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BACKGROUND: Recent advances in the detection and treatment of prostate cancer (PCa) have reduced morbidity and mortality from this common cancer. Despite these improvements, PCa remains the second leading cause of cancer death in men in the United States. Further understanding of the genetic underpinnings of lethal PCa is required to drive risk detection and prevention and ultimately reduce mortality. We therefore set out to identify germline variants associated with cases of lethal prostate cancer (LPCa). METHODS: Using a two-stage study design, we compared whole-exome sequencing data of 550 LPCa patients to 488 healthy male controls. Men were classified as having LPCa based on medical record review. Candidate genes were identified using gene- and gene-set-based rare truncating variant association tests. Case-control burden testing through Firth's penalized logistic regression and case-gnomAD allelic burden testing through a one-sided mid-p Fisher's exact test were conducted. Each gene's p-values from these tests were combined into an omnibus p-value for candidate gene selection. In the subsequent validation stage, genes were assessed using the UK Biobank and Firth's penalized logistic regression for each ancestry, combined through meta-analysis. RESULTS: Gene-based rare variant association tests identified 12 genes nominally associated with LPCa. Rare-variant association tests identified a gene set with a significantly higher burden of truncating germline mutations in LPCa patients than controls. Combining gene- and gene-set test results, four nominally significant genes (PPP1R3A, TG, PPFIBP2, and BTN3A3) were selected as candidates. Subsequent validation using the UK Biobank found that PPP1R3A was significantly associated with LPCa risk (odds ratio 2.34, CI 1.20-4.59). Specifically, pGln662ArgfsTer7 was identified as the predominant variant in PPP1R3A among LPCa patients in our dataset. CONCLUSIONS: Both individual gene and gene-set analyses identified candidates associated with LPCa. The novel association of PPP1R3A and LPCa risk merits further investigation.
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PURPOSE: The Hereditary Colorectal Cancer/Polyposis Variant Curation Expert Panel (VCEP) was established by the International Society for Gastrointestinal Hereditary Tumours and the Clinical Genome Resource, who set out to develop recommendations for the interpretation of germline APC variants underlying Familial Adenomatous Polyposis, the most frequent hereditary polyposis syndrome. METHODS: Through a rigorous process of database analysis, literature review, and expert elicitation, the APC VCEP derived gene-specific modifications to the ACMG/AMP (American College of Medical Genetics and Genomics and Association for Molecular Pathology) variant classification guidelines and validated such criteria through the pilot classification of 58 variants. RESULTS: The APC-specific criteria represented gene- and disease-informed specifications, including a quantitative approach to allele frequency thresholds, a stepwise decision tool for truncating variants, and semiquantitative evaluations of experimental and clinical data. Using the APC-specific criteria, 47% (27/58) of pilot variants were reclassified including 14 previous variants of uncertain significance (VUS). CONCLUSION: The APC-specific ACMG/AMP criteria preserved the classification of well-characterized variants on ClinVar while substantially reducing the number of VUS by 56% (14/25). Moving forward, the APC VCEP will continue to interpret prioritized lists of VUS, the results of which will represent the most authoritative variant classification for widespread clinical use.
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Polipose Adenomatosa do Colo , Testes Genéticos , Humanos , Testes Genéticos/métodos , Variação Genética , Polipose Adenomatosa do Colo/diagnóstico , Polipose Adenomatosa do Colo/genética , Mutação em Linhagem Germinativa/genética , Células GerminativasRESUMO
Videogames are emerging as a promising experimental paradigm in neuroimaging. Acquiring gameplay in a scanner remains challenging due to the lack of a scanner-compatible videogame controller that provides a similar experience to standard, commercial devices. In this paper, we introduce a videogame controller designed for use in the functional magnetic resonance imaging as well as magnetoencephalography. The controller is made exclusively of 3D-printed and commercially available parts. We evaluated the quality of our controller by comparing it to a non-MRI compatible controller that was kept outside the scanner. The comparison of response latencies showed reliable button press accuracies of adequate precision. Comparison of the subjects' motion during fMRI recordings of various tasks showed that the use of our controller did not increase the amount of motion produced compared to a regular MR compatible button press box. Motion levels during an ecological videogame task were of moderate amplitude. In addition, we found that the controller only had marginal effect on temporal SNR in fMRI, as well as on covariance between sensors in MEG, as expected due to the use of non-magnetic building materials. Finally, the reproducibility of the controller was demonstrated by having team members who were not involved in the design build a reproduction using only the documentation. This new videogame controller opens new avenues for ecological tasks in fMRI, including challenging videogames and more generally tasks with complex responses. The detailed controller documentation and build instructions are released under an Open Source Hardware license to increase accessibility, and reproducibility and enable the neuroimaging research community to improve or modify the controller for future experiments.
