Metabolic Dynamics in the Prefrontal Cortex during a Working Memory Task in Young Adult Smokers.

INTRODUCTION: Cigarette smoking is known to modulate brain metabolism and brain function. How the dynamics of these metabolic alterations influence the active performance of higher order cognitive tasks in smokers, compared to non-smokers, is still unclear. The present exploratory study sought to examine the impact of smoking on the "complete" metabolic profile while the participants performed a working memory (N-back) task. METHODS: The study sample consisted of 40 young male healthy participants (smokers [n = 20] and non-smokers [n = 20]). Functional magnetic resonance spectroscopy data were acquired using a 3 T whole-body MR system. Data analysis was performed using Java-based Magnetic Resonance User Interface software, and metabolite ratios with respect to creatine (Cr) were calculated. RESULTS: On a behavioural level, smokers showed worse performance (measured by d') than non-smokers. However, we observed significant differences in the metabolite concentrations in smokers compared to non-smokers, which also changed over the course of the N-back task. A significant effect of the group was observed with smokers showing lower glutamate/Cr (Glx/Cr) and choline/Cr (Cho/Cr) ratios than non-smokers. Further, N-acetyl aspartate (NAA/Cr) and Cho/Cr ratios were significantly different during the rest and the task conditions. In addition, our results demonstrated the metabolite interactions (NAA and Cho, Glx and myo-inositol [mI], and Cho and mI). CONCLUSION: Further studies are necessary to shed more light on the association between smoking behaviours and metabolic alterations. However, our preliminary findings would assist in this future research to have a complete understanding of the metabolite interactions not only in smoking but also in addiction research.

Human body odor increases familiarity for faces during encoding-retrieval task.

Odors can increase memory performance when presented as context during both encoding and retrieval phases. Since information from different sensory modalities is integrated into a unified conceptual knowledge, we hypothesize that the social information from body odors and faces would be integrated during encoding. The integration of such social information would enhance retrieval more so than when the encoding occurs in the context of common odors. To examine this hypothesis and to further explore the underlying neural correlates of this behavior, we have conducted a functional magnetic resonance imaging study in which participants performed an encoding-retrieval memory task for faces during the presentation of common odor, body odor or clean air. At the behavioral level, results show that participants were less biased and faster in recognizing faces when presented in concomitance with the body odor compared to the common odor. At the neural level, the encoding of faces in the body odor condition, compared to common odor and clean air conditions, showed greater activation in areas related to associative memory (dorsolateral prefrontal cortex), odor perception and multisensory integration (orbitofrontal cortex). These results suggest that face and body odor information were integrated and as a result, participants were faster in recognizing previously presented material.

More Than Smell-COVID-19 Is Associated With Severe Impairment of Smell, Taste, and Chemesthesis.

Recent anecdotal and scientific reports have provided evidence of a link between COVID-19 and chemosensory impairments, such as anosmia. However, these reports have downplayed or failed to distinguish potential effects on taste, ignored chemesthesis, and generally lacked quantitative measurements. Here, we report the development, implementation, and initial results of a multilingual, international questionnaire to assess self-reported quantity and quality of perception in 3 distinct chemosensory modalities (smell, taste, and chemesthesis) before and during COVID-19. In the first 11 days after questionnaire launch, 4039 participants (2913 women, 1118 men, and 8 others, aged 19-79) reported a COVID-19 diagnosis either via laboratory tests or clinical assessment. Importantly, smell, taste, and chemesthetic function were each significantly reduced compared to their status before the disease. Difference scores (maximum possible change ±100) revealed a mean reduction of smell (-79.7 ± 28.7, mean ± standard deviation), taste (-69.0 ± 32.6), and chemesthetic (-37.3 ± 36.2) function during COVID-19. Qualitative changes in olfactory ability (parosmia and phantosmia) were relatively rare and correlated with smell loss. Importantly, perceived nasal obstruction did not account for smell loss. Furthermore, chemosensory impairments were similar between participants in the laboratory test and clinical assessment groups. These results show that COVID-19-associated chemosensory impairment is not limited to smell but also affects taste and chemesthesis. The multimodal impact of COVID-19 and the lack of perceived nasal obstruction suggest that severe acute respiratory syndrome coronavirus strain 2 (SARS-CoV-2) infection may disrupt sensory-neural mechanisms.

