Neurophysiological Pathways Research Articles

Nociceptive pain and anxiety in equines: Physiological and behavioral alterations.

Pain and anxiety are two of the most important concerns in clinical veterinary medicine because they arise as consequences of multiple factors that can severely affect animal welfare. The aim of the present review was to provide a description and interpretation of the physiological and behavioral alterations associated with pain and anxiety in equines. To this end, we conducted an extensive review of diverse sources on the topic. The article begins by describing the neurophysiological pathway of pain, followed by a discussion of the importance of the limbic system in responses to pain and anxiety, since prolonged exposure to situations that cause stress and pain generates such physiological changes as tachycardia, tachypnea, hypertension, hyperthermia, and heart rate variability (HRV), often accompanied by altered emotional states, deficient rest, and even aggressiveness. In the long term, animals may show deficiencies in their ability to deal with changes in the environment due to alterations in the functioning of their immune, nervous, and endocrinologic systems. In conclusion, pain and anxiety directly impact the homeostasis of organisms, so it is necessary to conduct objective evaluations of both sensations using behavioral scales, like the horse grimace scale, complemented by assessments of blood biomarkers to analyze their correlation with physiological parameters: Heart rate, respiratory rate, HRV, theparasympathetic tone activity index, lactate and glucose levels, and temperature. Additional tools – infrared thermography, for example – can also be used in these efforts to improve the quality of life and welfare of horses.

Oxygen Metabolism-induced Stress Response Underlies Heart-brain Interaction Governing Human Consciousness-breaking and Attention.

Neuroscientists have emphasized visceral influences on consciousness and attention, but the potential neurophysiological pathways remain under exploration. Here, we found two neurophysiological pathways of heart-brain interaction based on the relationship between oxygen-transport by red blood cells (RBCs) and consciousness/attention. To this end, we collected a dataset based on the routine physical examination, the breaking continuous flash suppression (b-CFS) paradigm, and an attention network test (ANT) in 140 immigrants under the hypoxic Tibetan environment. We combined electroencephalography and multilevel mediation analysis to investigate the relationship between RBC properties and consciousness/attention. The results showed that RBC function, via two independent neurophysiological pathways, not only triggered interoceptive re-representations in the insula and awareness connected to orienting attention but also induced an immune response corresponding to consciousness and executive control. Importantly, consciousness played a fundamental role in executive function which might be associated with the level of perceived stress. These results indicated the important role of oxygen-transport in heart-brain interactions, in which the related stress response affected consciousness and executive control. The findings provide new insights into the neurophysiological schema of heart-brain interactions.

Pharmacological drug strategies in Alzheimer's Disease

Introduction. Alzheimer's disease (AD) is a neurodegenerative disorder with a poor prognosis and no cure that affects millions of people worldwide. Medicines today in clinical studies try to investigate possible therapeutic effects that progress or stop the disease. Objective. This review is necessary to create a current panorama in 2021, describing the main pathways under study to inhibit important pathways of disease progression, such as pathways cholinergic system and ROCK inhibitors, as well as new perspectives of treatment with possible combination of drugs, to decrease neuroinflammation and change the course of the disease. Method. Reviewed ClinicalTrials.gov as of January 19, 2021, identified all trials of pharmacologic agents currently being developed for treatment of AD in phase 3 of clinical study, thus obtaining a global panorama to curb this devastating disease, creating better perspectives on the treatment of AD. Results. Different drugs (n = 25) were divided by types of targets of neurophysiological pathways (amyloid inhibitor; tau inhibitor; neurotransmitter receptors; non-steroidal anti-inflammatory drugs (NSAIDs), mitochondria and metabolic functions; synaptic plasticity). Conclusions. Advances in clinical trials bring hope and new avenues as targets for AD treatment are encouraged and show promise for new lines of treatment. New studies with more therapeutic combinations that change the course of the disease should be encouraged.

Proteomic Characterization of the Dynamics of Ischemic Stroke in Mice.

