workers experienced parosmia/hyposmia 15 months after contracting COVID-19. When compared to a control group, the prevalence of olfactory dysfunction in the population increased by 41 percentage points. Parosmia symptoms were still lingering two-and-a half years later in 24% of SARS-CoV-2 infected individuals. Given the amount of time between infection and testing, it is possible that the olfactory problems may not be fully reversible in a plurality of individuals.

Nasal inhalation does not improve memory of visual repetitions.

Several studies suggest that breathing entrains neural oscillations and thereby improves visual detection and memory performance during nasal inhalation. However, the evidence for this association is mixed, with some studies finding no, minor, or opposite effects. Here, we tested whether nasal breathing phase influences memory of repeated images presented in a rapid serial visual presentation (RSVP) task. The RSVP task is ideal for studying the effects of respiratory-entrained oscillations on visual memory because it engages critical aspects of sensory encoding that depend on oscillatory activity, such as fast processing of natural images, repetition detection, memory encoding, and retrieval. It also enables the presentation of a large number of stimuli during each phase of the breathing cycle. In two separate experiments (n = 72 and n = 142, respectively) where participants were explicitly asked to breathe through their nose, we found that nasal breathing phase at target presentation did not significantly affect memory performance. An exploratory analysis in the first experiment suggested a potential benefit for targets appearing approximately 1 s after inhalation. However, this finding was not replicated in the pre-registered second experiment with a larger sample. Thus, in two large sample experiments, we found no measurable impact of breathing phase on memory performance in the RSVP task. These results suggest that the natural breathing cycle does not have a significant impact on memory for repeated images and raise doubts about the idea that visual memory is broadly affected by the breathing phase.

Induction of nitric oxide via humming does not improve short-term cognitive performance or influence emotional processing.

Nitric oxide (NO) is involved in a variety of biological functions including blood vessel dilation and neurotransmitter release. In animals, NO has been demonstrated to affect multiple behavioral outcomes, such as memory performance and arousal, whereas this link is less explored in humans. NO is created in the paranasal sinuses and studies show that humming releases paranasal NO to the nasal tract and that NO can then cross the blood brain barrier. Akin to animal models, we hypothesized that this NO may traverse into the brain and positively affect information processing. In contrast to our hypothesis, an articulatory suppression memory paradigm and a speeded detection task found deleterious effects of humming while performing the task. Likewise, we found no effect of humming on emotional processing of photos. In a fourth experiment, participants hummed before each trial in a speeded detection task, but we again found no effect on response time. In conclusion, either nasal NO does not travel to the brain, or NO in the brain does not have the expected impact on cognitive performance and emotional processing in humans. It remains possible that NO influences other cognitive processes not tested for here.

Metabolic state modulates neural processing of odors in the human olfactory bulb.

The olfactory and endocrine systems have recently been shown to reciprocally shape the homeostatic processes of energy intake. As demonstrated in animal models, the individual's metabolic state dynamically modulates how the olfactory bulb process odor stimuli using a range of endocrine signals. Here we aimed to determine whether the neural processing of odors in human olfactory bulb is modulated by metabolic state. Participants were exposed to food-associated odors, in separate sessions being hungry and sated, while neural responses from the olfactory bulb was obtained using electrobulbogram. We found significantly higher gamma power activity (51-100 Hz) in the OB's response to odors during the Hunger compared to Sated condition. Specifically, EBG gamma power were elevated while hungry already at 100 ms after odor onset, thereby suggesting intra-bulbar modulation according to metabolic state. These results demonstrate that, akin to other animal models, hunger state affects OB activity in humans. Moreover, we show that the EBG method has the potential to measure internal metabolic states and, as such, could be used to study specificities in olfactory processing of individuals suffering from pathologies such as obesity or anorexia.

Validation of French versions of the 15-item picker patient experience questionnaire for adults, teenagers, and children inpatients.