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Magnetoencefalografia , Jogos de Vídeo , Humanos , Reprodutibilidade dos Testes , Imageamento por Ressonância Magnética/métodos , NeuroimagemRESUMO
Protease-activated receptor 4 (PAR4) (gene F2RL3) harbors a functional dimorphism, rs773902 A/G (encoding Thr120/Ala120, respectively) and is associated with greater platelet aggregation. The A allele frequency is more common in Black individuals, and Black individuals have a higher incidence of ischemic stroke than White individuals. However, it is not known whether the A allele is responsible for worse stroke outcomes. To directly test the in vivo effect of this variant on stroke, we generated mice in which F2rl3 was replaced by F2RL3, thereby expressing human PAR4 (hPAR4) with either Thr120 or Ala120. Compared with hPAR4 Ala120 mice, hPAR4 Thr120 mice had worse stroke outcomes, mediated in part by enhanced platelet activation and platelet-neutrophil interactions. Analyses of 7,620 Black subjects with 487 incident ischemic strokes demonstrated the AA genotype was a risk for incident ischemic stroke and worse functional outcomes. In humanized mice, ticagrelor with or without aspirin improved stroke outcomes in hPAR4 Ala120 mice, but not in hPAR4 Thr120 mice. P selectin blockade improved stroke outcomes and reduced platelet-neutrophil interactions in hPAR4 Thr120 mice. Our results may explain some of the racial disparity in stroke and support the need for studies of nonstandard antiplatelet therapies for patients expressing PAR4 Thr120.
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AVC Isquêmico , Acidente Vascular Cerebral , Humanos , Animais , Camundongos , Receptores de Trombina/genética , Agregação Plaquetária/genética , Plaquetas/fisiologia , Inibidores da Agregação Plaquetária/farmacologia , Acidente Vascular Cerebral/genética , Receptor PAR-1RESUMO
Pathogenic variants (PVs) in the SDHD gene increase risk for paragangliomas (PGL)/pheochromocytomas, renal cell carcinomas, and gastrointestinal stromal tumors. Penetrance in individuals with SDHD PVs varies in reported research from 40-70%, and there is limited evidence of specific genotype risks. This study aims to characterize a multi-generational family with SDHD p.Trp43* PVs and potential genotype-phenotype considerations for surveillance. Individuals with a paternally inherited SDHD p.Trp43*(c.129G > A) PV were identified. Genetic, medical and family histories were abstracted, including clinical characteristics, tumor histories, and treatment approaches. Eleven individuals with the SDHD PV in the same kindred were diagnosed with 41 SDHx-related tumors across all family members. Eight individuals developed 27 head and neck PGL of varying origins, and seven individuals developed tumors outside of the head and neck region. Many individuals had multiple tumors, and age of first tumor diagnosis ranged from age 10 to age 45 years old. Individuals with SDHD p.Trp43* variants may have higher risks for SDHx related tumors than other SDHD variants. Prioritizing identification of at-risk individuals and initiating surveillance tailored to family history is recommended given the rate of multiple tumors found in one familial branch of individuals under 18 years old. Individuals with strong family histories of PGL at young ages with this PV will benefit from tailored surveillance recommendations.
