Neurophysiological Pathways Research Articles

A multi-omics Mendelian randomization study identifies new therapeutic targets for alcohol use disorder and problem drinking.

Integrating proteomic and transcriptomic data with genetic architectures of problematic alcohol use and alcohol consumption behaviours can advance our understanding and help identify therapeutic targets. We conducted systematic screens using genome-wise association study data from ~3,500 cortical proteins (N = 722) and ~6,100 genes in 8 canonical brain cell types (N = 192) with 4 alcohol-related outcomes (N ≤ 537,349), identifying 217 cortical proteins and 255 cell-type genes associated with these behaviours, with 36 proteins and 37 cell-type genes being new. Although there was limited overlap between proteome and transcriptome targets, downstream neuroimaging revealed shared neurophysiological pathways. Colocalization with independent genome-wise association study data further prioritized 16 proteins, including CAB39L and NRBP1, and 12 cell-type genes, implicating mechanisms such as mTOR signalling. In addition, genes such as SAMHD1, VIPAS39, NUP160 and INO80E were identified as having favourable neuropsychiatric profiles. These findings provide insights into the genetic landscapes governing problematic alcohol use and alcohol consumption behaviours, highlighting promising therapeutic targets for future research.

The Contribution of the Brain-Gut Axis to the Human Reward System.

The human reward network consists of interconnected brain regions that process stimuli associated with satisfaction and modulate pleasure-seeking behaviors. Impairments in reward processing have been implicated in several medical and psychiatric conditions, and there is a growing interest in disentangling the underlying pathophysiological mechanisms. The brain-gut axis plays a regulatory role in several higher-order neurophysiological pathways, including reward processing. In this context, the aim of the current review was to critically appraise research findings on the contribution of the brain-gut axis to the human reward system. Enteric neuropeptides, which are implicated in the regulation of hunger and satiety, such as ghrelin, PYY3-36, and glucagon-like peptide 1 (GLP-1), have been associated with the processing of food-related, alcohol-related, and other non-food-related rewards, maintaining a delicate balance between the body's homeostatic and hedonic needs. Furthermore, intestinal microbiota and their metabolites have been linked to differences in the architecture and activation of brain reward areas in obese patients and patients with attention deficit and hyperactivity disorder. Likewise, bariatric surgery reduces hedonic eating by altering the composition of gut microbiota. Although existing findings need further corroboration, they provide valuable information on the pathophysiology of reward-processing impairments and delineate a novel framework for potential therapeutic interventions.

Neurophysiological Pathways of Unconscious Emotion Processing in Depression: Insights From a Simultaneous Electroencephalography–Functional Magnetic Resonance Imaging Measurement

BackgroundMajor depressive disorder (MDD) is characterized by strong emotional dysregulation. Mechanisms driving the negative affect in depression may be fast processes existing on an unconscious level. MethodsA priming task was conducted using simultaneous electroencephalography–functional magnetic resonance imaging measurement involving presentation of facial expressions (happy, sad, and neutral) to examine the neurophysiological pathway of biased unconscious emotion processing in MDD. Priming prior to a target emotion created unconscious (16.7-ms primer) and conscious (150-ms primer) trials. A large sample (N = 126) was recruited, containing healthy control participants (n = 66; 37 women) and participants with MDD (n = 60; 31 women). ResultsThe healthy control group showed a shorter reaction time in happy but not in sad or neutral trials compared with the MDD group. N170 amplitudes were lower in trials with unconscious than conscious primer presentation. N170 amplitudes correlated with cortical (right fusiform gyrus, right middle temporal gyrus, right inferior temporal gyrus, left supplementary motor area, right middle frontal gyrus) and subcortical brain regions (right amygdala). The strength of N170 and brain activity correlation increased when the stimulus was consciously presented. Presented emotions did not affect the correlation of N170 values and brain activity. ConclusionsOur findings show that MDD may exhibit biased emotion regulation abilities at a behavioral and neurophysiological level. Face-sensitive event-related potentials demonstrate a correlation with heightened brain activity in regions associated with both face recognition (fusiform gyrus) and emotion processing (amygdala). These findings are evident in both MDD and healthy control groups, with lower effect sizes in the MDD group indicating reduced emotion recognition and processing abilities.

