Neural Pathways Research Articles

Microbiome signature, immune landscape and global methylation in early onset colorectal cancer.

3580 Background: The incidence of colorectal cancer (CRC) in young adults (age at diagnosis < 50 years old) has been rapidly increasing. Approximately 20% of early-onset (EO) CRC cases are due to germline gene mutations. However, the etiology of sporadic EO CRC remains poorly understood. Research suggests that environmental factors such as Western diet may be associated with increased incidence of sporadic EO CRC. The gut microbiota decomposes and ferments dietary fibers to produce microbial metabolites, which play important roles in maintaining the intestinal epithelium integrity. A high-fat, low-fiber diet has been associated with intestinal dysbiosis, which disrupts intestinal bacterial homeostasis. An increased inflammation state characterizes dysbiosis and may promote an immunosuppressive tumor microenvironment (TME) and suppress antitumor immune surveillance. In addition, epigenetic modifications are influenced by environmental changes and therefore epigenetics may bridge the knowledge gap in understanding the development of sporadic EOCRC. Methods: We obtained RNA sequencing data from the Cancer Genome Atlas (TCGA) and the Oncology Research Information Exchange Network (ORIEN) from the Ohio State University biospecimen services to characterize intra-tumor microbiota composition, tumor-infiltrating lymphocytes (TILs) and differential pathways in EO CRC. We used Infinium HM450 methylation array in The Cancer Genome Atlas (TCGA) and performed genome-wide analyses using reduced representation bisulfite sequencing (RRBS) method to identify differentially methylated regions (DMRs) in EO CRC. Results: Gene expression analysis is consistent with Fusobacterium promoting inflammation in EO CRC. Intra-tumor microbes are positively correlated with M2 macrophages. Compared to late onset (LO) CRC, EO CRC patients have unique gene signatures of phagosome formation, S100 family signaling pathway and CREB signaling in neurons by using ingenuity pathway analysis (IPA). In addition, we found that methylation ages predicted by epigenetic clocks in EO CRC patients were 15 years older on average than their chronological ages, whereas methylation ages in late onset (LO) CRC patients were comparable with chronological ages. The enriched pathways based on DMRs associated with EO CRC have significant overlap with canonical pathways based on differentially expressed genes (DEGs), including CREB signaling in neurons and S100 family signaling pathways. Conclusions: These data suggest that pathogenic microbes may induce inflammation, which leads to accelerated aging in EO CRC.

A neural m6A pathway regulates behavioral aggregation in migratory locusts.

RNA N6-methyladenosine (m6A), as the most abundant modification of messenger RNA, can modulate insect behaviors, but its specific roles in aggregation behaviors remain unexplored. Here, we conducted a comprehensive molecular and physiological characterization of the individual components of the methyltransferase and demethylase in the migratory locust Locusta migratoria. Our results demonstrated that METTL3, METTL14 and ALKBH5 were dominantly expressed in the brain and exhibited remarkable responses to crowding or isolation. The individual knockdown of methyltransferases (i.e., METTL3 and METTL14) promoted locust movement and conspecific attraction, whereas ALKBH5 knockdown induced a behavioral shift toward the solitary phase. Furthermore, global transcriptome profiles revealed that m6A modification could regulate the orchestration of gene expression to fine tune the behavioral aggregation of locusts. In summary, our in vivo characterization of the m6A functions in migratory locusts clearly demonstrated the crucial roles of the m6A pathway in effectively modulating aggregation behaviors.

Dexmedetomidine-mediated improvement of perioperative neurocognitive disorders by miR-184-3p-mediated NLRP3

