Faculty Bibliography

Olfaction, the sense of smell, is characterized by a notable age-dependency such that aging individuals are more likely to have poor olfactory abilities. These impairments are considered to be mostly irreversible and as having potentially profound effects on quality of life and food behavior, as well as constituting warning signs of mortality, cognitive dysfunction, and dementia. Here, we review the current state of research on aging and olfaction, focusing on five topics which we regard to be of particular relevance for the field: nutrition and health, cognition and dementia, mortality, environment and genetics, and training-based enhancement. Under each of these headlines, we provide a state-of-the-art overview and discuss gaps in our knowledge which might be filled by further research. Understanding how olfactory abilities are diminished in aging, and how they may be alleviated or recovered, involves a set of challenging tasks for researchers in the years to come.

Trait impulsivity is a multifaceted personality characteristic that contributes to maladaptive life outcomes. Although a growing body of neuroimaging studies have investigated the structural correlates of trait impulsivity, the findings remain highly inconsistent and heterogeneous. Herein, we performed a systematic review to depict an integrated delineation of gray matter (GM) substrates of trait impulsivity and a meta-analysis to examine concurrence across previous whole-brain voxel-based morphometry studies. The systematic review summarized the diverse findings in GM morphometry in the past literature, and the quantitative meta-analysis revealed impulsivity-related volumetric GM alterations in prefrontal, temporal, and parietal cortices. In addition, we identified the modulatory effects of age and gender in impulsivity-GM volume associations. The present study advances understanding of brain GM morphometry features underlying trait impulsivity. The findings may have practical implications in the clinical diagnosis of and intervention for impulsivity-related disorders.

Cerebrovascular reactivity (CVR) is of great significance for the treatment and prevention of cerebrovascular diseases. CVR can be mapped using the blood oxygenation level-dependent (BOLD) signal of fMRI. Breath holding (BH) is a reliable method to produce the desired increase in arterial CO₂, while its application in clinical research is limited due to subject's compliance and variability. BH task with variable respiratory rates could allow more flexibility in clinical populations. In this study, 50 healthy volunteers were scanned for end-inspiration BH tasks with three different respiration rates. For the three respiratory rates BH tasks, the CVR was estimated based on the BOLD signal and general linear model (GLM) separately. Specifically, the extra time delay was considered for the hemodynamic response function, and the optimal delay was estimated for each voxel. To measure CVR in grey matter, BOLD signals of end-inspiration BH were used as regressors in general linear models to quantify their impact on CVR. This was performed for regions and voxels. Systematic differences were observed between the three end-inspiratory breathing rates. The greatest increase in activation intensity was found in fast breathing followed by self-paced and slow breathing. We conclude that the BH task of variable respiratory rates allows for CVR measurement, making breath-holding challenges more flexible and appropriate for routine practice.

BACKGROUND AND AIM/OBJECTIVE:There are only a few reports of non-Helicobacter pylori Helicobacter (NHPH) gastritis in Japanese patients. We aimed to examine its prevalence, clinical features, and esophagogastroduodenoscopy (EGD) findings based on 50 patients encountered in one facility. MATERIALS AND METHODS/METHODS:Subjects were all patients who had undergone gastric mucosal biopsy endoscopically at Kenwakai Hospital for approximately 10 years. NHPH infection was diagnosed by microscopic findings of Giemsa staining performed on all specimens. PCR analysis of urease genes was performed to detect and identify NHPH, when informed consent was obtained. Helicobacter pylori-diagnostic tests were also performed. NHPH-infected patients were questioned about symptoms and animal contact. RESULTS:NHPH gastritis was found in 50 of 3847 patients (1.30%). The percentage increased to 3.35% (30 of 896 patients) in the latter 2 years and 4 months with increasing recognition of its characteristic endoscopic findings by endoscopists. PCR analysis, performed in 30 patients, detected NHPH in 28 patients: 26 as Helicobacter suis and 2 as Helicobacter heilmanii/Helicobacter ailurogastricus. Helicobacter pylori-diagnostic tests were almost negative. However, anti-H. pylori antibody showed high-negative titer (3.0-9.9 U/ml) in 12. Of 50 patients (consisting of 49 men and 1 woman), almost all were asymptomatic, and 25 were keeping pets. Regarding EGD findings, in all 50 patients, "crack-like mucosa" and/or nodular gastritis was noted in gastric antrum, and regular arrangement of collecting venules (RAC) was noted in gastric corpus. None of the patients infected with NHPH were co-infected with H. pylori. CONCLUSIONS:The prevalence was finally estimated to be approximately 3.35%. Helicobacter suis was the most common NHPH species. "Crack-like mucosa" and/or nodular gastritis in gastric antrum, RAC in gastric corpus, and H. pylori-negativity by H. pylori-diagnostic tests especially containing a high-negative titer of anti-H. pylori antibody may indicate NHPH infection.