Abstract 6924: Structural variant dynamics in melanoma: Unraveling tumor heterogeneity and evolution

Abstract Melanoma is characterized by significant intratumoral heterogeneity and complex evolutionary dynamics. This diversity in genomic alterations leads to the emergence of various subclonal populations within a single tumor. In our research, we established a new model system composed of 24 single-cell-derived clonal sublines (C1-C24), originating from the M4 melanoma model. This model was developed using a genetically engineered hepatocyte growth factor (HGF)-transgenic mouse. We employed Trisicell (Triple-toolkit for single-cell intratumor heterogeneity inference), a cutting-edge computational tool for scalable analysis of intratumor heterogeneity and evaluation based on single-cell RNA mutations. This enabled us to construct a phylogeny tree, revealing melanoma’s intricate branching evolutionary patterns. These patterns show ancestral clones evolving into genetically distinct subclones, which demonstrate varied phenotypic traits such as drug sensitivity or resistance, cellular plasticity, and immunogenicity. In our study, we conducted long-read sequencing on these clonal sublines in the phylogeny and identified structural variants (SVs) using Severus, a tool optimized for phasing in long-read sequencing. The types of SVs we discovered include deletions, insertions, amplifications, translocations, and inversions. We explored their roles in subclonal evolution, particularly focusing on how they disrupt genes and accumulate during melanoma progression. Our initial data from eleven sublines indicated a higher prevalence of ancestral SVs, shared by all sublines, compared to subline-specific SVs, representing later events. Notably, the individual sublines showed a higher rate of gene disruption by SVs, hinting at potential functional selection. Our analysis further revealed that SVs common to all sublines are linked with genes in key cell growth pathways, such as Rap1, Hippo, and calcium signaling pathways. In contrast, subline-specific SVs primarily affect genes involved in neurophysiological pathways, such as glutamatergic synapse and morphine addiction pathways. These findings suggest that different genes, associated with various pathways, are disrupted at distinct stages of melanoma progression, providing insights into the genetic factors that may predispose individual melanocytes to melanomagenesis. This methodology presents a comprehensive tool for characterizing tumor genomes and understanding their relationship with disease progression and therapy resistance. We are continuing our analysis to map SVs across the entire mutation-based phylogeny of all sublines, which will further our understanding of melanoma’s genomic landscape. Citation Format: Xiwen Cui, Ayse G. Keskus, Farid R. Mehrabadi, Salem Malikic, Mikhail Kolmogorov, Chi-Ping Day, Glenn Merlino, S. Cenk Sahinalp. Structural variant dynamics in melanoma: Unraveling tumor heterogeneity and evolution [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6924.

Current understanding of Bordetella-induced cough.

Typical pathogenic bacteria of the genus Bordetella cause respiratory diseases, many of which are characterized by severe coughing in host animals. In human infections with these bacteria, such as whooping cough, coughing imposes a heavy burden on patients. The pathophysiology of this severe coughing had long been uncharacterized because convenient animal models that reproduce Bordetella-induced cough have not been available. However, rat and mouse models were recently shown as useful for understanding, at least partially, the causative factors and the mechanism of Bordetella-induced cough. Many types of coughs are induced under various physiological conditions, and the neurophysiological pathways of coughing are considered to vary among animal species, including humans. However, the neurophysiological mechanisms of the coughs in different animal species have not been entirely understood, and, accordingly, the current understanding of Bordetella-induced cough is still incomplete. Nevertheless, recent research findings may open the way for the development of prophylaxis and therapeutic measures against Bordetella-induced cough.