BackgroundPerioperative neurocognitive disorders (PND) is a neurological complication in the perioperative period, which may lead to severe poor prognosis. Dexmedetomidine (Dex) is a commonly used sedative in the perioperative period. However, the effect of intraoperative anesthetic Dex on PND remains complicated and confusing. MethodsPND model was established using aged male mice, treated with Dex, and subjected to behavioral tests. The effect of Dex on pyroptosis was assessed by western blot, enzyme-linked immunosorbent assay and immunofluorescence. In addition, the miRNA expression profile of PND mice was identified by small RNA sequencing and performed PCR to detect miRNAs. Finally, the effect of miRNA on mice neuron pyroptosis was verified in vitro. ResultsWe found postoperative cognitive was declined in PND mice compared with control group, while preoperative injection of Dex improved short-term working memory and anxious exploration behavior, alleviated the cognitive impairment. Intriguingly, Dex ameliorated hippocampal inflammation and neuron pyroptosis in PND mice as evidenced by the reduced GSDMD, NLRP3, IL-1β and IL-18. The miRNA expression profile of PND mice hippocampus was disordered, including 5 miRNAs up-regulated and 17 miRNAs down-regulated, compared to the sham group. Dysregulated miRNAs were mainly enriched in biological functions related to neuronal development and signaling pathways related to pyroptosis. MiR-184-3p was the key miRNA, overexpression of miR-184-3p blocked the inhibitory effect of Dex on neuron pyroptosis, which was manifested as increased expression of GSDMD and NLRP3, increased inflammatory factors IL-1β and IL-18. ConclusionsThis study revealed that miR-184-3p may mediate NLRP3 to prevent the alleviating effect of Dex on PND, which provides a new potential way to improve the therapeutic intervention of PND.

Cognitive decline in Sprague-Dawley rats induced by neuroplasticity changes after occlusal support loss.

Tooth loss is closely related to cognitive impairment, especially affecting cognitive functions involving hippocampus. The most well-known function of the hippocampus is learning and memory, and the mechanism behind is neuroplasticity, which strongly depends on the level of brain-derived neurotrophic factor (BDNF). While research has delved into the possible mechanisms behind the loss of teeth leading to cognitive dysfunction, there are few studies on the plasticity of sensory neural pathway after tooth loss, and the changes in related indicators of synaptic plasticity still need to be further explored. In this study, the bilateral maxillary molars were extracted in Sprague-Dawley rats of two age ranges (young and middle age) to establish occlusal support loss model; then, the spatial cognition was tested by Morris Water Maze (MWM). Quantitative real-time PCR (qPCR) and Western Blotting (WB) were used to detect BDNF, AKT, and functional proteins (viz., PSD95 and NMDAR) of hippocampal synapses. Golgi staining was used to observe changes in ascending nerve pathway. IF was used to confirm the location of BDNF and AKT expressed in hippocampus. MWM showed that the spatial cognitive level of rats dropped after occlusal support loss. qPCR, WB, and IF suggested that the BDNF/AKT pathway was down-regulated in the hippocampus. Golgi staining showed the neurons of ascending sensory pathway decreased in numbers. Occlusal support loss caused plastic changes in ascending nerve pathway and induced cognitive impairment in rats by down-regulating BDNF and synaptic plasticity.

Speech decoding from stereo-electroencephalography (sEEG) signals using advanced deep learning methods

Objective. Brain–computer interfaces (BCIs) are technologies that bypass damaged or disrupted neural pathways and directly decode brain signals to perform intended actions. BCIs for speech have the potential to restore communication by decoding the intended speech directly. Many studies have demonstrated promising results using invasive micro-electrode arrays and electrocorticography. However, the use of stereo-electroencephalography (sEEG) for speech decoding has not been fully recognized. Approach. In this research, recently released sEEG data were used to decode Dutch words spoken by epileptic participants. We decoded speech waveforms from sEEG data using advanced deep-learning methods. Three methods were implemented: a linear regression method, an recurrent neural network (RNN)-based sequence-to-sequence model (RNN), and a transformer model. Main results. Our RNN and transformer models outperformed the linear regression significantly, while no significant difference was found between the two deep-learning methods. Further investigation on individual electrodes showed that the same decoding result can be obtained using only a few of the electrodes. Significance. This study demonstrated that decoding speech from sEEG signals is possible, and the location of the electrodes is critical to the decoding performance.