The microbiome of the upper respiratory tract in health and disease.

The human upper respiratory tract (URT) offers a variety of niches for microbial colonization. Local microbial communities are shaped by the different characteristics of the specific location within the URT, but also by the interaction with both external and intrinsic factors, such as ageing, diseases, immune responses, olfactory function, and lifestyle habits such as smoking. We summarize here the current knowledge about the URT microbiome in health and disease, discuss methodological issues, and consider the potential of the nasal microbiome to be used for medical diagnostics and as a target for therapy.

When to collect resting-state data: The influence of odor on post-task resting-state connectivity.

The human brain networks at rest represent spontaneous activity that is highly correlated between different brain regions. Previous studies have shown that these resting-state networks are flexible and dynamic, and they can be affected by performance of different types of tasks. Moreover, it has been suggested that the re-activation of a task-related brain network during rest promotes learning and improves the expertise on that task. However, it is still unclear whether the presence of different sensory information in the on-task state affects functional connectivity in subsequent resting-state fMRI even though the perception of the sensory information did not induce significant behavioral effects. To clarify this issue, we compared pre- and post-task resting-state fMRI of two groups of participants performing the same task either with an odor context (ODOR group) or without an odor context (AIR group). Seed-based functional connectivity analyses were performed with orbitofrontal cortex, piriform cortex and working-memory core network as seeds. The results showed that an odor context presented during an encoding task induced significant changes in the functional connectivity only within the olfactory network of the post-task resting-state compared to the same post-task situation without previous odor context. No significant difference in functional connectivity were found for the working-memory core network. This evidence emphasizes how the sensory context, in which a task is performed, is relevant for understanding the observed changes of functional connectivity during rest.

Influence of 4-week multi-strain probiotic administration on resting-state functional connectivity in healthy volunteers.

PURPOSE: Experimental investigations in rodents have contributed significantly to our current understanding of the potential importance of the gut microbiome and brain interactions for neurotransmitter expression, neurodevelopment, and behaviour. However, clinical evidence to support such interactions is still scarce. The present study used a double-blind, randomized, pre- and post-intervention assessment design to investigate the effects of a 4-week multi-strain probiotic administration on whole-brain functional and structural connectivity in healthy volunteers. METHODS: Forty-five healthy volunteers were recruited for this study and were divided equally into three groups (PRP: probiotic, PLP: placebo, and CON: control). All the participants underwent resting-state functional MRI and diffusion MRI brain scans twice during the course of study, at the beginning (time point 1) and after 4 weeks (time point 2). MRI data were acquired using a 3T whole-body MR system (Magnetom Skyra, Siemens, Germany). RESULTS: Functional connectivity (FC) changes were observed in the default mode network (DMN), salience network (SN), and middle and superior frontal gyrus network (MFGN) in the PRP group as compared to the PLP and CON groups. PRP group showed a significant decrease in FC in MFGN (in frontal pole and frontal medial cortex) and in DMN (in frontal lobe) as compared to CON and PLP groups, respectively. Further, significant increase in FC in SN (in cingulate gyrus and precuneus cortex) was also observed in PRP group as compared to CON group. The significance threshold was set to p < 0.05 FWE corrected. No significant structural differences were observed between the three groups. CONCLUSIONS: This work provides new insights into the role of a multi-strain probiotic administration in modulating the behaviour, which is reflected as changes in the FC in healthy volunteers. This study motivates future investigations into the role of probiotics in context of major depression and stress disorders.

Severity of olfactory deficits is reflected in functional brain networks-An fMRI study.