The role of serotonin in modulating social competence in a cooperatively breeding fish

Behavioural interactions between conspecifics rely on the appreciation of social cues, which is achieved through biochemical switching of pre-existing neurophysiological pathways. Serotonin is one of the major neurotransmitters in the central nervous system responsible for the modulation of physiological and behavioural traits, in particular social behaviour. The relative importance of serotonin in modulating optimal social responses to the available social information (i.e., social competence) is yet unknown. Here we investigate how serotonin and the serotonin 1 A receptor (5-HT1A) modulate social competence in a competitive context. In the cooperatively breeding cichlid Neolamprologus pulcher, we pharmacologically manipulated the serotonin availability and 5-HT1A activity to test their effects on social behaviours during an asymmetric contest between the owner of a defended territory containing a shelter and an intruder devoid of a territory. In this contest, the adequate response by the intruders, the focal individuals in our study, is to show submissive behaviour in order to avoid eviction from the vicinity of the shelter. While the serotonin enhancer Fluoxetine did not affect the frequency of submission towards territory owners, reducing serotonin by a low dosage of 4-Chloro-DL-phenylalanine (PCPA) increased submissive behaviour. Furthermore, threat displays towards territory owners were reduced at high dosages of Fluoxetine and also at the lowest dosage of PCPA. 5-HT1A activation increased threat displays by intruders, indicating that this receptor may not be involved in regulating social competence. We conclude that serotonin, but not its receptor 5-HT1A plays an important role in the regulation of social competence.

Gender moderates the association between resting vagally mediated heart rate variability and attentional control.

Women typically exhibit weaker attentional control ability than men. Lower resting vagally mediated heart rate variability (vmHRV) is thought to reflect the poorer function of the neurophysiological pathways underlying attentional control and thus, poorer attentional control ability. However, existing findings are inconsistent regarding the relationship between vmHRV and attentional control. Gender may be an important moderator. To examine whether gender moderates the relationship between resting vmHRV and attentional control, and to provide neurophysiological evidence for elucidating gender differences in attentional control ability. Two hundred and twenty college students completed the Attentional Control Scale to evaluate their attentional control ability. Resting vmHRV was assessed during a 5 min baseline period using an electrocardiographic amplifier (ECG100C) of the Biopac MP150 physiological recorder. (1) There was no significant difference in the total scores of the Attentional Control Scale between men and women (t = 0.498, p > 0.05), but the scores of the attentional shifting dimension of women were significantly lower than those of men (t = 1.995, p < 0.05); (2) Resting vmHRV was significantly negatively correlated with attentional control in women(r = -0.233, p < 0.01), whereas the correlation was not significant in men; (3) Gender significantly moderated the relationship between resting vmHRV and attentional control (B = -3.088, 95% boot CI [-5.431, -0.745], t = -2.598, p < 0.05); (4) Among participants with lower resting vmHRV, there was no significant difference in attentional control between men and women (B = 2.284, 95% boot CI [-0.748, 5.310], p > 0.05), but among participants with higher resting vmHRV, men scored significantly higher than women in attentional control (B = -3.377, 95% boot CI [-6.406, -0.348], p < 0.05). Gender moderates the relationship between resting vmHRV and attentional control, with higher resting vmHRV in women reflecting a compensatory response to deficits in attentional control.

Touch may reduce cognitive load during assisted typing by individuals with developmental disabilities.

Many techniques have attempted to provide physical support to ease the execution of a typing task by individuals with developmental disabilities (DD). These techniques have been controversial due to concerns that the support provider's touch can influence the typed content. The most common interpretation of assisted typing as an ideomotor phenomenon has been qualified recently by studies showing that users with DD make identifiable contributions to the process. This paper suggests a neurophysiological pathway by which touch could lower the cognitive load of seated typing by people with DD. The required sensorimotor processes (stabilizing posture and planning and executing manual reaching movements) and cognitive operations (generating and transcribing linguistic material) place concurrent demands on cognitive resources, particularly executive function (EF). A range of developmental disabilities are characterized by deficits in sensorimotor and EF capacity. As light touch has been shown to facilitate postural coordination, it is proposed that a facilitator's touch could assist the seated typist with sensorimotor and EF deficits by reducing their sensorimotor workload and thereby freeing up shared cognitive resources for the linguistic elements of the task. This is the first theoretical framework for understanding how a facilitator's touch may assist individuals with DD to contribute linguistic content during touch-assisted typing.