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Neoplasias das Glândulas Suprarrenais , Paraganglioma Extrassuprarrenal , Paraganglioma , Feocromocitoma , Humanos , Succinato Desidrogenase/genética , Paraganglioma/genética , Feocromocitoma/genética , Neoplasias das Glândulas Suprarrenais/genética , Mutação em Linhagem GerminativaRESUMO
BRCA1 is a high-risk susceptibility gene for breast and ovarian cancer. Pathogenic protein-truncating variants are scattered across the open reading frame, but all known missense substitutions that are pathogenic because of missense dysfunction are located in either the amino-terminal RING domain or the carboxy-terminal BRCT domain. Heterodimerization of the BRCA1 and BARD1 RING domains is a molecularly defined obligate activity. Hence, we tested every BRCA1 RING domain missense substitution that can be created by a single nucleotide change for heterodimerization with BARD1 in a mammalian two-hybrid assay. Downstream of the laboratory assay, we addressed three additional challenges: assay calibration, validation thereof, and integration of the calibrated results with other available data, such as computational evidence and patient/population observational data to achieve clinically applicable classification. Overall, we found that 15%-20% of BRCA1 RING domain missense substitutions are pathogenic. Using a Bayesian point system for data integration and variant classification, we achieved clinical classification of 89% of observed missense substitutions. Moreover, among missense substitutions not present in the human observational data used here, we find an additional 45 with concordant computational and functional assay evidence in favor of pathogenicity plus 223 with concordant evidence in favor of benignity; these are particularly likely to be classified as likely pathogenic and likely benign, respectively, once human observational data become available.
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Neoplasias da Mama , Neoplasias Ovarianas , Animais , Proteína BRCA1/genética , Teorema de Bayes , Neoplasias da Mama/genética , Feminino , Humanos , Mamíferos , Mutação de Sentido Incorreto/genética , Neoplasias Ovarianas/genética , Domínios ProteicosRESUMO
Hereditary leiomyomatosis and renal cell cancer (HLRCC) is an inherited cancer predisposition syndrome caused by autosomal dominant heterozygous pathogenic variants in the fumarate hydratase (FH) gene. FH pathogenic variant carriers are at an increased risk for cutaneous leiomyomas, renal cell cancer, and uterine fibroids. We present a case series of patients identified at two different medical institutions with clinically diagnostic features of HLRCC and a shared rare variant in the FH gene.
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PURPOSE: Germline mutations in DNA repair (DR) genes and susceptibility genes CDKN2A and HOXB13 have previously been associated with prostate cancer (PC) incidence and/or progression. However, the role and prevalence of this class of mutations in metastatic PC (mPC) are not fully understood. PATIENTS AND METHODS: To evaluate the frequency of pathogenic/likely pathogenic germline variants (PVs/LPVs) in men with mPC, this study sequenced 38 DR genes, CDKN2A, and HOXB13 in a predominantly white cohort of 317 patients with mPC. A PC registry at the University of Utah was used for patient sample acquisition and retrospective clinical data collection. Deep target sequencing allowed for germline and copy number variant analyses. Validated PVs/LPVs were integrated with clinical and demographic data for statistical correlation analyses. RESULTS: All pathogenic variants were found in men self-reported as white, with a carrier frequency of 8.5% (DR genes, 7.3%; CDKN2A/HOXB13, 1.2%). Consistent with previous reports, mutations were most frequently identified in the breast cancer susceptibility gene BRCA2. It was also found that 50% of identified PVs/LPVs were categorized as founder mutations with European origins. Correlation analyses did not support a trend toward more advanced or earlier-onset disease in comparisons between carriers and noncarriers of deleterious DR or HOXB13 G84E mutations. CONCLUSION: These findings demonstrate a lower prevalence of germline PVs/LPVs in an unselected, predominantly white mPC cohort than previously reported, which may have implications for the design of clinical trials testing targeted therapies. Larger studies in broad and diverse populations are needed to more accurately define the prevalence of germline mutations in men with mPC.
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Germline pathogenic mutations in DNA repair genes have been linked to prostate cancer risk and aggressiveness. This observation was facilitated by tumor sequencing of men with advanced prostate cancer and has important implications for clinical management. In addition, cascade testing will identify at-risk individuals who should be assessed for cancer risk.