Even though deficits in olfactory function affect a considerable part of the population, the neuronal basis of olfactory deficits remains scarcely investigated. To achieve a better understanding of how smell loss affects neural activation patterns and functional networks, we set out to investigate patients with olfactory dysfunction using functional magnetic resonance imaging (fMRI) and olfactory stimulation. We used patients' scores on a standardized olfactory test as continuous measure of olfactory function. 48 patients (mean olfactory threshold discrimination identification (TDI) score = 16.33, SD = 6.4, range 6 - 28.5) were investigated. Overall, patients showed piriform cortex activation during odor stimulation compared to pure sniffing. Group independent component analysis indicated that the recruitment of three networks during odor stimulation was correlated with olfactory function: a sensory processing network (including regions such as insula, thalamus and piriform cortex), a cerebellar network and an occipital network. Interestingly, recruitment of these networks during pure sniffing was related to olfactory function as well. Our results support previous findings that sniffing alone can activate olfactory regions. Extending this, we found that the severity of olfactory deficits is related to the extent to which neural networks are recruited both during olfactory stimulation and pure sniffing. This indicates that olfactory deficits are not only reflected in changes in specific olfactory areas but also in the recruitment of occipital and cerebellar networks. These findings pave the way for future investigations on whether characteristics of these networks might be of use for the prediction of disease prognosis or of treatment success.

Temporal muscle thickness is an independent prognostic marker in melanoma patients with newly diagnosed brain metastases.

OBJECTIVES: The purpose of this study was to evaluate the prognostic relevance of temporal muscle thickness (TMT) in melanoma patients with newly diagnosed brain metastases. METHODS: TMT was retrospectively assessed in 146 melanoma patients with newly diagnosed brain metastases on cranial magnetic resonance images. Chart review was used to retrieve clinical parameters, including disease-specific graded prognostic assessment (DS-GPA) and survival times. RESULTS: Patients with a TMT > median showed a statistically significant increase in survival time (13 months) compared to patients with a TMT < median (5 months; p < 0.001; log rank test). A Cox regression model revealed that the risk of death was increased by 27.9% with every millimeter reduction in TMT. In the multivariate analysis, TMT (HR 0.724; 95% 0.642-0.816; < 0.001) and DS-GPA (HR 1.214; 95% CI 1.023-1.439; p = 0.026) showed a statistically significant correlation with overall survival. CONCLUSION: TMT is an independent predictor of survival in melanoma patients with brain metastases. This parameter may aid in patient selection for clinical trials or to the choice of different treatment options based on the determination of frail patient populations.

Modulation of resting-state network connectivity by verbal divergent thinking training.

A growing body of evidence suggests that creativity is associated with functional connectivity across widespread neural networks, including regions associated with executive processes and cognitive control, along with regions linked to the default mode network (DMN) of the brain. This study investigated whether a three-week verbal divergent thinking training modulates functional connectivity in networks that have been related to creativity. In a task-based functional imaging study (Fink et al., 2015), the employed creativity training was found to modulate brain activity in regions closely associated with semantic memory demands. Hence, the specific aim of this study was to assess whether the observed task-related brain changes relate to changes in functional connectivity patterns of the brain at rest, as assessed by independent component analysis. The participants were tested at three time points with an inter-test interval of four weeks each, and randomly assigned to two groups which received the verbal creativity training time-delayed. Findings revealed that successful training of verbal creativity was mirrored by functional connectivity changes in the DMN, sensorimotor and auditory network, and the attention network. These rather global changes in resting-state functional connectivity supplement the findings of task-based fMRI, where changes in more task specific brain regions were found.

Investigating Sex-Specific Characteristics of Nicotine Addiction Using Metabolic and Structural Magnetic Resonance Imaging.

Nicotine addiction is known to modulate neurotransmission and alter the brain structure. The detrimental effect of nicotine is more prominent in females as compared to males. This study sought to examine the sex-specific influence of nicotine addiction on gamma amino butyric acid (GABA) and the white matter (WM) microstructure. Sixty healthy subjects (smokers/non-smokers) underwent structural and metabolic magnetic resonance imaging scans. Results showed alterations in WM integrity (measured as changes in fractional anisotropy [FA] and GABA in smokers versus non-smokers and females versus males. No overall significant smoking and sex-specific interactions were observed in this study. However, on comparing female smokers with female non-smokers, significantly higher GABA and FA values were observed in female smokers. However, GABA and FA values did not differ significantly when male smokers were compared against male non-smokers. Our results provide a further rationale to investigate the impact of nicotine on central GABAergic function and WM integrity, in particular due to the potential risk for females to experience depressive/anxiety symptoms during smoking cessation.