Interactions between environmental sensitivity and gut microbiota are associated with biomarkers of stress-related psychiatric symptoms

BackgroundHumans vary in their sensitivity to stressful and supportive environments and experiences. Such individual differences in environmental sensitivity are associated with mechanisms of stress-related psychiatric symptoms. In recent years, researchers have focused on bidirectional interactions in the brain-gut-microbiota axis as a neurophysiological pathway contributing to the mechanisms of stress-related psychiatric symptoms, and evidence is rapidly accumulating. MethodsData on environmental sensitivity, gut microbiota, gut permeability (lipopolysaccharide-binding protein; LBP) and inflammation (C-reactive protein; CRP) were collected from 90 adults (50 % female; Mage = 42.1; SDage = 10.0). Environmental sensitivity was measured using a self-report questionnaire. Study participants' feces were analyzed, and observed operational taxonomic units for richness, Shannon's index for evenness, and phylogenetic diversity for biodiversity were evaluated as indicators of gut microbiota. In addition, participants' serum was analyzed for CRP and LBP. We investigated whether the interaction between environmental sensitivity and gut microbiota is associated with biomarkers of inflammation and gut permeability. ResultsThe interaction between environmental sensitivity and gut microbiota (excluding the Shannon's index) explained the levels of these biomarkers. Individuals with high environmental sensitivity displayed higher levels of CRP and LBP, when the richness and diversity of the gut microbiota was low. However, even highly susceptible individuals had lower levels of CRP and LBP, when the richness and diversity of the gut microbiota was high. ConclusionsOur study indicates that high environmental sensitivity can be a risk factor for inflammation and gut permeability, when the gut microbiota diversity is low, suggesting a brain-gut-microbiota axis interaction.

Effects of Kisspeptin on Sexual Brain Processing and Penile Tumescence in Men With Hypoactive Sexual Desire Disorder

The human physiological sexual response is crucial for reward, satisfaction, and reproduction. Disruption of the associated neurophysiological pathways predisposes to low sexual desire; the most prevalent psychological form is hypoactive sexual desire disorder (HSDD), which affects 8% of men but currently has no effective pharmacological treatment options. The reproductive neuropeptide kisspeptin offers a putative therapeutic target, owing to emerging understanding of its role in reproductive behavior. To determine the physiological, behavioral, neural, and hormonal effects of kisspeptin administration in men with HSDD. This double-blind, 2-way crossover, placebo-controlled randomized clinical trial was performed at a single academic research center in the UK. Eligible participants were right-handed heterosexual men with HSDD. Physiological, behavioral, functional magnetic resonance imaging (fMRI), and hormonal analyses were used to investigate the clinical and mechanistic effects of kisspeptin administration in response to visual sexual stimuli (short and long video tasks). The trial was conducted between January 11 and September 15, 2021, and data analysis was performed between October and November 2021. Participants attended 2 study visits at least 7 days apart, in balanced random order, for intravenous infusion of kisspeptin-54 (1 nmol/kg/h) for 75 minutes or for administration of a rate-matched placebo. Changes in (1) brain activity on whole-brain analysis, as determined by fMRI blood oxygen level-dependent activity in response to visual sexual stimuli during kisspeptin administration compared with placebo, (2) physiological sexual arousal (penile tumescence), and (3) behavioral measures of sexual desire and arousal. Of the 37 men randomized, 32 completed the trial. Participants had a mean (SD) age of 37.9 (8.6) years and a mean (SD) body mass index of 24.9 (5.4). On viewing sexual videos, kisspeptin significantly modulated brain activity in key structures of the sexual-processing network on whole-brain analysis compared with placebo (mean absolute change [Cohen d] = 0.81 [95% CI, 0.41-1.21]; P = .003). Furthermore, improvements in several secondary analyses were observed, including significant increases in penile tumescence in response to sexual stimuli (by up to 56% more than placebo; mean difference = 0.28 units [95% CI, 0.04-0.52 units]; P = .02) and behavioral measures of sexual desire-most notably, increased happiness about sex (mean difference = 0.63 points [95% CI, 0.10-1.15 points]; P = .02). Collectively, this randomized clinical trial provides the first evidence to date showing that kisspeptin administration substantially modulates sexual brain processing in men with HSDD, with associated increases in penile tumescence and behavioral measures of sexual desire and arousal. These data suggest that kisspeptin has potential as the first pharmacological treatment for men with low sexual desire. isrctn.org Identifier: ISRCTN17271094.