Novel therapies and biomarkers are needed for the treatment of acute ischemic stroke (AIS). This study aimed to provide comprehensive insights into the dynamic proteome changes and underlying molecular mechanisms post-ischemic stroke. TMT-coupled proteomic analysis was conducted on mouse brain cortex tissue from five time points up to 4 weeks poststroke in the distal hypoxic-middle cerebral artery occlusion (DH-MCAO) model. We found that nearly half of the detected proteome was altered following stroke, but only ∼8.6% of the changes were at relatively large scales. Clustering on the changed proteome defined four distinct expression patterns characterized by temporal and quantitative changes in innate and adaptive immune response pathways and cytoskeletal and neuronal remodeling. Further analysis on a subset of 309 “top hits”, which temporally responded to stroke with relatively large and sustained changes, revealed that they were mostly secreted proteins, highly correlated to different cortical cytokines, and thereby potential pharmacodynamic biomarker candidates for inflammation-targeting therapies. Closer examination of the top enriched neurophysiologic pathways identified 57 proteins potentially associated with poststroke recovery. Altogether, our study generated a rich dataset with candidate proteins worthy of further validation as biomarkers and/or therapeutic targets for stroke. The proteomics data are available in the PRIDE Archive with identifier PXD025077.

Adverse health effects of PCBs on fine motor performance – Analysis of a neurophysiological pathway in the HELPcB surveillance program

Since research literature indicates neurotoxic health effects of polychlorinated biphenyls (PCBs), it is necessary to identify by which mechanism PCBs might affect the human central nervous system and human behavior. In the present study, a neurophysiological pathway is assumed to explain the negative association of PCB exposure and performance in fine motor tasks mediated by the level of the dopamine (DA) metabolite homovanillic acid (HVA). A total of 113 occupationally PCB exposed workers and their relatives from an occupational health monitoring program were examined (89.4 % men). PCBs were analyzed in plasma via human biomonitoring and HVA was assessed in urine. The motor performance series was used to measure two dimensions of fine motor skills with 5 subgroups (accuracy: steadiness, line tracking accuracy; speed: line tracking speed, aiming, tapping). The direct effects of PCBs on fine motor performance and the indirect effects of PCBs on fine motor performance via DA metabolite HVA were tested with multiple regressions. We found significant effects for the accuracy dimension, namely a negative direct effect of PCBs on line tracking accuracy mediated by HVA. Further, an indirect effect could be found for PCBs with steadiness accuracy through HVA. There were no significant effects related to fine motor performances in the speed dimension. These results provide first indications for an underlying neurochemical pathomechanism involving the dopamine system of PCB-related deterioration of fine motor performance regarding accuracy.

The Feeling Voice: A Linklater Approach to Freeing the Voice through Embodied Connection to Image

The neuro-physiological pathways connecting words with the sensory apparatus of the body and with nature have not disappeared, but they have been short-circuited as the technology of communication ...

Changes in pain sensitivity and spinal stiffness in relation to responder status following spinal manipulative therapy in chronic low Back pain: a secondary explorative analysis of a randomized trial

BackgroundIn a prior randomized trial, we demonstrated that participants receiving spinal manipulative therapy at a pain-sensitive segment instead of a stiff segment experienced increased mechanical pressure pain thresholds. We hypothesized that the targeted segment mediated this increase through a segment-dependent neurophysiological reflective pathway. Presently, it is not known if this decrease in pain sensitivity is associated with clinical improvement. Therefore, we performed an explorative analysis to examine if changes in experimental pain sensitivity (mechanical and thermal) and lumbar stiffness were further dependent on clinical improvement in disability and patient-reported low back pain.MethodsThis study is a secondary explorative analysis of data from the randomized trial that compared 132 participants with chronic low back pain who received lumbar spinal manipulative therapy applied at either i) the stiffest segment or ii) the segment having the lowest pain threshold (i.e., the most pain-sensitive segment). We collected data at baseline, after the fourth session of spinal manipulation, and at 14-days follow-up. Participants were dichotomized into responders/non-responders using different clinical variables (disability and patient-reported low back pain) with varying threshold values (0, 30, and 50% improvement). Mixed models were used to assess changes in experimental outcomes (stiffness and pain sensitivity). The fixed interaction terms were time, segment allocation, and responder status.ResultsWe observed a significant increase in mechanical pressure pain thresholds for the group, which received spinal manipulative therapy at the most pain-sensitive segment independent of whether they improved clinically or not. Those who received spinal manipulation at the stiffest segment also demonstrated increased mechanical pain sensitivity, but only in the subgroup with clinical improvement. We did not observe any changes in lumbar stiffness.ConclusionOur results suggest the existence of two different mechanistic pathways associated with the spinal manipulation target. i) A decrease of mechanical pain sensitivity independent of clinical outcome (neurophysiological) and ii) a decrease as a reflection of the clinical outcome. Together, these observations may provide a novel framework that improves our understanding of why some respond to spinal manipulative therapy while others do not.Trial registrationClinicalTrials.gov identifier: NCT04086667 registered retrospectively September 11th 2019.