Objectives: No French validated concise scales are available for measuring the experience of inpatients in pediatrics. This study aims to adapt the adult PPE-15 to a pediatric population, and translating it in French, as well as to establish reference values for adults, teenagers, and parents of young children. Methods: Cultural adaptation involved forward and backward translations, along with pretests in all three populations. Dimensional structure and internal consistency were assessed using principal component analysis, exploratory factor analysis, and Cronbach's alpha. Construct validity was assessed by examining established associations between patient satisfaction and inpatient variables, including length of stay, and preventable readmission. Results: A total of 25,626 adults, 293 teenagers and 1,640 parents of young children completed the French questionnaires. Factor analysis supported a single dimension (Cronbach's alpha: adults: 0.85, teenagers: 0.82, parents: 0.80). Construct validity showed the expected pattern of association, with dissatisfaction correlating with patient- and stay-related factors, notably length of stay, and readmission. Conclusion: The French versions of the PPE-15 for adults, teenagers and parents of pediatric patients stand as valid and reliable instruments for gauging patient satisfaction regarding their hospital stay after discharge.

Effects of dopamine and opioid receptor antagonism on the neural processing of social and nonsocial rewards.

Rewards are a broad category of stimuli inducing approach behavior to aid survival. Extensive evidence from animal research has shown that wanting (the motivation to pursue a reward) and liking (the pleasure associated with its consumption) are mostly regulated by dopaminergic and opioidergic activity in dedicated brain areas. However, less is known about the neuroanatomy of dopaminergic and opioidergic regulation of reward processing in humans, especially when considering different types of rewards (i.e., social and nonsocial). To fill this gap of knowledge, we combined dopaminergic and opioidergic antagonism (via amisulpride and naltrexone administration) with functional neuroimaging to investigate the neurochemical and neuroanatomical bases of wanting and liking of matched nonsocial (food) and social (interpersonal touch) rewards, using a randomized, between-subject, placebo-controlled, double-blind design. While no drug effect was observed at the behavioral level, brain activity was modulated by the administered compounds. In particular, opioid antagonism, compared to placebo, reduced activity in the medial orbitofrontal cortex during consumption of the most valued social and nonsocial rewards. Dopamine antagonism, however, had no clear effects on brain activity in response to reward anticipation. These findings provide insights into the neurobiology of human reward processing and suggest a similar opioidergic regulation of the neural responses to social and nonsocial reward consumption.

Connecting genomic results for psychiatric disorders to human brain cell types and regions reveals convergence with functional connectivity.

Understanding the temporal and spatial brain locations etiological for psychiatric disorders is essential for targeted neurobiological research. Integration of genomic insights from genome-wide association studies with single-cell transcriptomics is a powerful approach although past efforts have necessarily relied on mouse atlases. Leveraging a comprehensive atlas of the adult human brain, we prioritized cell types via the enrichment of SNP-heritabilities for brain diseases, disorders, and traits, progressing from individual cell types to brain regions. Our findings highlight specific neuronal clusters significantly enriched for the SNP-heritabilities for schizophrenia, bipolar disorder, and major depressive disorder along with intelligence, education, and neuroticism. Extrapolation of cell-type results to brain regions reveals important patterns for schizophrenia with distinct subregions in the hippocampus and amygdala exhibiting the highest significance. Cerebral cortical regions display similar enrichments despite the known prefrontal dysfunction in those with schizophrenia highlighting the importance of subcortical connectivity. Using functional MRI connectivity from cases with schizophrenia and neurotypical controls, we identified brain networks that distinguished cases from controls that also confirmed involvement of the central and lateral amygdala, hippocampal body, and prefrontal cortex. Our findings underscore the value of single-cell transcriptomics in decoding the polygenicity of psychiatric disorders and offer a promising convergence of genomic, transcriptomic, and brain imaging modalities toward common biological targets.

Phase-locked breathing does not affect episodic visual recognition memory but does shape its corresponding ERPs.

Recent studies have indicated that breathing shapes the underlying oscillatory brain activity critical for episodic memory, potentially impacting memory performance. However, the literature has presented conflicting results, with some studies suggesting that nasal inhalation enhances visual memory performance, while others have failed to observe any significant effects. Furthermore, the specific influence of breathing route (nasal vs. mouth) and the precise phase of the respiratory cycle during which stimuli are presented have remained elusive. To address this, we employed a visual recognition memory (VRM) and electroencephalography paradigm in which stimuli presentation was phase-locked to either inhalation or exhalation onset, using a within-subject design where participants performed the memory task while engaging in separate sessions of nose and mouth breathing. We show that neither breathing route nor breathing phase has a significant impact on VRM performance as measured by d-prime, with the data supporting the null hypothesis. However, we did find an effect of breathing phase on response bias, with participants adopting a more conservative decision criterion during exhalation. Moreover, we found that breathing phase during memory encoding shaped the late parietal effect (LPE) amplitude, while the Frontal Negative Component (FN400) and LPE during recognition were less impacted. While our study demonstrates that breathing does not shape VRM performance, it shows that it influences brain activity, reinforcing the importance of further research to elucidate the extent of respiratory influence on perception, cognition, and behavior.