Psychiatric Psychobiological Treatment Versus Exclusive Psychological Treatment in Depressive Disorders

Introduction: Scientific information on the antidepressant effectiveness of the varied usual therapeutic interventions is considerable but of poor quality. Objective: To analyse the scientifically well qualified international contributions on the effectiveness of habitual psychobiological psychiatric interventions in depressive disorders. Method: N= 6 structured bibliographic systems have been reviewed in a non-systematic, narrative and synthetic way and N= 75 significant contributions have been selected. Results and discussion: Patients with severe depression are more likely to receive any type of medical attention, but less likely to receive adequate attention. The use of both drugs and psychotherapy is the habitual mixed combined intervention during any ordinary psychiatric treatment. We will call it psychobiological or psychopharmacological intervention. The exclusive psychological intervention without using any medically prescribed drugs, is likely to be less cost/effective. The matter is not only to prioritise but also to adequately combine psychiatric interventions and added psychological interventions when convenient. The intervention on the neurophysiological pathways related with glutamate, the GABAergic, opioidergic, and inflammatory systems as well as on connectome and microbiome are being promoted for future drug antidepressant therapy with encouraging results. Conclusion: The mixed psychiatric option using drugs and psychotherapy, either regulated or not, by the intervening psychiatrist himself or herself is probably the main therapeutic choice for the correctly diagnosed depressive disorders. The psychotherapeutics intervention excluding the psychobiological psychiatric intervention in correctly diagnosed depressions will be insufficient in general. The professional psychological intervention may obviously complement the mixed psychiatric intervention, but can not replace it.

Infection with an acanthocephalan helminth reduces anxiety-like behaviour in crustacean host

Trophically transmitted heteroxenous parasites of diverse clades can decrease or reverse antipredator behaviours in their intermediate hosts, thereby increasing their chances of reaching their final hosts. Such behavioural alterations could result from compromised cognitive abilities affecting fear- or more generally stress-related neurophysiological pathways. We tested this hypothesis in a key model system in the study of parasitic manipulation, the fish acanthocephalan parasite Pomphorhynchus tereticollis and its intermediate crustacean host Gammarus fossarum, using the ‘threat of electric shock’ paradigm. We exposed uninfected and infected G. fossarum to chronic and/or acute electric shock programs at two different intensities (voltage), and then quantified their sheltering behaviour as a proxy for anxiety-like state. Infected gammarids did not express anxiety-like response to electric shocks, while uninfected gammarids hid more when exposed to acute treatments, and when exposed to the high intensity chronic treatment. Interestingly, the lack of response in infected gammarids depended on parasite developmental stage. Our results support the hypothesis that this acanthocephalan parasite impacts the general anxiety-like circuitry of their intermediate host. Further studies are needed to investigate whether it involves inappropriate processing of information, impaired integration, or altered activation of downstream pathways initiating behavioural action.

The vital role of arcuate nociceptin/orphanin FQ neurones in mounting an oestradiol-dependent adaptive response to negative energy balance via inhibition of nearby proopiomelanocortin neurones.

