Primary sensory cortices have been demonstrated to process sensory input from non-preferred sensory modalities, e.g., primary visual cortex reacting to auditory stimulation, bringing their presumed sensory specificity into question. Whether this reflects processing of the non-preferred stimulus per se or originates from cross-modal associations is debated. Visual/auditory objects typically have strong reciprocal associations; hence, it is difficult to address this question in these modalities. Here, we dissociate between the two competing hypotheses of whether this form of activation in primary cortices is caused by unisensory processing or cross-modal associations by turning to the olfactory system where cross-modal associations are generally weaker. Using unisensory visual and auditory objects with odor associations ranging from none to strong, we show that the posterior piriform cortex, an area known to process odor objects, is activated by both sounds and pictures of objects. Critically, this activation is independent of the objects' odor associations, thereby demonstrating that the activity is not due to cross-modal associations. Using a Floyd–Warshall algorithm, we further show that the amygdala mediate condition-relevant information between the posterior piriform cortex and both the auditory and visual object-oriented cortices. Importantly, we replicate past findings of clear crossmodal processing in the visual and auditory systems. Our study demonstrates processing of non-olfactory input in olfactory cortices that is independent of cross-modal associations and contributes to a more nuanced view of modality specificity in olfactory, auditory, and visual cortices.

BACKGROUND: Although most patients with post-traumatic olfactory dysfunction (PTOD) undergo MRI, there is no consensus about its diagnostic or prognostic value.The aims were: 1) to classify the extent of post-traumatic neurodegeneration; 2) todetermine its relationship with chemosensory dysfunction (smell, taste, trigeminal); and 3) to establish whether MRI can predict olfactory improvement. METHODOLOGY: We conducted a retrospective cohort study based on a series of 56 patients with PTOD. All patients underwent validated psychophysical tests of their smell, taste, and trigeminal functions, otorhinolaryngologic evaluation, and MRI. An experiencedradiologist blinded to patient data evaluated 40 chemosensory-relevant brain regions according to a four-point scale (0=no lesion to 3=large lesion). Follow up data after 4 years (on average) were available in 46 patients. RESULTS:The cluster analysis showed 4 brain lesion patterns that differed in lesion localization and severity. They are associatedwith diagnostic categories: anosmia, hyposmia and normosmia. Two clusters were highly specific for anosmia (100% specificity)and could accurately predict this condition (100% positive predictive value). No clusters were associated with trigeminal or tastedysfunction. Regarding improvement, 72.7% of patients in the cluster with mild lesions experienced subjective and measurable olfactory improvement whereas this was only the case in 21.7-37.5% of patients with larger lesions. The odds of subjective smellimprovement were 5.9 times higher in patients within the milder cluster compared to larger ones. CONCLUSIONS: The analysis of brain lesions in PTOD allows corroboration of smell test results and prediction of subjective and measurable improvement.

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.

A core function of the olfactory system is to determine the valence of odors. In humans, central processing of odor valence perception has been shown to take form already within the olfactory bulb (OB), but the neural mechanisms by which this important information is communicated to, and from, the olfactory cortex (piriform cortex, PC) are not known. To assess communication between the 2 nodes, we simultaneously measured odor-dependent neural activity in the OB and PC from human participants while obtaining trial-by-trial valence ratings. By doing so, we could determine when subjective valence information was communicated, what kind of information was transferred, and how the information was transferred (i.e., in which frequency band). Support vector machine (SVM) learning was used on the coherence spectrum and frequency-resolved Granger causality to identify valence-dependent differences in functional and effective connectivity between the OB and PC. We found that the OB communicates subjective odor valence to the PC in the gamma band shortly after odor onset, while the PC subsequently feeds broader valence-related information back to the OB in the beta band. Decoding accuracy was better for negative than positive valence, suggesting a focus on negative valence. Critically, we replicated these findings in an independent data set using additional odors across a larger perceived valence range. Combined, these results demonstrate that the OB and PC communicate levels of subjective odor pleasantness across multiple frequencies, at specific time points, in a direction-dependent pattern in accordance with a two-stage model of odor processing.

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.

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.

More than 50 years ago, it was proposed that breathing shapes pupil dynamics. This widespread idea is also the general understanding currently. However, there has been no attempt at synthesizing the progress on this topic since. We therefore conducted a systematic review of the literature on how breathing affects pupil dynamics in humans. We assessed the effect of breathing phase, depth, rate, and route (nose/mouth). We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, and conducted a systematic search of the scientific literature databases MEDLINE, Web of Science, and PsycInfo in November 2021. Thirty-one studies were included in the final analyses, and their quality was assessed with QualSyst. The study findings were summarized in a descriptive manner, and the strength of the evidence for each parameter was estimated following the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. The effect of breathing phase on pupil dynamics was rated as “low” (6 studies). The effect of breathing depth and breathing rate (6 and 20 studies respectively) were rated as “very low”. Breathing route was not investigated by any of the included studies. Overall, we show that there is, at best, inconclusive evidence for an effect of breathing on pupil dynamics in humans. Finally, we suggest some possible confounders to be considered, and outstanding questions that need to be addressed, to answer this fundamental question. Trial registration: This systematic review has been registered in the international prospective register of systematic reviews (PROSPERO) under the registration number: CRD42022285044. 

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.

BACKGROUND AND PURPOSE: Reduced olfactory function is the symptom with the highest prevalence in coronavirus disease 2019 (COVID-19) with nearly 70% of infected individuals experiencing partial or total loss of their sense of smell at some point during the disease. The exact cause is not known, but beyond peripheral damage, studies have demonstrated insults to both the olfactory bulb and central olfactory brain areas. However, these studies often lack both baseline pre-COVID-19 assessments and control groups, and the effects could, therefore, simply reflect pre-existing risk factors.

MATERIALS AND METHODS: Shortly before the COVID-19 outbreak, we completed an olfactory-focused study, which included structural MR brain images and a full clinical olfactory test. Opportunistically, we invited participants back 1 year later, including 9 participants who had experienced mild-to-moderate COVID-19 (C19+) and 12 who had not (C19−), creating a natural pre-post experiment with a control group.

RESULTS: Despite C19+ participants reporting subjective olfactory dysfunction, few showed signs of objectively altered function. Critically, all except 1 individual in the C19+ group had reduced olfactory bulb volume (average reduction, 14.3%), but this did not amount to a significant statistical difference compared with the control group (2.3%) using inference statistics. We found no morphologic differences in olfactory brain areas but stronger functional connectivity between olfactory brain areas in the C19+ group at the postmeasure.

CONCLUSIONS: Our data suggest that COVID-19 might cause long-term reduction in olfactory bulb volume and altered functional connectivity but with no discernible morphologic differences in cerebral olfactory regions.

Whether language is grounded in action and perception has been a key question in cognitive science, yet little attention has been given to the sense of smell. We directly test whether smell is necessary for comprehension of odor language, by comparing language processing in a group of participants with no sense of smell (anosmics) to a group of control participants. We found no evidence for a difference in online comprehension of odor and taste language between anosmics and controls using a lexical decision task and a semantic similarity judgment task, suggesting olfaction is not critical to the comprehension of odor language. Contrary to predictions, anosmics were better at remembering odor words, and rated odor and taste words as more positively valenced than control participants. This study finds no detriment to odor language after losing the sense of smell, supporting the proposal that odor language is not grounded in odor perception.