The role of hidden hearing loss in tinnitus: Insights from early markers of peripheral hearing damage

Since the presence of tinnitus is not always associated with audiometric hearing loss, it has been hypothesized that hidden hearing loss may act as a potential trigger for increased central gain along the neural pathway leading to tinnitus perception. In recent years, the study of hidden hearing loss has improved with the discovery of cochlear synaptopathy and several objective diagnostic markers. This study investigated three potential markers of peripheral hidden hearing loss in subjects with tinnitus: extended high-frequency audiometric thresholds, the auditory brainstem response, and the envelope following response. In addition, speech intelligibility was measured as a functional outcome measurement of hidden hearing loss. To account for age-related hidden hearing loss, participants were grouped according to age, presence of tinnitus, and audiometric thresholds. Group comparisons were conducted to differentiate between age- and tinnitus-related effects of hidden hearing loss. All three markers revealed age-related differences, whereas no differences were observed between the tinnitus and non-tinnitus groups. However, the older tinnitus group showed improved performance on low-pass filtered speech in noise tests compared to the older non-tinnitus group. These low-pass speech in noise scores were significantly correlated with tinnitus distress, as indicated using questionnaires, and could be related to the presence of hyperacusis. Based on our observations, cochlear synaptopathy does not appear to be the underlying cause of tinnitus. The improvement in low-pass speech-in-noise could be explained by enhanced temporal fine structure encoding or hyperacusis. Therefore, we recommend that future tinnitus research takes into account age-related factors, explores low-frequency encoding, and thoroughly assesses hyperacusis.

Natural Compounds that Modulate Circadian Rhythms.

Circadian rhythms of innate 24 h cycles comprise well-conserved biological phenomena from cyanobacteria to mammalian. They are driven by light and regulated by clock genes that work as transcription factors and control the expression of many other genes and physiological functions in the cells. The expression of ~ 40% of protein-coding genes shows 24 h oscillation patterns in mice, implying their importance in normal body functions. Indeed, the physiological and behavioural rhythmicity generated through clock genes-mediated multiple mechanisms affects the quality of life at large. Disrupted circadian rhythmicity is associated with several kinds of diseases. For example, cancer cells show abnormal expression patterns for circadian rhythm genes that have been shown to regulate oncogenesis, drug responses, and disease prognosis. Furthermore, the modern globalisation of human lifestyle and business and social activities have disrupted innate circadian rhythm, resulting in a variety of diseases through disrupted humoral, immunological, and neuronal pathways. Safe and sustainable modulation of circadian rhythm has become a prevalent need that warrants basic and interventional research, as well as clinical investigations. Although traditional systems of medicine suggest some natural compounds with circadian rhythmmodulating potential, most of these have not been validated in laboratory or clinical studies. Reliable read-outs of the effects of test compounds on circadian rhythmicity have been limited by the availability of live cell assays. We have, herein, provided an overview of living cell-embedded real- time reporter gene assays designed for screening compounds that modulate circadian rhythm, and discussed the potential of some natural compounds for circadian rhythm modulation as validated by cell-based assay systems, and their role in disease therapeutics.

What Is a Visual Stream?

The dual stream model of the human and non-human primate visual systems remains Leslie Ungerleider's (1946-2020) most indelible contribution to visual neuroscience. In this model, a dorsal "where" stream specialized for visuospatial representation extends through occipitoparietal cortex, whereas a ventral "what" stream specialized for representing object qualities extends through occipito-temporal cortex. Over time, this model underwent a number of revisions and expansions. In one of her last scientific contributions, Leslie proposed a third visual stream specialized for representing dynamic signals related to social perception. This alteration invites the question: What is a visual stream, and how are different visual streams individuated? In this article, we first consider and reject a simple answer to this question based on a common idealizing visualization of the model, which conflicts with the complexities of the visual system that the model was intended to capture. Next, we propose a taxonomic answer that takes inspiration from the philosophy of science and Leslie's body of work, which distinguishes between neural mechanisms, pathways, and streams. In this taxonomy, visual streams are superordinate to pathways and mechanisms and provide individuation conditions for determining whether collections of cortical connections delineate different visual streams. Given this characterization, we suggest that the proposed third visual stream does not yet meet these conditions, although the tripartite model still suggests important revisions to how we think about the organization of the human and non-human primate visual systems.

Transforming growth factor-β1 protects mechanically injured cortical murine neurons by reducing trauma-induced autophagy and apoptosis.