We tested the hypothesis that N/OFQ neurones in the arcuate nucleus (N/OFQARC ) inhibit proopiomelanocortin (POMCARC ) neurones in a diet- and hormone-dependent manner to promote a more extensive rebound hyperphagia upon re-feeding following an 18h fast. We utilized intact male or ovariectomized (OVX) female mice subjected to ad libitum-feeding or fasting conditions. N/OFQARC neurones under negative energy balance conditions displayed heightened sensitivity as evidenced by a decreased rheobase threshold, increased firing frequency, and increased burst duration and frequency compared to ad libitum-feeding conditions. Stimulation of N/OFQARC neurones more robustly inhibited POMCARC neurones under fasting conditions compared to ad libitum-feeding conditions. N/OFQARC inhibition of POMCARC neurones is hormone dependent as chemostimulation of N/OFQARC neurones from fasted males and OVX females produced a sizable outward current in POMCARC neurones. Oestradiol (E2 ) markedly attenuated the N/OFQ-induced POMCARC outward current. Additionally, N/OFQ tonically inhibits POMCARC neurones to a greater degree under fasting conditions than in ad libitum-feeding conditions as evidenced by the abrogation of N/OFQ-nociceptin opioid peptide (NOP) receptor signalling and inhibition of N/OFQ release via chemoinhibition of N/OFQARC neurones. Intra-arcuate nucleus application of N/OFQ further elevated the hyperphagic response and increased meal size during the 6 h re-feed period, and these effects were mimicked by chemostimulation of N/OFQARC neurones in vivo. E2 attenuated the robust N/OFQ-induced rebound hyperphagia seen in vehicle-treated OVX females. These data demonstrate that N/OFQARC neurones play a vital role in mitigating the impact of negative energy balance by inhibiting the excitability of anorexigenic neural substrates, an effect that is diminished by E2 in females. KEY POINTS: Nociceptin/orphanin FQ (N/OFQ) promotes increased energy intake and decreased energy expenditure under conditions of positive energy balance in a sex- and hormone-dependent manner. Here it is shown that under conditions of negative energy balance, i.e. fasting, N/OFQ inhibits anorexigenic proopiomelanocortin (POMC) neurones to a greater degree compared to homeostatic conditions due to fasting-induced hyperexcitability of N/OFQ neurones. Additionally, N/OFQ promotes a sustained increase in rebound hyperphagia and increase in meal size during the re-feed period following a fast. These results promote greater understanding of how energy balance influences the anorexigenic circuitry of the hypothalamus, and aid in understanding the neurophysiological pathways implicated in eating disorders promoting cachexia.

Can exercise attenuate the negative effects of long COVID syndrome on brain health?

The impetus for many governments globally to treat the novel coronavirus (COVID-19) as an endemic warrant more research into the prevention, and management of long COVID syndrome (LCS). Whilst the data on LCS remains scarce, reports suggest a large proportion of recovered individuals will experience ongoing neuropsychological symptoms, even with mild disease severity. The pathophysiology underlying LCS is multifaceted. Evidence suggests that altered inflammatory, neurotrophic, and neurotransmitter pathways within the brain contribute to neuropsychological symptoms reported following COVID-19. Exercise or regular physical activity has long been shown to have positive effects on brain health and cognition through exerting positive effects on inflammatory markers, neurotransmitters, and neurotropic factors analogous to the neurophysiological pathways proposed to be disrupted by COVID-19 infection. Thus, exercise may serve as an important lifestyle behavior in the management of LCS. In this opinion article, we present the evidence to support the positive role of exercise in the management of cognitive symptom that manifest with LCS and discuss important considerations and interactions with cardiorespiratory and exercise tolerance complications that often present for individuals experiencing LCS. We highlight the need for more research and training of sports medicine practitioners and clinical exercise physiologists in the management of LCS with exercise and call for further research to understand the optimal dose-responses and exercise prescription guidelines for cognitive benefits and minimizing other complications.

The Current View on the Paradox of Pain in Autism Spectrum Disorders.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder, which affects 1 in 44 children and may cause severe disabilities. Besides socio-communicational difficulties and repetitive behaviors, ASD also presents as atypical sensorimotor function and pain reactivity. While chronic pain is a frequent co-morbidity in autism, pain management in this population is often insufficient because of difficulties in pain evaluation, worsening their prognosis and perhaps driving higher mortality rates. Previous observations have tended to oversimplify the experience of pain in autism as being insensitive to painful stimuli. Various findings in the past 15 years have challenged and complicated this dogma. However, a relatively small number of studies investigates the physiological correlates of pain reactivity in ASD. We explore the possibility that atypical pain perception in people with ASD is mediated by alterations in pain perception, transmission, expression and modulation, and through interactions between these processes. These complex interactions may account for the great variability and sometimes contradictory findings from the studies. A growing body of evidence is challenging the idea of alterations in pain processing in ASD due to a single factor, and calls for an integrative view. We propose a model of the pain cycle that includes the interplay between the molecular and neurophysiological pathways of pain processing and it conscious appraisal that may interfere with pain reactivity and coping in autism. The role of social factors in pain-induced response is also discussed. Pain assessment in clinical care is mostly based on subjective rather than objective measures. This review clarifies the strong need for a consistent methodology, and describes innovative tools to cope with the heterogeneity of pain expression in ASD, enabling individualized assessment. Multiple measures, including self-reporting, informant reporting, clinician-assessed, and purely physiological metrics may provide more consistent results. An integrative view on the regulation of the pain cycle offers a more robust framework to characterize the experience of pain in autism.