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Reparo do DNA/genética , Predisposição Genética para Doença , Neoplasias da Próstata/genética , Neoplasias da Próstata/patologia , Humanos , MasculinoRESUMO
Vulnerability to obesity includes eating in response to food cues, which acquire incentive value through conditioning. The conditioning process is largely subserved by dopamine, theorized to encode the discrepancy between expected and actual rewards known as the reward prediction error (RPE). Ghrelin is a gut-derived homeostatic hormone that triggers hunger and eating. Despite extensive evidence that ghrelin stimulates dopamine, it remains unknown in humans whether ghrelin modulates food cue learning. Here, we show using fMRI that intravenously administered ghrelin increased RPE-related activity in dopamine-responsive areas during food odor conditioning in healthy volunteers. Participants responded faster to food odor-associated cues and perceived them to be more pleasant following ghrelin injection. Ghrelin also increased functional connectivity between the hippocampus and the ventral striatum. Our work demonstrates that ghrelin promotes the ability of food cues to acquire incentive salience and has implications for the development of vulnerability to obesity.
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Alimentos , Grelina/farmacologia , Imageamento por Ressonância Magnética , Odorantes , Comportamento , Condicionamento Psicológico , Sinais (Psicologia) , Hipocampo/efeitos dos fármacos , Hipocampo/fisiologia , Humanos , Neostriado/efeitos dos fármacos , Neostriado/fisiologia , Percepção/efeitos dos fármacos , Recompensa , Olfato/efeitos dos fármacosRESUMO
BACKGROUND: Few genes have germline mutations which predispose men to more aggressive prostate cancer (PCa). This study evaluated the contribution of germline loss of function (LOF) variants in PPFIBP2 to risk of lethal PCa. METHODS: A case-case study of 1414 PCa patients with lethal PCa and low-risk localized PCa was performed. Germline DNA samples from these patients were sequenced for PPFIBP2. Mutation carrier rates and association with lethal PCa were analyzed using the Fisher exact test, logistic regression, and Kaplan-Meier survival analysis. RESULTS: In the entire study population, eight patients, all of European ancestry, were identified as carrying PPFIBP2 pathogenic or likely pathogenic mutations. Seven (1.52%) of 462 lethal PCa patients were carriers compared with only one (0.12%) carrier in 810 low-risk PCa patients, P = 0.0029. The estimated Odds Ratio (OR) of carrying PPFIBP2 mutation for lethal PCa was 13.8 in European American population. The PPFIBP2 loss-of-function mutation carrier rate in lethal PCa cases was also higher than in 33 370 non-Finnish European individuals from the Exome Aggregation Consortium (ExAC) (carrier rate of 0.17%, P = 1.92 × 10-5 ) and in 498 men with localized PCa from The Cancer Genome Atlas cohort (TCGA) cohort (carrier rate of 0%, P = 0.0058). Survival analysis in European American lethal cases revealed PPFIBP2 mutation status as an independent predictor of shorter survival after adjusting for age at diagnosis, PSA at diagnosis, and genetic background (hazard ratio = 2.62, P = 0.034). CONCLUSIONS: While larger studies are needed, germline mutations in a novel gene, PPFIBP2, differentiated risk for lethal PCa from low-risk cases and were associated with shorter survival times after diagnosis.
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Proteínas de Transporte/genética , Genótipo , Proteínas de Membrana/genética , Neoplasias da Próstata/genética , Neoplasias da Próstata/mortalidade , Idoso , Predisposição Genética para Doença , Mutação em Linhagem Germinativa , Humanos , Peptídeos e Proteínas de Sinalização Intracelular , Masculino , Pessoa de Meia-Idade , Prognóstico , Próstata/patologia , Neoplasias da Próstata/patologia , Estudos Retrospectivos , Análise de Sobrevida , Taxa de SobrevidaRESUMO
Vaccination of immunocompromised patients is recommended in many national guidelines to protect against severe or complicated influenza infection. However, due to uncertainties over the evidence base, implementation is frequently patchy and dependent on individual clinical discretion. We conducted a systematic review and meta-analysis to assess the evidence for influenza vaccination in this patient group. Healthcare databases and grey literature were searched and screened for eligibility. Data extraction and assessments of risk of bias were undertaken in duplicate, and results were synthesised narratively and using meta-analysis where possible. Our data show that whilst the serological response following vaccination of immunocompromised patients is less vigorous than in healthy controls, clinical protection is still meaningful, with only mild variation in adverse events between aetiological groups. Although we encountered significant clinical and statistical heterogeneity in many of our meta-analyses, we advocate that immunocompromised patients should be targeted for influenza vaccination.