Anosmia-A Clinical Review.

Anosmia and hyposmia, the inability or decreased ability to smell, is estimated to afflict 3-20% of the population. Risk of olfactory dysfunction increases with old age and may also result from chronic sinonasal diseases, severe head trauma, and upper respiratory infections, or neurodegenerative diseases. These disorders impair the ability to sense warning odors in foods and the environment, as well as hinder the quality of life related to social interactions, eating, and feelings of well-being. This article reports and extends on a clinical update commencing at the 2016 Association for Chemoreception Sciences annual meeting. Included were reports from: a patient perspective on losing the sense of smell with information on Fifth Sense, a nonprofit advocacy organization for patients with olfactory disorders; an otolaryngologist's review of clinical evaluation, diagnosis, and management/treatment of anosmia; and researchers' review of recent advances in potential anosmia treatments from fundamental science, in animal, cellular, or genetic models. As limited evidence-based treatments exist for anosmia, dissemination of information on anosmia-related health risks is needed. This could include feasible and useful screening measures for olfactory dysfunction, appropriate clinical evaluation, and patient counseling to avoid harm as well as manage health and quality of life with anosmia.

Survival prediction using temporal muscle thickness measurements on cranial magnetic resonance images in patients with newly diagnosed brain metastases.

OBJECTIVES: To evaluate the prognostic relevance of temporal muscle thickness (TMT) in brain metastasis patients. METHODS: We retrospectively analysed TMT on magnetic resonance (MR) images at diagnosis of brain metastasis in two independent cohorts of 188 breast cancer (BC) and 247 non-small cell lung cancer (NSCLC) patients (overall: 435 patients). RESULTS: Survival analysis using a Cox regression model showed a reduced risk of death by 19% with every additional millimetre of baseline TMT in the BC cohort and by 24% in the NSCLC cohort. Multivariate analysis included TMT and diagnosis-specific graded prognostic assessment (DS-GPA) as covariates in the BC cohort (TMT: HR 0.791/CI [0.703-0.889]/p < 0.001; DS-GPA: HR 1.433/CI [1.160-1.771]/p = 0.001), and TMT, gender and DS-GPA in the NSCLC cohort (TMT: HR 0.710/CI [0.646-0.780]/p < 0.001; gender: HR 0.516/CI [0.387-0.687]/p < 0.001; DS-GPA: HR 1.205/CI [1.018-1.426]/p = 0.030). CONCLUSION: TMT is easily and reproducibly assessable on routine MR images and is an independent predictor of survival in patients with newly diagnosed brain metastasis from BC and NSCLC. TMT may help to better define frail patient populations and thus facilitate patient selection for therapeutic measures or clinical trials. Further prospective studies are needed to correlate TMT with other clinical frailty parameters of patients. KEY POINTS: • TMT has an independent prognostic relevance in brain metastasis patients. • It is an easily and reproducibly parameter assessable on routine cranial MRI. • This parameter may aid in patient selection and stratification in clinical trials. • TMT may serve as surrogate marker for sarcopenia.

Disgust-Related Olfactory Processing: The Role of Gender and Trait Disgust.

For the rejection of disgusting and potentially health-threatening food, the sense of smell plays a critical role. We conducted two experiments in order to investigate the role of gender and trait disgust (the temporally stable tendency to experience disgust across different situations) on disgust-related olfactory processing. A total of 40 men and women (Study 1), as well as a group of women divided according to high versus low trait disgust (Study 2, n = 59), were compared with regard to their odor thresholds for carbon disulfide (which smells like spoiled food) and a control stimulus ( n-butanol). The stimuli were rated for experienced arousal, negative valence, and familiarity. In addition, all participants underwent the "Sniffin' Sticks" battery assessing general olfactory performance. We found that women had a lower carbon disulfide threshold and rated this odorant as more unpleasant than men. Trait disgust was neither associated with the detection of the odorant signaling spoilage, nor with general olfactory function. The latter finding questions the role of this personality trait for olfactory-driven food-rejection responses, at least for normosmic individuals.