A feasibility study on yoga’s mechanism of action for chronic low back pain: psychological and neurophysiological changes, including global gene expression and DNA methylation, following a yoga intervention for chronic low back pain

IntroductionYoga has been shown to reduce pain and improve function in populations with chronic low back pain (cLBP), yet the underlying molecular mechanisms remain elusive. This study examined the feasibility and acceptability of a yoga research protocol, including recruitment, retention, and data collection, and investigated the preliminary effects of yoga on psychological and neurophysiological functions, including gene expression and DNA methylation profiles, in participants with cLBP.MethodsA one-arm trial was conducted with 11 participants with cLBP who enrolled in a 12-week yoga intervention. Data on subjective pain characteristics, quantitative sensory testing, and blood for analysis of differentially expressed genes and CpG methylation was collected prior to the start of the intervention and at study completion.ResultsBased on pre-determined feasibility and acceptability criteria, the yoga intervention was found to be feasible and highly acceptable to participants. There was a reduction in pain severity, interference, and mechanical pain sensitivity post-yoga and an increase in emotion regulation and self-efficacy. No adverse reactions were reported. Differential expression analysis demonstrated that the yoga intervention induced increased expression of antisense genes, some of which serve as antisense to known pain genes. In addition, there were 33 differentially hypomethylated positions after yoga (log2 fold change ≥ 1), with enrichment of genes involved in NIK/NF-kB signaling, a major pathway that modulates immune function and inflammation.Discussion/conclusionsThe study supports the feasibility and acceptability of the proposed protocol to test a specific mechanism of action for yoga in individuals with cLBP. These results also support the notion that yoga may operate through our identified psychological and neurophysiologic pathways to influence reduced pain severity and interference.

Associations between apathy and comprehensive frailty as assessed by the Kihon Checklist among community-dwelling Japanese older adults.

Frailty is a multidimensional condition characterised by reduced physical and psychological resilience. Older adults also frequently demonstrate apathy, suggesting that it shares similar neuro-physiological pathways with frailty. This cross-sectional study aimed to investigate the association between apathy and frailty as defined by a comprehensive assessment. We analyzed 882 older adults (mean age: 74.4 ± 6.4 years; 62.1% female) who participated in a community-based health check survey (Tarumizu Study). Apathy was measured by the Geriatric Depression Scale-3A, a three-item subset of the Geriatric Depression Scale-15, and frailty by the Kihon Checklist of physical, psychological, functional, and social status. Associations were examined by multinomial logistic regression with frailty status (robust, pre-frailty, frailty) as the dependent variable, apathy as the independent variable, and sociodemographic factors, medications, cognitive function, functional capacity, and mood symptoms as potential confounders. Apathy was observed in 23.7% of individuals, and logistic regression revealed significant associations with both pre-frailty and frailty after confounder adjustment (pre-frailty: odds ratio (OR) 1.80, 95% CI 1.22-2.64; frailty: OR 3.24, 95% CI 1.63-6.42). Participants with apathy also exhibited greater deficits in the Kihon Checklist subdomains instrumental activities of daily living (P=0.022), physical function (P < 0.001), oral function (P < 0.001), and cognitive function (P=0.001). Our findings underscore the importance of comprehensive frailty assessment and demonstrate that apathy can have pervasive deleterious effects on geriatric health.