Transforming growth factor β1 (TGF-β1) has a neuroprotective function in traumatic brain injury (TBI) through its anti-inflammatory and immunomodulatory properties. However, the precise mechanisms underlying the neuroprotective actions of TGF-β1 on the cortex require further investigation. In this study, we were aimed to investigate the regulatory function of TGF-β1 on neuronal autophagy and apoptosis using an in vitro primary cortical neuron trauma-injury model. LDH activity was assayed to measure cell viability, and intracellular [Ca2+] was measured using Fluo-4-AM in an in vitro primary cortical neuron trauma-injury model. RNA-sequencing (RNAseq), immunofluorescent staining, transmission electron microscopy (TEM), western blot and CTSD activity detection were employed. We observed significant enrichment of DEGs related to autophagy, apoptosis, and the lysosome pathway in trauma-injured cortical neurons. TEM confirmed the presence of autophagosomes as well as autophagolysosomes. Western blot revealed upregulation of autophagy-related protein light chain 3 (LC3-II/LC3-I), sequestosome 1 (SQSTM1/p62), along with apoptosis-related protein cleaved-caspase 3 in trauma-injured primary cortical neurons. Furthermore, trauma-injured cortical neurons showed an upregulation of lysosomal marker protein (LAMP1) and lysosomal enzyme mature cathepsin D (mCTSD), but a decrease in the activity of CTSD enzyme. These results indicated that apoptosis was up-regulated in trauma- injured cortical neurons at 24 h, accompanied by lysosomal dysfunction and impaired autophagic flux. Notably, TGF-β1 significantly reversed these changes. Our results suggested that TGF-β1 exerted neuroprotective effects on trauma- injured cortical neurons by reducing lysosomal dysfunction, decreasing the accumulation of autophagosomes and autophagolysosomes, and enhancing autophagic flux.

Modulation of the Association Between Corticospinal Tract Damage and Outcome After Stroke by White Matter Hyperintensities.

Motor outcomes after stroke relate to corticospinal tract (CST) damage. The brain leverages surviving neural pathways to compensate for CST damage and mediate motor recovery. Thus, concurrent age-related damage from white matter hyperintensities (WMHs) might affect neurologic capacity for recovery after CST injury. The role of WMHs in post-stroke motor outcomes is unclear. In this study, we evaluated whether WMHs modulate the relationship between CST damage and post-stroke motor outcomes. We used data from the multisite ENIGMA Stroke Recovery Working Group with T1 and T2/fluid-attenuated inversion recovery imaging. CST damage was indexed with weighted CST lesion load (CST-LL). WMH volumes were extracted with Freesurfer's SAMSEG. Mixed-effects beta-regression models were fit to test the impact of CST-LL, WMH volume, and their interaction on motor impairment, controlling for age, days after stroke, and stroke volume. A total of 223 individuals were included. WMH volume related to motor impairment above and beyond CST-LL (β = 0.178, 95% CI 0.025-0.331, p = 0.022). Relationships varied by WMH severity (mild vs moderate-severe). In individuals with mild WMHs, motor impairment related to CST-LL (β = 0.888, 95% CI 0.604-1.172, p < 0.001) with a CST-LL × WMH interaction (β = -0.211, 95% CI -0.340 to -0.026, p = 0.026). In individuals with moderate-severe WMHs, motor impairment related to WMH volume (β = 0.299, 95% CI 0.008-0.590, p = 0.044), but did not significantly relate to CST-LL or a CST-LL × WMH interaction. WMHs relate to motor outcomes after stroke and modify relationships between motor impairment and CST damage. WMH-related damage may be under-recognized in stroke research as a factor contributing to variability in motor outcomes. Our findings emphasize the importance of brain structural reserve in motor outcomes after brain injury.

Urban flood prediction using ensemble artificial neural network: an investigation on improving model uncertainty

Reducing the impact of artificial neural networks (ANN) affected by sources of uncertainty is crucial to improving the reliability of the flood prediction model. This study proposes an ensemble artificial neural network (EANN) model to predict the degree of flooding in coastal cities. Combined methods are used to reduce the model’s uncertainty, heuristic neural pathway strength feature selection is used to select inputs, the coupling method is used to optimize network architecture and parameters, and the integration method which paralleling three ANN models with different predicted lead periods ensemble together is used to capture output uncertainty. The EANN model has successfully predicted flooding in the Chinese coastal city of Macao during a typhoon, with convincing accuracy. The study also analyzed the impacts of both long and short training datasets with appropriate time intervals on ANN modeling performance. It was found that the performance of short training datasets, with appropriate time intervals, was similar to or better than models with long training datasets.