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Hospedeiro Imunocomprometido , Vacinas contra Influenza/imunologia , Influenza Humana/prevenção & controle , Vacinação/métodos , Anticorpos Antivirais/sangue , Humanos , Vacinas contra Influenza/administração & dosagemRESUMO
The incidence of phototoxicity as a side effect of ciprofloxacin appears to be increased in patients with cystic fibrosis compared to the general population (approximately 2.4%). We used an interview-based questionnaire to determine the incidence of such phototoxic skin reactions in cystic fibrosis patients. Results from 105 respondents revealed the incidence of ciprofloxacin-induced phototoxicity in the adult cystic fibrosis population in Northern Ireland to be 48.4% with only 66% of the patients recalling being given sun care information beforehand. We concluded that the incidence of phototoxicity is increased in patients with cystic fibrosis and that it is important for all to receive good sun care information prior to taking ciprofloxacin given the high risk of developing phototoxic rash.
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Anti-Infecciosos/efeitos adversos , Ciprofloxacina/efeitos adversos , Fibrose Cística/tratamento farmacológico , Dermatite Fototóxica/epidemiologia , Dermatite Fototóxica/etiologia , Adulto , Anti-Infecciosos/administração & dosagem , Ciprofloxacina/administração & dosagem , Fibrose Cística/epidemiologia , Dermatite Fototóxica/prevenção & controle , Feminino , Humanos , Masculino , Irlanda do Norte/epidemiologia , Fatores de Risco , Inquéritos e QuestionáriosRESUMO
BACKGROUND: Immunocompromised patients are vulnerable to severe or complicated influenza infection. Vaccination is widely recommended for this group. This systematic review and meta-analysis assesses influenza vaccination for immunocompromised patients in terms of preventing influenza-like illness and laboratory confirmed influenza, serological response and adverse events. METHODOLOGY/PRINCIPAL FINDINGS: Electronic databases and grey literature were searched and records were screened against eligibility criteria. Data extraction and risk of bias assessments were performed in duplicate. Results were synthesised narratively and meta-analyses were conducted where feasible. Heterogeneity was assessed using I(2) and publication bias was assessed using Begg's funnel plot and Egger's regression test. Many of the 209 eligible studies included an unclear or high risk of bias. Meta-analyses showed a significant effect of preventing influenza-like illness (odds ratio [OR]=0.23; 95% confidence interval [CI]=0.16-0.34; p<0.001) and laboratory confirmed influenza infection (OR=0.15; 95% CI=0.03-0.63; p=0.01) through vaccinating immunocompromised patie nts compared to placebo or unvaccinated controls. We found no difference in the odds of influenza-like illness compared to vaccinated immunocompetent controls. The pooled odds of seroconversion were lower in vaccinated patients compared to immunocompetent controls for seasonal influenza A(H1N1), A(H3N2) and B. A similar trend was identified for seroprotection. Meta-analyses of seroconversion showed higher odds in vaccinated patients compared to placebo or unvaccinated controls, although this reached significance for influenza B only. Publication bias was not detected and narrative synthesis supported our findings. No consistent evidence of safety concerns was identified. CONCLUSIONS/SIGNIFICANCE: Infection prevention and control strategies should recommend vaccinating immunocompromised patients. Potential for bias and confounding and the presence of heterogeneity mean the evidence reviewed is generally weak, although the directions of effects are consistent. Areas for further research are identified.
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Política de Saúde , Hospedeiro Imunocomprometido , Vacinas contra Influenza/uso terapêutico , Saúde Pública , Humanos , Vacinas contra Influenza/efeitos adversos , Vacinas contra Influenza/imunologia , PlacebosRESUMO
Chemosensory-based communication is a vital signaling tool in most species, and evidence has recently emerged in support of the notion that humans also use social chemosignals (so-called pheromones) to communicate. An ongoing controversy does exist, however, concerning the receptor organ through which these chemicals are processed. There is a widespread belief that the vomeronasal organ (VNO) is responsible for processing social chemosignals in humans. Here we demonstrate that functional occlusion of the VNO does not change the percept of, sensitivity toward, or functional neuronal processing of a putative human pheromone. Perithreshold and suprathreshold perception of the endogenous chemical androstadienone (AND) were compared, as were positron emission tomography brain activations evoked by AND when the VNO was either occluded or left open. In addition, we compared sensitivity to AND in subjects with an identifiable VNO to those in whom no VNO could be detected. Thus we could examine the effects of the VNO at several different levels of processing. Occlusion or absence of the VNO did not affect either the perceptual measurements or the functional processing of the putative human pheromone, AND. These results provide strong evidence that the human VNO has no obvious function. Pheromonal communication in humans may be conveyed via the main olfactory system.