Effects of mobile phone electromagnetic fields on brain waves in healthy volunteers.

The interaction between biological tissue and electromagnetic fields (EMF) is a topic of increasing interest due to the rising prevalence of background EMF in the past decades. Previous studies have attempted to measure the effects of EMF on brainwaves using EEG recordings, but are typically hampered by experimental and environmental factors. In this study, we present a framework for measuring the impact of EMF on EEG while controlling for these factors. A Bayesian statistical approach is employed to provide robust statistical evidence of the observed EMF effects. This study included 32 healthy participants in a double-blinded crossover counterbalanced design. EEG recordings were taken from 63 electrodes across 6 brain regions. Participants underwent a measurement protocol comprising two 18-min sessions with alternating blocks of eyes open (EO) and eyes closed (EC) conditions. Group 1 (n = 16) had EMF during the first session and sham during the second session; group 2 (n = 16) had the opposite. Power spectral density plots were generated for all sessions and brain regions. The Bayesian analysis provided statistical evidence for the presence of an EMF effect in the alpha band power density in the EO condition. This measurement protocol holds potential for future research on the impact of novel transmission protocols.

Lifelong olfactory deprivation-dependent cortical reorganization restricted to orbitofrontal cortex.

Prolonged sensory deprivation has repeatedly been linked to cortical reorganization. We recently demonstrated that individuals with congenital anosmia (CA, complete olfactory deprivation since birth) have seemingly normal morphology in piriform (olfactory) cortex despite profound morphological deviations in the orbitofrontal cortex (OFC), a finding contradictory to both the known effects of blindness on visual cortex and to the sparse literature on brain morphology in anosmia. To establish whether these unexpected findings reflect the true brain morphology in CA, we first performed a direct replication of our previous study to determine if lack of results was due to a deviant control group, a confound in cross sectional studies. Individuals with CA (n = 30) were compared to age and sex matched controls (n = 30) using voxel- and surface-based morphometry. The replication results were near identical to the original study: bilateral clusters of group differences in the OFC, including CA atrophy around the olfactory sulci and volume increases in the medial orbital gyri. Importantly, no group differences in piriform cortex were detected. Subsequently, to assess any subtle patterns of group differences not detectable by our mass-univariate analysis, we explored the data from a multivariate perspective. Combining the newly collected data with data from the replicated study (CA = 49, control = 49), we performed support vector machine classification based on gray matter volume. In line with the mass-univariate analyses, the multivariate analysis could accurately differentiate between the groups in bilateral OFC, whereas the classification accuracy in piriform cortex was at chance level. Our results suggest that despite lifelong olfactory deprivation, piriform (olfactory) cortex is morphologically unaltered and the morphological deviations in CA are confined to the OFC.

Human scent as a first-line defense against disease.

Individuals may have a different body odor, when they are sick compared to healthy. In the non-human animal literature, olfactory cues have been shown to predict avoidance of sick individuals. We tested whether the mere experimental activation of the innate immune system in healthy human individuals can make an individuals' body odor be perceived as more aversive (intense, unpleasant, and disgusting). Following an endotoxin injection (lipopolysaccharide; 0.6 ng/kg) that creates a transient systemic inflammation, individuals smelled more unpleasant compared to a placebo group (saline injection). Behavioral and chemical analyses of the body odor samples suggest that the volatile components of samples from "sick" individuals changed qualitatively rather than quantitatively. Our findings support the hypothesis that odor cues of inflammation in axillary sweat are detectable just a few hours after experimental activation of the innate immune system. As such, they may trigger behavioral avoidance, hence constituting a first line of defense against pathogens of infected conspecifics.

Outdoor Cold Air Versus Room Temperature Exposure for Croup Symptoms: A Randomized Controlled Trial.