Negative impacts of social isolation on behavior and neuronal functions are recovered after short-term social reintroduction in zebrafish

Recently, social isolation measures were crucial to prevent the spread of the coronavirus pandemic. However, the lack of social interactions affected the population mental health and may have long-term consequences on behavior and brain functions. Here, we evaluated the behavioral, physiological, and molecular effects of a social isolation (SI) in adult zebrafish, and whether the animals recover such changes after their reintroduction to the social environment. Fish were submitted to 12 days of SI, and then reintroduced to social context (SR). Behavioral analyses to evaluate locomotion, anxiety-like and social-related behaviors were performed after SI protocol, and 3 and 6 days after SR. Cortisol and transcript levels from genes involved in neuronal homeostasis (c-fos, egr, bdnf), and serotonergic (5-HT) and dopaminergic (DA) neurotransmission (thp, th) were also measured. SI altered social behaviors in zebrafish such as aggression, social preference, and shoaling. Fish submitted to SI also presented changes in the transcript levels of genes related to neural activity, and 5-HT/DA signaling. Interestingly, most of the behavioral and molecular changes induced by SI were not found again 6 days after SR. Thus, we highlight that SR of zebrafish to their conspecifics played a positive role in social behaviors and in the expression of genes involved in different neuronal signaling pathways that were altered after 12 days of SI. This study brings unprecedented data on the effects of SR in the recovery from SI neurobehavioral alterations, and reinforces the role of zebrafish as a translational model for understanding the neurobiological mechanisms adjacent to SI and resocialization.

Unlocking new avenues for neuropsychiatric disease therapy: the emerging potential of Peroxisome proliferator-activated receptors as promising therapeutic targets.

Peroxisome proliferator-activated receptors (PPARs) are transcription factors that regulate variousphysiological processes such as inflammation, lipid metabolism, and glucose homeostasis. Recent studies suggestthat targeting PPARs could be beneficial in treating neuropsychiatric disorders by modulating neuronal function andsignaling pathways in the brain. PPAR-α, PPAR-δ, and PPAR-γ have been found to play important roles incognitive function, neuroinflammation, and neuroprotection. Dysregulation of PPARs has been associated withneuropsychiatric disorders like bipolar disorder, schizophrenia, major depression disorder, and autism spectrumdisorder. The limitations and side effects of current treatments have prompted research to target PPARs as apromising novel therapeutic strategy. Preclinical and clinical studies have shown the potential of PPAR agonistsand antagonists to improve symptoms associated with these disorders. This review aims to provide an overview of the current understanding of PPARs in neuropsychiatricdisorders, their potential as therapeutic targets, and the challenges and future directions for developingPPAR-basedtherapies. An extensive literature review of various search engines like PubMed, Medline, Bentham, Scopus, andEMBASE (Elsevier) databases was carried out with the keywords "PPAR, Neuropsychiatric disorders, Oxidativestress, Inflammation, Bipolar Disorder, Schizophrenia, Major depression disorder, Autism spectrum disorder,molecular pathway". Although PPARs present a hopeful direction for innovative therapeutic approaches inneuropsychiatric conditions, additional research is required to address obstacles and convert this potential intoclinically viable and individualized treatments.

Neural adaptations to congenital deafness: enhanced tactile discrimination through cross-modal neural plasticity - an fMRI study.

This study explores the compensatory neural mechanisms associated with congenital deafness through anexamination of tactile discrimination abilities using high-resolution functional magnetic resonance imaging (fMRI). To analyze the neural substrates underlying tactile processing in congenitally deaf individuals and compare themwith hearing controls. Our participant pool included thirty-five congenitally deaf individuals and thirty-five hearing controls. All participantsengaged in tactile discrimination tasks involving the identification of common objects by touch. We utilized ananalytical suite comprising voxel-based statistics, functional connectivity multivariate/voxel pattern analysis (fc-MVPA), and seed-based connectivity analysis to examine neural activity. Our findings revealed pronounced neural activity in congenitally deaf participants within regions typically associatedwith auditory processing, including the bilateral superior temporal gyrus, right middle temporal gyrus, and rightrolandic operculum. Additionally, unique activation and connectivity patterns were observed in the right insula andbilateral supramarginal gyrus, indicating a strategic reorganization of neural pathways for tactile informationprocessing. Behaviorally, both groups demonstrated high accuracy in the tactile tasks, exceeding 90%. However, thedeaf participants outperformed their hearing counterparts in reaction times, showcasing significantly enhancedefficiency in tactile information processing. These insights into the brain's adaptability to sensory loss through compensatory neural reorganization highlight theintricate mechanisms by which tactile discrimination is enhanced in the absence of auditory input. Understandingthese adaptations can help develop strategies to harness the brain's plasticity to improve sensory processing inindividuals with sensory impairments, ultimately enhancing their quality of life through improved tactile perceptionand sensory integration.