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Odorantes , Percepção/fisiologia , Olfato/fisiologia , Órgão Vomeronasal/fisiologia , Adolescente , Adulto , Análise de Variância , Mapeamento Encefálico , Feminino , Lateralidade Funcional/fisiologia , Humanos , Medição da Dor , Tomografia por Emissão de Pósitrons/métodos , Reconhecimento Psicológico/fisiologia , Órgão Vomeronasal/diagnóstico por imagem , Adulto JovemRESUMO
We investigated associations between olfactory function and gray matter thickness in 46 healthy young subjects by means of an automated technique for measuring cortical thickness. We used an extended version of the Sniffin' Sticks test to assess olfactory function, including odor threshold, concentration discrimination, quality discrimination, and odor identification. We observed a correlation between olfactory performance and cortical thickness of structures involved in earlier and later stages of chemosensory processing such as right medial orbitofrontal cortex, right insula, and adjacent cortex. Furthermore, we found significant bilateral correlations of olfactory performance with cortical thickness of areas around the central sulcus bilaterally, structures responsible for voluntary respiration and sniffing. In addition to expected general sex effects on cortical thickness, we observed areas, such as the entorhinal cortex, occipital cortex, intraparietal sulcus and insula (all in the right hemisphere), where the correlation between higher order olfactory functions and cortical thickness differed between women and men. These data demonstrate, for some neuroanatomical structures, a link between cortical thickness and olfactory function, in that thicker cortex is usually associated with better performance, but not always. This association between anatomy and olfactory performance suggests a possible biological explanation for the high degree of individual differences and sex effects observed in higher order olfactory tasks.
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Córtex Cerebral/anatomia & histologia , Córtex Cerebral/fisiologia , Condutos Olfatórios/anatomia & histologia , Condutos Olfatórios/fisiologia , Olfato/fisiologia , Adaptação Fisiológica/fisiologia , Adulto , Mapeamento Encefálico , Discriminação Psicológica/fisiologia , Dominância Cerebral/fisiologia , Córtex Entorrinal/anatomia & histologia , Córtex Entorrinal/fisiologia , Feminino , Lateralidade Funcional/fisiologia , Humanos , Imageamento por Ressonância Magnética , Masculino , Testes Neuropsicológicos , Córtex Pré-Frontal/anatomia & histologia , Córtex Pré-Frontal/fisiologia , Psicometria , Limiar Sensorial/fisiologia , Caracteres Sexuais , Adulto JovemRESUMO
Single odors are processed differently from odor mixtures in the cortex of rodents. We investigated whether single and binary odor mixtures activate different regions also in the human brain. We analyzed data from positron emission tomography scans using pyridine, citral, and 5 mixtures of pyridine and citral in proportions varying from 10/90 to 90/10, with 50/50 being the most impure. Comparing mixtures with single odorants gave activation in the left cingulate and right parietal and superior frontal cortices and bilateral activation in the anterior and lateral orbitofrontal cortices. We also found that brain activity in the lateral orbitofrontal cortex (OFC) increased with odorant impurity, whereas the anterior OFC was activated for binary odor mixtures and deactivated for single components. We conclude that binary odor mixtures and their individual components are processed differently by the human brain. The lateral portion of the OFC responds to mixture impurity in a graded fashion, whereas the anterior portion acts like an on-off detector of odor mixtures.