A Comprehensive Review of Pain Interference on Postural Control: From Experimental to Chronic Pain.

Motor control, movement impairment, and postural control recovery targeted in rehabilitation could be affected by pain. The main objective of this comprehensive review is to provide a synthesis of the effect of experimental and chronic pain on postural control throughout the available literature. After presenting the neurophysiological pathways of pain, we demonstrated that pain, preferentially localized in the lower back or in the leg induced postural control alteration. Although proprioceptive and cortical excitability seem modified with pain, spinal modulation assessment might provide a new understanding of the pain phenomenon related to postural control. The literature highlights that the motor control of trunk muscles in patient presenting with lower back pain could be dichotomized in two populations, where the first over-activates the trunk muscles, and the second under-activates the trunk muscles; both generate an increase in tissue loading. Taking all these findings into account will help clinician to provide adapted treatment for managing both pain and postural control.

Rabies Virus Exploits Cytoskeleton Network to Cause Early Disease Progression and Cellular Dysfunction.

Rabies virus (RABV) is a cunning neurotropic pathogen and causes top priority neglected tropical diseases in the developing world. The genome of RABV consists of nucleoprotein (N), phosphoprotein (P), matrix protein (M), glycoprotein (G), and RNA polymerase L protein (L), respectively. The virus causes neuronal dysfunction instead of neuronal cell death by deregulating the polymerization of the actin and microtubule cytoskeleton and subverts the associated binding and motor proteins for efficient viral progression. These binding proteins mainly maintain neuronal structure, morphology, synaptic integrity, and complex neurophysiological pathways. However, much of the exact mechanism of the viral-cytoskeleton interaction is yet unclear because several binding proteins of the actin-microtubule cytoskeleton are involved in multifaceted pathways to influence the retrograde and anterograde axonal transport of RABV. In this review, all the available scientific results regarding cytoskeleton elements and their possible interactions with RABV have been collected through systematic methodology, and thereby interpreted to explain sneaky features of RABV. The aim is to envisage the pathogenesis of RABV to understand further steps of RABV progression inside the cells. RABV interacts in a number of ways with the cell cytoskeleton to produce degenerative changes in the biochemical and neuropathological trails of neurons and other cell types. Briefly, RABV changes the gene expression of essential cytoskeleton related proteins, depolymerizes actin and microtubules, coordinates the synthesis of inclusion bodies, manipulates microtubules and associated motors proteins, and uses actin for clathrin-mediated entry in different cells. Most importantly, the P is the most intricate protein of RABV that performs complex functions. It artfully operates the dynein motor protein along the tracks of microtubules to assist the replication, transcription, and transport of RABV until its egress from the cell. New remedial insights at subcellular levels are needed to counteract the destabilization of the cytoskeleton under RABV infection to stop its life cycle.

Actualización en el tratamiento de la neurodegeneración en las enfermedades lisosomales

Lysosomal diseases are a set of rare diseases where the genetic deficiency of certain enzymes gives rise to the accumulation of substrates at the multi-organ level. The treatment of these inborn errors of metabolism is still under continuous investigation since when they exist, they present limitations trying to increase the synthesis of the enzyme or decrease the deposit of substrate, without reaching the definitive solution, and therefore a cure. The progressive and limiting neurodegeneration that most of them produce from pediatric ages, is one of the greatest challenges. Hematopoietic cell transplantation and enzyme replacement therapy are accepted treatments for some of these diseases; however,its results on the control and progression of neurological symptoms often remain disappointing. Undoubtedly, crossing the blood-brain barrier is one of the obstacles that many clinical trials currently underway aim to overcome. Gene therapy and neurophysiological pathways triggered by the lack of partial or total degradation of molecules also constitute a new avenue of study whose main objective is also based on preventing progression in the deterioration of cognitive function. Therefore, the objective of this work is to carry out a review to know the approved therapies and the lines of research in progress in relation to the neurodegeneration of lysosomal diseases and It is essential to continue advancing in this field with further development of these approaches and the search new perspectives on therapies that can have a great impact on the quality of life of these patients.