Interval timing, the ability to encode and retrieve the memory of intervals from seconds to minutes, guides fundamental animal behaviors across the phylogenetic tree. In Pavlovian fear conditioning, an initially neutral stimulus (conditioned stimulus, CS) predicts the arrival of an aversive unconditioned stimulus (US, generally a mild foot-shock) at a fixed time interval. Although some studies showed that temporal relations between CS and US events are learned from the outset of conditioning, the question of the memory of time and its underlying neural network in fear conditioning is still poorly understood. The aim of the present study was to investigate the role of the dorsal striatum in timing intervals in odor fear conditioning in male rats. To assess the animal's interval timing ability in this paradigm, we used the respiratory frequency. This enabled us to detect the emergence of temporal patterns related to the odor-shock time interval from the early stage of learning, confirming that rats are able to encode the odor-shock time interval after few training trials. We carried out reversible inactivation of the dorsal striatum before the acquisition session and before a shift in the learned time interval, and measured the effects of this treatment on the temporal pattern of the respiratory rate. In addition, using intracerebral microdialysis, we monitored extracellular dopamine level in the dorsal striatum throughout odor-shock conditioning and in response to a shift of the odor-shock time interval. Contrary to our initial predictions based on the existing literature on interval timing, we found evidence suggesting that transient inactivation of the dorsal striatum may favor a more precocious buildup of the respiratory frequency's temporal pattern during the odor-shock interval in a manner that reflected the duration of the interval. Our data further suggest that the conditioning and the learning of a novel time interval were associated with a decrease in dopamine level in the dorsal striatum, but not in the nucleus accumbens. These findings prompt a reassessment of the role of the striatum and striatal dopamine in interval timing, at least when considering Pavlovian aversive conditioning.

We rapidly classify odors as pleasant or aversive, but the brain circuits underlying how odors motivate approach and avoidance responses are largely unknown. New research describes a direct path from the olfactory bulb to ventral striatum driving odor-mediated reward.

CLINICAL TRIAL REGISTRATION/UNASSIGNED:ClinicalTrials.gov identifier: NCT03583541.

LAY ABSTRACT/UNASSIGNED:Smoking prevention, especially in pregnancy planning, may decrease autism spectrum disorder risk in offspring.

Individuals with Autism Spectrum Disorder (ASD) without intellectual disability (ID) represent approximately two-thirds of the ASD population. Here we focused on prospective research assessing different areas of functioning of children with ASD, without ID, until adolescence. Based on a pre-registered protocol (PROSPERO CRD42020189029), a systematic review of prospective studies (published between 01.01.2010 and 01.01.2020) was conducted. Twenty-eight studies met eligibility criteria. Findings indicated that ASD diagnosis and the Intelligence Quotient were highly stable over time across studies. Executive Functioning, Theory of Mind and Central Coherence processes tended to improve, although deficits remained when compared to typically developed controls. Adaptive difficulties and psychiatric comorbidity were relatively stable over time. We discuss potential implications of the findings for clinicians and educators and suggest recommendations for future research.

OBJECTIVE:This study aimed to describe informant discrepancies between mother and father reports of child vulnerability in youth with spina bifida (SB) and examine variables that were associated with these discrepancies. METHODS:Ninety-two parent dyads, with a child with SB (ages 8-15 years), were recruited as a part of a longitudinal study. Mothers and fathers completed questionnaires assessing parental perception of child vulnerability (PPCV), as well as medical and demographic information, behavioral aspects of the couple relationship, parenting stress, mental health of the parent, and child behavioral adjustment. The degree to which there was a parenting alliance was assessed with observational data. Mother-father discrepancies were calculated at the item level. RESULTS:Findings revealed that greater father mental health symptoms, parenting stress, and child behavior problems were associated with "father high and mother low" discrepancies in PPCV. There were also lower scores on observed parenting alliance when there were higher rates of "father high and mother low" discrepancies in PPCV. CONCLUSIONS:For families of youth with SB, discrepancies in PPCV where fathers perceive high vulnerability and mothers perceive low vulnerability may be a "red flag" for the presence of other parental and child adjustment difficulties. Findings are discussed in terms of the Attribution Bias Context Model and underscore the importance of including fathers in research on families who have children with chronic health conditions.