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Córtex Cerebral/fisiologia , Misturas Complexas , Aprendizagem por Discriminação/fisiologia , Discriminação Psicológica/fisiologia , Potenciais Evocados/fisiologia , Odorantes , Olfato/fisiologia , Feminino , Humanos , Masculino , Adulto JovemRESUMO
The present study aimed to investigate cerebral activation following intranasal trigeminal chemosensory stimulation using O15-H2O-PET. A total of 12 healthy male participants underwent a PET scan presented with four scanning conditions; two left-sided intranasal CO(2)-stimuli and two matched baseline conditions consisting of odorless air. CO(2) was used as it produces burning and stinging sensations. Stimulation started 20 s before intravenous injection of the isotope and lasted for the first 60 s of the 5 min scan time. A comparison between CO(2) and baseline showed a pronounced activation of the trigeminal projection area at the base of the postcentral gyrus (primary and secondary somatosensory cortex) which was more intense for the right hemisphere, contralateral to the side of stimulation. In addition, activation was also found in the piriform cortex which is typically activated following odor presentation and thus thought of as primary olfactory cortex. In conclusion, and in line with previously published work, our data suggest that intranasal trigeminal stimulation not only activates somatosensory projection areas, but that it also leads to activation in cerebral areas associated with the processing of olfactory information. This may be interpreted in terms of the intimate relation between the intranasal chemosensory systems.
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Mapeamento Encefálico , Córtex Cerebral/diagnóstico por imagem , Córtex Cerebral/fisiologia , Tomografia por Emissão de Pósitrons/métodos , Nervo Trigêmeo/fisiologia , Adulto , Dióxido de Carbono/farmacologia , Lateralidade Funcional , Humanos , Masculino , Pessoa de Meia-Idade , Condutos Olfatórios/efeitos dos fármacos , Condutos Olfatórios/fisiologiaRESUMO
Kin recognition, an evolutionary phenomenon ubiquitous among phyla, is thought to promote an individual's genes by facilitating nepotism and avoidance of inbreeding. Whereas isolating and studying kin recognition mechanisms in humans using auditory and visual stimuli is problematic because of the high degree of conscious recognition of the individual involved, kin recognition based on body odors is done predominantly without conscious recognition. Using this, we mapped the neural substrates of human kin recognition by acquiring measures of regional cerebral blood flow from women smelling the body odors of either their sister or their same-sex friend. The initial behavioral experiment demonstrated that accurate identification of kin is performed with a low conscious recognition. The subsequent neuroimaging experiment demonstrated that olfactory based kin recognition in women recruited the frontal-temporal junction, the insula, and the dorsomedial prefrontal cortex; the latter area is implicated in the coding of self-referent processing and kin recognition. We further show that the neuronal response is seemingly independent of conscious identification of the individual source, demonstrating that humans have an odor based kin detection system akin to what has been shown for other mammals.
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Encéfalo/fisiologia , Família , Percepção Olfatória/fisiologia , Reconhecimento Fisiológico de Modelo , Reconhecimento Psicológico/fisiologia , Encéfalo/diagnóstico por imagem , Mapeamento Encefálico , Feminino , Amigos , Humanos , Odorantes , Estimulação Física , Tomografia por Emissão de Pósitrons , Irmãos , Análise e Desempenho de Tarefas , Adulto JovemRESUMO
We examined whether presenting an odor with a positive, neutral, or negative name would influence how people perceive it. In experiment 1, 40 participants rated 15 odors for their pleasantness, intensity, and arousal. In experiment 2, 30 participants passively smelled 10 odors while their skin conductance (SC), heart rate (HR), and sniffing were recorded. We found significant overall effects of odor names on perceived pleasantness, intensity, and arousal. Pleasantness showed the most robust effect of odor names: the same odors were perceived as more pleasant when presented with positive than with neutral and negative names and when presented with neutral than with negative names. In addition, odorants were rated as more intense when presented with negative than with neutral and positive names and as more arousing when presented with positive than with neutral names. Furthermore, SC and sniff volumes, but not HR, were modified by odor names, and the SC changes could not be accounted for by sniffing changes. Importantly, odor names presented with odorless water did not produce any effect on skin conductance and sniff volumes, ruling out the possibility that the naming-related findings were triggered by an emotional reaction to odor names. Taken together, these experiments show that there is a lot to a name, at least when it comes to olfactory perception.