An In Silico Analysis of Genetic Variants and Structural Modeling of the Human Frataxin Protein in Friedreich's Ataxia.

Friedreich's Ataxia (FRDA) stands out as the most prevalent form of hereditary ataxias, marked by progressive movement ataxia, loss of vibratory sensitivity, and skeletal deformities, severely affecting daily functioning. To date, the only medication available for treating FRDA is Omaveloxolone (Skyclarys®), recently approved by the FDA. Missense mutations within the human frataxin (FXN) gene, responsible for intracellular iron homeostasis regulation, are linked to FRDA development. These mutations induce FXN dysfunction, fostering mitochondrial iron accumulation and heightened oxidative stress, ultimately triggering neuronal cell death pathways. This study amalgamated 226 FXN genetic variants from the literature and database searches, with only 18 previously characterized. Predictive analyses revealed a notable prevalence of detrimental and destabilizing predictions for FXN mutations, predominantly impacting conserved residues crucial for protein function. Additionally, an accurate, comprehensive three-dimensional model of human FXN was constructed, serving as the basis for generating genetic variants I154F and W155R. These variants, selected for their severe clinical implications, underwent molecular dynamics (MD) simulations, unveiling flexibility and essential dynamic alterations in their N-terminal segments, encompassing FXN42, FXN56, and FXN78 domains pivotal for protein maturation. Thus, our findings indicate potential interaction profile disturbances in the FXN42, FXN56, and FXN78 domains induced by I154F and W155R mutations, aligning with the existing literature.

Advances in the application of fecal microbiota transplantation for the treatment of nervous system diseases

The intestinal microbiota exhibits a strong correlation with the function of the central nervous system, exerting influence on the host brain through neural pathways, immune pathways, and microbial metabolites along the gut-brain axis. Disorders in the composition of the intestinal microbial are closely associated with the onset and progression of neurological disorders, such as depression, Alzheimer's disease, and Parkinson's disease. It has been proven that fecal microbiota transplantation can improve symptoms in animal models of neurological diseases and clinical patients. This paper provides a comprehensive review of the composition and function of the human intestinal microbiota, as well as the intricate the relationship between the human intestinal microbiota and nervous system diseases through the gut-brain axis. Additionally, it delves into the research advancements and underlying mechanism of fecal microbiota transplantation in the treatment of nervous system diseases. These findings offer novel insights and potential avenues for clinical interventions targeting nervous system diseases.

Binocularly suppressed stimuli induce brain activities related to aesthetic emotions

IntroductionAesthetic emotions are a class of emotions aroused by evaluating aesthetically appealing objects or events. While evolutionary aesthetics suggests the adaptive roles of these emotions, empirical assessments are lacking. Previous neuroscientific studies have demonstrated that visual stimuli carrying evolutionarily important information induce neural responses even when presented non-consciously. To examine the evolutionary importance of aesthetic emotions, we conducted a neuroscientific study using magnetoencephalography (MEG) to measure induced neural responses to non-consciously presented portrait paintings categorised as biological and non-biological and examined associations between the induced responses and aesthetic ratings.MethodsMEG and pre-rating data were collected from 23 participants. The pre-rating included visual analogue scales for object saliency, facial saliency, liking, and beauty scores, in addition to ‘biologi-ness,’ which was used for subcategorising stimuli into biological and non-biological. The stimuli were presented non-consciously using a continuous flash suppression paradigm or consciously using binocular presentation without flashing masks, while dichotomic behavioural responses were obtained (beauty or non-beauty). Time-frequency decomposed MEG data were used for correlation analysis with pre-rating scores for each category.ResultsBehavioural data revealed that saliency scores of non-consciously presented stimuli influenced dichotomic responses (beauty or non-beauty). MEG data showed that non-consciously presented portrait paintings induced spatiotemporally distributed low-frequency brain activities associated with aesthetic ratings, which were distinct between the biological and non-biological categories and conscious and non-conscious conditions.ConclusionAesthetic emotion holds evolutionary significance for humans. Neural pathways are sensitive to visual images that arouse aesthetic emotion in distinct ways for biological and non-biological categories, which are further influenced by consciousness. These differences likely reflect the diversity in mechanisms of aesthetic processing, such as processing fluency, active elaboration, and predictive processing. The aesthetic processing of non-conscious stimuli appears to be characterised by fluency-driven affective processing, while top-down regulatory processes are suppressed. This study provides the first empirical evidence supporting the evolutionary significance of aesthetic processing.