Assessment of Olfactory Memory in Olfactory Dysfunction.

To assess all clinically relevant components of olfactory perception, examinations for olfactory sensitivity, discrimination, and identification are performed. Besides the standard perceptual test battery, episodic olfactory memory might offer additional information about olfactory abilities relative to these standard clinical tests. As both olfactory deficits and memory deficits are early symptoms in neurodegenerative disorders, olfactory memory may be of particular interest. However, to date little is known about episodic olfactory memory performance in patients with decreased olfactory function. This study includes the investigation of olfactory memory performance in 14 hyposmic patients (8 female, mean age 52.6 years) completing two episodic odor memory tests (Sniffin' Test of Odor Memory and Odor Memory Test). To control for a general impairment in memory function, a verbal and a figural memory test were carried out. A regression model with multiple predictors was calculated for both odor memory tests separately. Odor identification was identified as the only significant predictor for both odor memory tasks. From our results, we conclude that currently available olfactory memory tests are highly influenced by odor identification abilities, implying the need for the development and validation of additional tests in this field which could serve as additional olfactory perception variables for clinical assessment.

Detecting cam-type deformities on plain radiographs: what is the optimal lateral view?

PURPOSE: Radial magnetic resonance imaging (MRI) is the most accurate diagnostic tool in assessing cam-type femoroacetabular impingement. Plain radiographs, however, are useful for the initial diagnosis in the daily practice and there is still debate regarding the optimal lateral view. The purpose of this study was to investigate the reliability of detecting cam deformities using the frog-leg view or the 45° Dunn view by comparison with radial MRI. MATERIAL: 66 consecutive hips with plain radiographs (36 with AP and frog-leg views, 30 with AP and 45° Dunn views) and radial MRI were assessed. Alpha angle measurements were obtained both for radiographs and for radial MRI reformats by two investigators. Statistics included frequency analysis, bivariate linear correlation analyses, and cross-table analyses testing the sensitivity and specificity of the radiographic projections for detecting an alpha angle larger than 55°. RESULTS: The intra-class correlation revealed excellent agreement between the two raters [ICC = 0.959, CI (0.943; 0.972)]. 50% (33/66) had the maximum alpha angle in the superior-anterior aspect of the femoral head-neck junction. Cam deformity was found in 40/66 cases (61%) in radial MRI. Pearson correlation demonstrated that the 45° Dunn view was most accurate for the superior-anterior aspect (0.730, p < 0.05). The frog-leg view was best suited for the anterior aspect (0.703, p < 0.05). The sensitivity for detecting cam deformities in the 45° Dunn view was 84 vs 62% in the frog-leg view. CONCLUSION: The frog-leg lateral radiograph does not provide reliable measurements of the alpha angle. This study highlights the importance of the 45° Dunn view for early detection of femoroacetabular cam-type impingement.

Fetal diffusion tensor quantification of brainstem pathology in Chiari II malformation.