OBJECTIVES: Croup is the most common cause of acute upper airway obstruction in children. The benefits of treating croup with steroids are well established, with an onset of effect 30 minutes after administration. We investigated whether a 30-minute exposure to outdoor cold air might improve mild to moderate croup symptoms before the onset of action of steroids. METHODS: This open-label, single-center, randomized controlled trial, enrolled children aged 3 months to 10 years with croup and a Westley Croup Score (WCS) ≥2 attending a tertiary pediatric emergency department. Participants were randomized (1:1) to either a 30-minute exposure to outdoor cold (<10°C) atmospheric air or to indoor ambient room air immediately after triage and administration of a single-dose oral dexamethasone. The primary endpoint was a decrease in WCS ≥2 points from baseline at 30 minutes. Analyses were intention to treat. RESULTS: A total of 118 participants were randomly assigned to be exposed to outdoor cold air (n = 59) or indoor room temperature (n = 59). Twenty-nine of 59 children (49.2%) in the outdoor group and 14 of 59 (23.7%) in the indoor group showed a decrease in WCS ≥2 points from baseline at 30 minutes after triage (risk difference 25.4% [95% confidence interval 7.0-43.9], P = .007). Patients with moderate croup benefited the most from the intervention at 30 minutes (risk difference 46.1% [20.6-71.5], P < .001). CONCLUSIONS: A 30-minute exposure to outdoor cold air (<10°C), as an adjunct to oral dexamethasone, is beneficial for reducing the intensity of clinical symptoms in children with croup, especially when moderate.

Are doctors using more preventive medication for cardiovascular disease? A Swedish cross-sectional study.

BACKGROUND: Despite decreasing mortality from cardiovascular disease (CVD), there are persistent inequities in mortality between socioeconomic groups. Primary preventative medications reduce mortality in CVD; thus, inequitable treatments will contribute to unequal outcomes. Physicians might contribute to inequality by prescribing preventative medication for CVD to themselves in a biased manner. AIM: To determine whether primary medications for preventing CVD were prescribed inequitably between physicians and non-physicians. DESIGN AND SETTING: This retrospective study retrieved registry data on prescribed medications for all physicians in Sweden aged 45-74 years, during 2013, and for reference non-physician individuals, matched by sex, age, residence, and level of education. The outcome was any medication for preventing CVD, received at least once during 2013. METHOD: Age and the sex-specific prevalence of myocardial infarction (MI) among physicians and non-physicians were used as a proxy for the need for medication. Thereafter, to limit the analysis to preventative medication, we excluded individuals that were diagnosed with CVD or diabetes. To analyse differences in medication usage between physicians and matched non-physicians, we estimated odds ratios (ORs) with conditional logistic regression and adjusted for need and household income. RESULTS: MI prevalences were 5.7% for men and 2.3% for women, among physicians, and 5.4% for men and 1.8% for women, among non-physicians. We included 25,105 physicians and 44,366 non-physicians. The OR for physicians receiving any CVD preventative medication, compared to non-physicians, was 1.65 (95% confidence interval 1.59-1.72). CONCLUSION: We found an inequity in prescribed preventative CVD medications, which favoured physicians over non-physicians.

KEYPOINTSGroups with low socioeconomic status have lower rates of using medication that prevents cardiovascular disease, compared to groups with high socioeconomic status.Physicians are responsible for prescribing all medicines to prevent cardiovascular disease; thus, biased prescriptions could have effects on the equality of care in the population.Compared to individuals with equivalent education, physicians had higher rates of using medication that prevents cardiovascular disease.This study highlights the need for systematic population-based evaluation of CVD risk in order to promote equitable CVD outcomes.

DeepBreath-automated detection of respiratory pathology from lung auscultation in 572 pediatric outpatients across 5 countries.