A neural pathway integrating stress and feeding.

A neural pathway integrating stress and feeding.

Orexin Facilitates the Peripheral Chemoreflex via Corticotropin-Releasing Hormone Neurons Projecting to the Nucleus of the Solitary Tract.

We previously showed that orexin neurons are activated by hypoxia and facilitate the peripheral chemoreflex (PCR)-mediated hypoxic ventilatory response (HVR), mostly by promoting the respiratory frequency response. Orexin neurons project to the nucleus of the solitary tract (nTS) and the paraventricular nucleus of the hypothalamus (PVN). The PVN contributes significantly to the PCR and contains nTS-projecting corticotropin-releasing hormone (CRH) neurons. We hypothesized that in male rats, orexin neurons contribute to the PCR by activating nTS-projecting CRH neurons. We used neuronal tract tracing and immunohistochemistry (IHC) to quantify the degree that hypoxia activates PVN-projecting orexin neurons. We coupled this with orexin receptor (OxR) blockade with suvorexant (Suvo, 20 mg/kg, i.p.) to assess the degree that orexin facilitates the hypoxia-induced activation of CRH neurons in the PVN, including those projecting to the nTS. In separate groups of rats, we measured the PCR following systemic orexin 1 receptor (Ox1R) blockade (SB-334867; 1 mg/kg) and specific Ox1R knockdown in PVN. OxR blockade with Suvo reduced the number of nTS and PVN neurons activated by hypoxia, including those CRH neurons projecting to nTS. Hypoxia increased the number of activated PVN-projecting orexin neurons but had no effect on the number of activated nTS-projecting orexin neurons. Global Ox1R blockade and partial Ox1R knockdown in the PVN significantly reduced the PCR. Ox1R knockdown also reduced the number of activated PVN neurons and the number of activated tyrosine hydroxylase neurons in the nTS. Our findings suggest orexin facilitates the PCR via nTS-projecting CRH neurons expressing Ox1R.

Effectiveness of post-burn pruritis treatment and improvement of insomnia - a randomized trial.

Post-burn pruritis is difficult to assess and treat. Antihistamines used in its treatment provide little relief. Identification of the itch neuronal pathway has inspired new alternatives including gabapentin in its management. The study compared the effectiveness of cetirizine, gabapentin, and a combination of gabapentin and cetirizine in treating post-burn pruritus. Burn patients were randomly assigned to treatment with Cetirizine (n=23), Gabapentin (n=23), or Cetirizine plus Gabapentin (n=23). Baseline assessment of the intensity or the severity of pruritus was evaluated after which treatment commenced with standard doses of the three study regimens. Quality of sleep was assessed at baseline (day 0) and repeated on day 3, day 7 and day 14. Approximately 97% of participants presented with moderate or severe itch; 69% with acute itch; and majority (94.2%) experienced pruritus between the first and fourth weeks. Gabapentin reduced itch by 92.9% in 14 days compared to cetirizine's 61.8%. The combined effect of cetirizine and gabapentin was comparable to using gabapentin alone. When itch became protracted over 6 weeks, the effectiveness of cetirizine in controlling itch worsened. It reduced itch intensity by only 37.7% whilst gabapentin did so at 89.4%. Itch intensity correlated positively with insomnia and controlling itch intensity improved sleep. Gabapentin was more effective for the treatment of post-burn pruritus than cetirizine. Controlling itch intensity improved sleep. In acute and moderate itch, a low-dose gabapentin could be added if cetirizine is the drug intended for its treatment.