The Role of Affectionate Caregiver Touch in Early Neurodevelopment and Parent-Infant Interactional Synchrony.

Though rarely included in studies of parent–infant interactions, affectionate touch plays a unique and vital role in infant development. Previous studies in human and rodent models have established that early and consistent affectionate touch from a caregiver confers wide-ranging and holistic benefits for infant psychosocial and neurophysiological development. We begin with an introduction to the neurophysiological pathways for the positive effects of touch. Then, we provide a brief review of how affectionate touch tunes the development of infant somatosensory, autonomic (stress regulation), and immune systems. Affective touch also plays a foundational role in the establishment of social affiliative bonds and early psychosocial behavior. These touch-related bonding effects are known to be mediated primarily by the oxytocin system, but touch also activates mesocorticolimbic dopamine and endogenous opioid systems which aid the development of social cognitive processes such as social learning and reward processing. We conclude by proposing a unique role for affectionate touch as an essential pathway to establishing and maintaining parent-infant interactional synchrony at behavioral and neural levels. The limitations of the current understanding of affectionate touch in infant development point to fruitful avenues for future research.

Neurophysiology of cognitive behavioural therapy, deep breathing and progressive muscle relaxation used in conjunction with ART treatments: a narrative review.

Infertility is defined as the failure to achieve clinical pregnancy after 12 months of regular unprotected intercourse. It could be due to male or female factors, each requiring different treatment options. ART treatment exposes couples to numerous psychological stressors. Therefore, it has been recommended by the ESHRE Psychology and Counselling Guideline Development Group recently that psychosocial support should be offered as a complementary therapy during infertility treatments. In this context, the efficiency of different psychological interventions, such as cognitive behaviour therapy (CBT), deep breathing (DB), and progressive muscle relaxation (PMR), was evaluated in several clinical trials in terms of couples' mental health and pregnancy outcomes. The neurophysiology of CBT, DB and PMR, which are used in interventional studies, in both men and women undergoing ART, has not yet been fully elucidated. This review represents a comprehensive report, aiming to collate novel insights into the neurobiological processes and physiological mechanisms that occur during the practice of CBT, DB and PMR. PubMed, Google Scholar and Cochrane Library were interrogated to conduct this comprehensive literature review. The search was carried out using combinations of MeSH terms and keywords: infertility, assisted reproductive techniques, IVF, ICSI, emotions, psychological stress, cognitive behavioural therapy, mind-body therapies and relaxation. Relevant information related to the mechanism of action of stress management techniques were obtained from original articles and reviews published in English without taking into consideration the time of publication. Moreover, as it was not the major focus of the review, only recent systematic reviews (2015-2019) pinpointing the effects of psychological interventions on infertility treatment outcomes were also retrieved from the above-mentioned databases. CBT, DB and PMR may modify the activity of stress-related brain regions such as the prefrontal cortex, amygdala, hypothalamus and hippocampus, as demonstrated by functional MRI and electroencephalogram studies. Furthermore, applying these techniques was associated with mood improvements and a decline in stress biomarkers, and, hypothetically, reducing stress biomarkers attenuates the stress-induced effects on ART outcomes. Increasing the knowledge of fertility staff, researchers and physicians regarding the mechanisms of action of these stress management techniques has several advantages. For instance, understanding the underlying neurophysiological pathways would assist practitioners to engage ART couples in the practice of these techniques. Also, it may enhance the quality of the support programmes and psychological research. Accordingly, this will ensure that these interventions reach their full potential and therefore improve clinical outcomes.

Proprioceptive Feedback from AMI Amputation Modulates Cortical and Subcortical Reorganization

Maladaptive cerebral neuroplasticity is a well-established consequence of limb amputation. However, little is known about the potentially causal role of neuromuscular feedback in preserving the cortical and subcortical structures essential for sensation and motor planning, or modulating phantom limb sensation and pain. In this investigation, we study the impact of the agonist-antagonist myoneural interface (AMI) amputation procedure, which preserves proprioceptive neuromuscular feedback, on subcortical and cortical reorganization. We perform neuroimaging on subjects with AMI amputation (AA, n = 10), traditional amputation (TA, n = 10) and no amputation (NA, controls, n = 10). While TAs demonstrate diminished subcortical gray matter volume in the pallidum, accumbens and thalamus (p < 0.05) as compared to NAs, AAs had no significant changes when compared to NAs (p < 0.05). Cortical thickness of Broadmann area 3a and 3b were also significantly increased in TAs, but remained unchanged in AAs, as compared to NAs (p < 0.05). Further, we find phantom limb sensation to be significantly correlated with the reorganization of the accumbens, thalamus, Broadmann area 3a and 3b, suggesting a potential mechanistic linkage to sensorimotor reorganization. The AMI amputation, by preserving afferent proprioceptive feedback, may minimize reorganization and promote conventional sensorimotor neurophysiological pathways.