The interpretation of lung auscultation is highly subjective and relies on non-specific nomenclature. Computer-aided analysis has the potential to better standardize and automate evaluation. We used 35.9 hours of auscultation audio from 572 pediatric outpatients to develop DeepBreath : a deep learning model identifying the audible signatures of acute respiratory illness in children. It comprises a convolutional neural network followed by a logistic regression classifier, aggregating estimates on recordings from eight thoracic sites into a single prediction at the patient-level. Patients were either healthy controls (29%) or had one of three acute respiratory illnesses (71%) including pneumonia, wheezing disorders (bronchitis/asthma), and bronchiolitis). To ensure objective estimates on model generalisability, DeepBreath is trained on patients from two countries (Switzerland, Brazil), and results are reported on an internal 5-fold cross-validation as well as externally validated (extval) on three other countries (Senegal, Cameroon, Morocco). DeepBreath differentiated healthy and pathological breathing with an Area Under the Receiver-Operator Characteristic (AUROC) of 0.93 (standard deviation [SD] ± 0.01 on internal validation). Similarly promising results were obtained for pneumonia (AUROC 0.75 ± 0.10), wheezing disorders (AUROC 0.91 ± 0.03), and bronchiolitis (AUROC 0.94 ± 0.02). Extval AUROCs were 0.89, 0.74, 0.74 and 0.87 respectively. All either matched or were significant improvements on a clinical baseline model using age and respiratory rate. Temporal attention showed clear alignment between model prediction and independently annotated respiratory cycles, providing evidence that DeepBreath extracts physiologically meaningful representations. DeepBreath provides a framework for interpretable deep learning to identify the objective audio signatures of respiratory pathology.

Deep learning diagnostic and severity-stratification for interstitial lung diseases and chronic obstructive pulmonary disease in digital lung auscultations and ultrasonography: clinical protocol for an observational case-control study.

BACKGROUND: Interstitial lung diseases (ILD), such as idiopathic pulmonary fibrosis (IPF) and non-specific interstitial pneumonia (NSIP), and chronic obstructive pulmonary disease (COPD) are severe, progressive pulmonary disorders with a poor prognosis. Prompt and accurate diagnosis is important to enable patients to receive appropriate care at the earliest possible stage to delay disease progression and prolong survival. Artificial intelligence-assisted lung auscultation and ultrasound (LUS) could constitute an alternative to conventional, subjective, operator-related methods for the accurate and earlier diagnosis of these diseases. This protocol describes the standardised collection of digitally-acquired lung sounds and LUS images of adult outpatients with IPF, NSIP or COPD and a deep learning diagnostic and severity-stratification approach. METHODS: A total of 120 consecutive patients (≥ 18 years) meeting international criteria for IPF, NSIP or COPD and 40 age-matched controls will be recruited in a Swiss pulmonology outpatient clinic, starting from August 2022. At inclusion, demographic and clinical data will be collected. Lung auscultation will be recorded with a digital stethoscope at 10 thoracic sites in each patient and LUS images using a standard point-of-care device will be acquired at the same sites. A deep learning algorithm (DeepBreath) using convolutional neural networks, long short-term memory models, and transformer architectures will be trained on these audio recordings and LUS images to derive an automated diagnostic tool. The primary outcome is the diagnosis of ILD versus control subjects or COPD. Secondary outcomes are the clinical, functional and radiological characteristics of IPF, NSIP and COPD diagnosis. Quality of life will be measured with dedicated questionnaires. Based on previous work to distinguish normal and pathological lung sounds, we estimate to achieve convergence with an area under the receiver operating characteristic curve of > 80% using 40 patients in each category, yielding a sample size calculation of 80 ILD (40 IPF, 40 NSIP), 40 COPD, and 40 controls. DISCUSSION: This approach has a broad potential to better guide care management by exploring the synergistic value of several point-of-care-tests for the automated detection and differential diagnosis of ILD and COPD and to estimate severity. Trial registration Registration: August 8, 2022. CLINICALTRIALS: gov Identifier: NCT05318599.

Correction: Suppan et al. Impact of Two Resuscitation Sequences on Alveolar Ventilation during the First Minute of Simulated Pediatric Cardiac Arrest: Randomized Cross-Over Trial. Healthcare 2022, 10, 2451.

There was an error in the original publication [...].

Effectiveness of a Mobile App (PIMPmyHospital) in Reducing Therapeutic Turnaround Times in an Emergency Department: Protocol for a Pre- and Posttest Study.