OBJECTIVES: This prenatal MRI study evaluated the potential of diffusion tensor imaging (DTI) metrics to identify changes in the midbrain of fetuses with Chiari II malformations compared to fetuses with mild ventriculomegaly, hydrocephalus and normal CNS development. METHODS: Fractional anisotropy (FA) and apparent diffusion coefficient (ADC) were calculated from a region of interest (ROI) in the midbrain of 46 fetuses with normal CNS, 15 with Chiari II malformations, eight with hydrocephalus and 12 with mild ventriculomegaly. Fetuses with different diagnoses were compared group-wise after age-matching. Axial T2W-FSE sequences and single-shot echo planar DTI sequences (16 non-collinear diffusion gradient-encoding directions, b-values of 0 and 700 s/mm(2), 1.5 Tesla) were evaluated retrospectively. RESULTS: In Chiari II malformations, FA was significantly higher than in age-matched fetuses with a normal CNS (p = .003), while ADC was not significantly different. No differences in DTI metrics between normal controls and fetuses with hydrocephalus or vetriculomegaly were detected. CONCLUSIONS: DTI can detect and quantify parenchymal alterations of the fetal midbrain in Chiari II malformations. Therefore, in cases of enlarged fetal ventricles, FA of the fetal midbrain may contribute to the differentiation between Chiari II malformation and other entities. KEY POINTS: • FA in the fetal midbrain is elevated in Chiari II malformations. • FA is not elevated in hydrocephalus and mild ventriculomegaly without Chiari II. • Measuring FA may help distinguish different causes for enlarged ventricles prenatally. • Elevated FA may aid in the diagnosis of open neural tube defects. • Elevated FA might contribute to stratification for prenatal surgery in Chiari II.

Disrupted developmental organization of the structural connectome in fetuses with corpus callosum agenesis.

Agenesis of the corpus callosum is a model disease for disrupted connectivity of the human brain, in which the pathological formation of interhemispheric fibers results in subtle to severe cognitive deficits. Postnatal studies suggest that the characteristic abnormal pathways in this pathology are compensatory structures that emerge via neural plasticity. We challenge this hypothesis and assume a globally different network organization of the structural interconnections already in the fetal acallosal brain. Twenty fetuses with isolated corpus callosum agenesis with or without associated malformations were enrolled and fiber connectivity among 90 brain regions was assessed using in utero diffusion tensor imaging and streamline tractography. Macroscopic scale connectomes were compared to 20 gestational age-matched normally developing fetuses with multiple granularity of network analysis. Gradually increasing connectivity strength and tract diffusion anisotropy during gestation were dominant in antero-posteriorly running paramedian and antero-laterally running aberrant pathways, and in short-range connections in the temporoparietal regions. In fetuses with associated abnormalities, more diffuse reduction of cortico-cortical and cortico-subcortical connectivity was observed than in cases with isolated callosal agenesis. The global organization of anatomical networks consisted of less segregated nodes in acallosal brains, and hubs of dense connectivity, such as the thalamus and cingulate cortex, showed reduced network centrality. Acallosal fetal brains show a globally altered connectivity network structure compared to normals. Besides the previously described Probst and sigmoid bundles, we revealed a prenatally differently organized macroconnectome, dominated by increased connectivity. These findings provide evidence that abnormal pathways are already present during at early stages of fetal brain development in the majority of cerebral white matter.

Stress matters! Psychophysiological and emotional loadings of pregnant women undergoing fetal magnetic resonance imaging.

BACKGROUND: While the application of fetal MRI in high-risk pregnant women is steadily rising, little is known about the psychological consequences of this procedure. The aim of the present study was to investigate emotional and psychophysiological reactions of females undergoing fetal MRI. METHODS: Sixty women (17-44 ys), assigned for fetal MRI, were included. Affective state was assessed by standardized measures of anxiety, emotional states and depressive symptoms. Stress coping strategies were assessed using a self-report questionnaire. Stress responses were determined using skin conductance levels (SCL) during fetal MRI as well as measurement of salivary cortisol levels immediately before and after fetal MRI. RESULTS: Analysis of fast and slow physiological stress measures revealed significant differences between women with and without a supporting person accompanying them to the examination. For SCLs, lower levels of stress during MRI emerged in accompanied women. Women with well-marked stress-coping-strategies experienced lower levels of stress during the examination. Although fast and slow stress measures before and after MRI did not show significant correlations, a significant difference of SCLs pre and post examination was clearly detectable, as well as a trend of decreased cortisol levels for both time points. CONCLUSIONS: The results imply that the elevation of SCLs is an accurate instrument to assess fast stress alterations in patients during fetal MRI. Stress coping strategies and whether women are accompanied or not play an important role in the experience of anxiety and depressive symptoms. These factors should be considered especially in patients with high-risk-pregnancies to improve patient care.