Experimental effects of acute exercise on forgetting.

Prior research has evaluated the effects of acute exercise on episodic memory function. These studies have, on occasion, demonstrated that acute exercise may enhance both short- and long-term memory. It is uncertain as to whether the acute exercise improvements in long-term memory are a result of acute exercise attenuating declines in long-term memory, or rather, are driven by the enhancement effects of acute exercise on short-term memory. The present empirical study evaluates whether the decline from short- to long-term is influenced by acute exercise. This relationship is plausible as exercise has been shown to activate neurophysiological pathways (e.g., RAC1) that are involved in the mechanisms of forgetting. To evaluate the effects of acute exercise on forgetting, we used data from 12 of our laboratory's prior experiments (N = 538). Across these 12 experiments, acute exercise ranged from 10 to 15 mins in duration (moderate-to-vigorous intensity). Episodic memory was assessed from word-list or paragraph-based assessments. Short-term memory was assessed immediately after encoding, with long-term memory assessed approximately 20-min later. Forgetting was calculated as the difference in short- and long-term memory performance. Acute exercise (vs. seated control) was not associated with an attenuated forgetting effect (d = 0.10; 95% CI: -0.04, 0.25, P = 0.17). We observed no evidence of a significant moderation effect (Q = 6.16, df = 17, P = 0.17, I2 = 0.00) for any of the evaluated parameters, including study design, exercise intensity and delay period. Across our 12 experimental studies, acute exercise was not associated with an attenuated forgetting effect. We discuss these implications for future research that evaluates the effects of acute exercise on long-term memory function.

A timeline of female stress urinary incontinence: how technology defined theory and advanced treatment.

Prevailing theories and treatments of female stress urinary incontinence are built on 120 years of evolution in understanding the structure and function of the female bladder neck and urethra and of considering why treatments failed. In our management of patients, it is important to understand and appreciate how our management of female stress urinary incontinence has evolved and which treatments have prevailed as we advance our knowledge for future treatments. The purpose of this review is to describe how advances in technology impacted and shaped prevailing theories or understanding of the pathophysiology of stress urinary incontinence and influences our treatment approach. An extensive literature search was performed from 1900 to present identifying articles that discussed technological advancements in female urology, theories of female stress incontinence, and treatments. The literature from the 20th century to the present shows a nonlinear evolution of the pathophysiological mechanism of stress urinary incontinence (SUI) from a notion of SUI and secondary to a simple anatomic finding to consideration of the effects of neurophysiologic pathways on SUI. Slings, however, have been a staple in the management of SUI. The pubovaginal sling (PVS) is a procedure that, with minor modifications (graft size, suture preference) has withstood the test of time and maintained its place in the armamentarium of SUI treatment for 100 years. It is therefore imperative that we continue to educate our residents and fellows on the surgical techniques and indications for use of the PVS.

Sex moderates the relationship between resting heart rate variability and self-reported difficulties in emotion regulation.

Lower resting vagally mediated heart rate variability (HRV) is thought to reflect poorer function of the neurophysiological pathways underlying emotion regulation (ER) and thus, poorer ER abilities. Sex differences in resting HRV exists such that women typically exhibit higher resting HRV than men. It is proposed that greater HRV in women reflects compensation for greater negative affect such as anxiety and depression. However, research has not yet investigated how the association between resting HRV and every day perceived difficulties in ER may be moderated by sex. The current study sought to test this in a sample of 362 young participants (207 females, mean age of 19). Resting HRV was assessed during a 5-min baseline period using an electrocardiogram. Participants then completed the 36-item Difficulties in Emotion Regulation Scale (DERS) designed to evaluate participant's daily difficulties in ER. Controlling for several covariates, sex significantly moderated the relationship between resting HRV and ER difficulties, such that women showed a much stronger relationship compared with men. Specifically, women with lower HRV reported greater difficulties in ER compared with men with lower HRV, whereas women with higher HRV reported slightly lesser difficulties in ER compared with all men. Overall, this study supports a deeper understanding of how neurophysiological differences in ER between men and women-as indexed by resting HRV-may contribute to how effectively individuals regulate their emotions on a day-to-day basis, with implications for well-being. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