BACKGROUND: Delays in reviewing issued laboratory results in emergency departments (EDs) can adversely affect efficiency and quality of care. One opportunity to improve therapeutic turnaround time could be to provide real-time access to laboratory results on mobile devices available to every caregiver. We developed a mobile app named "Patients In My Pocket in my Hospital" (PIMPmyHospital) to help ED caregivers automatically obtain and share relevant information about the patients they care for including laboratory results. OBJECTIVE: This pre- and posttest study aims to explore whether the implementation of the PIMPmyHospital app impacts the timeliness with which ED physicians and nurses remotely access laboratory results while actively working in their real-world environment, including ED length of stay, technology acceptance and usability among users, and how specific in-app alerts impact on its effectiveness. METHODS: This single-center study of nonequivalent pre- and posttest comparison group design will be conducted before and after the implementation of the app in a tertiary pediatric ED in Switzerland. The retrospective period will cover the previous 12 months, and the prospective period will cover the following 6 months. Participants will be postgraduate residents pursuing a ≤6-year residency in pediatrics, pediatric emergency medicine fellows, and registered nurses from the pediatric ED. The primary outcome will be the mean elapsed time in minutes from delivery of laboratory results to caregivers' consideration by accessing them either through the hospital's electronic medical records or through the app before and after the implementation of the app, respectively. As secondary outcomes, participants will be queried about the acceptance and usability of the app using the Unified Theory of Acceptance and Use of Technology model and the System Usability Scale. ED length of stay will be compared before and after the implementation of the app for patients with laboratory results. The impact of specific alerts on the app, such as a flashing icon or sound for reported pathological values, will be reported. RESULTS: Retrospective data collection gathered from the institutional data set will span a 12-month period from October 2021 to October 2022, while the 6-month prospective collection will begin with the implementation of the app in November 2022 and is expected to cease at the end of April 2023. We expect the results of the study to be published in a peer-reviewed journal in late 2023. CONCLUSIONS: This study will show the potential reach, effectiveness, acceptance, and use of the PIMPmyHospital app among ED caregivers. The findings of this study will serve as the basis for future research on the app and any further development to improve its effectiveness. Trial Registration: ClinicalTrials.gov NCT05557331; https://clinicaltrials.gov/ct2/show/NCT05557331. TRIAL REGISTRATION: ClinicalTrials.gov NCT05557331; https://clinicaltrials.gov/ct2/show/NCT05557331. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/43695.

Impairment of quality of life due to COVID-19-induced long-term olfactory dysfunction.

Introduction: Olfactory dysfunction is one of many long-lasting symptoms associated with COVID-19, estimated to affect approximately 60% of individuals and often lasting several months after infection. The associated daily life problems can cause a decreased quality of life. Methods: Here, we assessed the association between perceived quality of life and both qualitative and quantitative olfactory function (distorted and weakened sense of smell, respectively) in 58 individuals who had undergone confirmed SARS-CoV-2 infection and who complained about olfactory dysfunction. Results: Participants with large quantitative olfactory dysfunction experienced a greater reduction in their quality of life. Moreover, our participants had a high prevalence of qualitative olfactory dysfunction (81%) with a significant correlation between qualitative olfactory dysfunction and daily life impairment. Strong drivers of low quality of life assessments were lack of enjoyment of food as well as worries related to coping with long-term dysfunctions. Discussion: These results stress the clinical importance of assessing qualitative olfactory dysfunction and the need to develop relevant interventions. Given the poor self-rated quality of life observed, healthcare systems should consider developing support structures, dietary advice, and guidelines adapted to individuals experiencing qualitative olfactory dysfunction.

Functional re-organization of hippocampal-cortical gradients during naturalistic memory processes.

The functional organization of the hippocampus mirrors that of the cortex, changing smoothly along connectivity gradients and abruptly at inter-areal boundaries. Hippocampal-dependent cognitive processes require flexible integration of these hippocampal gradients into functionally related cortical networks. To understand the cognitive relevance of this functional embedding, we acquired fMRI data while participants viewed brief news clips, either containing or lacking recently familiarized cues. Participants were 188 healthy mid-life adults and 31 adults with mild cognitive impairment (MCI) or Alzheimer's disease (AD). We employed a recently developed technique - connectivity gradientography - to study gradually changing patterns of voxel to whole brain functional connectivity and their sudden transitions. We observed that functional connectivity gradients of the anterior hippocampus map onto connectivity gradients across the default mode network during these naturalistic stimuli. The presence of familiar cues in the news clips accentuates a stepwise transition across the boundary from the anterior to the posterior hippocampus. This functional transition is shifted in the posterior direction in the left hippocampus of individuals with MCI or AD. These findings shed new light on the functional integration of hippocampal connectivity gradients into large-scale cortical networks, how these adapt with memory context and how these change in the presence of neurodegenerative disease.