The association between apathy and frailty in older adults: a new investigation using data from the Mapt study

Introduction Apathy is a behavioral syndrome that has been suggested to share similar neuro-physiological pathways with frailty. Objective To investigate the cross-sectional association between apathy and frailty using original data from dementia-free, community-dwelling older adults Method A cross-sectional analysis was performed to test the association between frailty (according to Fried’s frailty phenotype) and apathy (defined by three items from Geriatric Depression Scale) using data from MAPT, a 3-year, randomized, multicenter, placebo-controlled trial among community-dwelling, dementia-free participants (1.679 individuals with mean age of 75 years). Results The ordinal logistic regression showed that apathetic individuals had a two-fold more probability to be rated as frail (OR 2.20, 95% CI 1.7–2.9), when adjusting for confounders. Apathetic individuals display a two-fold more likelihood to be rated as pre-frail (RRR 2.1; 95% CI 1.5–2.8) and a three-fold higher probability to be rated as frail (RRR 3.5, 95% CI 1.8–6.9) compared to robust participants. Conclusion Although data on the associations between apathy and frailty are scarce, these conditions potentially shares physiological mechanisms and were found to be closely associated. Temporal association between frailty and apathy deserve to be further investigated.

An update on the current management of adult obstructive sleep apnoea.

Obstructive sleep apnoea (OSA) is common in adults. Various contributing factors to this condition have resulted in the development of a number of potential treatment modalities, some of which are in evolution. A multidisciplinary team involving the general practitioner is animportant aspect in providing personalised care. The aim of this review is to provide aclinical update on the recent developments and future directions inadult OSA management. In-lab polysomnography remains important in the diagnosis of OSA, although home sleep studies have good specificity and sensitivity in particular subgroups of patients. First-line therapy in adult OSA is continuous positive airway pressure, with mandibular advancement splints and surgical intervention considered second-line. Adjunctive therapies include weight loss, avoidance of supine sleep, management of nasal obstruction, alcohol intake limitation and exercise. Advancements in medications targeting multiple neurophysiological pathways, and surgical insertion of hypoglossal nerve stimulator devices represent possible future treatment pathways in Australia.

An East Meets West Approach to the Understanding of Emotion Dysregulation in Depression: From Perspective to Scientific Evidence.

Depression, an emotion regulation disorder, is a prevalent mental illness in the world. Meanwhile, traditional Chinese medicine (TCM) has been increasingly regarded as a promising and effective alternative therapy approach for patients with depression. Despite many years of research on depression, the current understanding of the pathological mechanism of depression based on TCM theories is still in its infancy. Due to the lack of scientific evidence in the past, TCM is not fully recognized by researchers around the world. This review firstly summarizes the pathogenesis and etiology of depression in terms of both Eastern and Western medical systems. Secondly, it adopts an integrated Eastern and Western approach to propose some plausible neurophysiological pathways linking the liver, spleen, and heart functions explicated in TCM theory. The aim of this theoretical review is to bridge the knowledge gap between Eastern and Western medicine, which may better explain the pathology of depression.

Heart rate variability and inflammation: A meta-analysis of human studies

The inflammatory reflex is known as the body’s primary defense against infection and has been implicated in a number of diseases. The magnitude of the inflammatory response is important, as an extreme or insufficient response can be differentially harmful to the individual. Converging evidence suggests that the autonomic nervous system (ANS) regulates the inflammatory reflex. Heart rate variability (HRV) can be separated into components that primarily reflect parasympathetic (PNS) or vagal activity (i.e., indices of vagally mediated HRV) and a combination of both sympathetic (SNS) and PNS influences. Given the physiological relation between the vagus and inflammatory processes, one would expect to find higher HRV, especially indices of vagally-mediated HRV, to be associated with decreased levels of inflammation via the cholinergic anti-inflammatory pathway. However, existing findings here are mixed, such that studies have also shown a positive association between indices of HRV and markers of inflammation. Therefore, the present meta-analysis aimed to synthesize existing studies, estimating the general direction and strength of the relationship between different indices of HRV and inflammatory markers. A systematic search of the literature yielded 2283 studies that were screened for inclusion eligibility (159 studies eligible for inclusion); in sum, 51 studies reported/provided adequate information for inclusion in meta-analyses. Results generally showed negative associations between indices of HRV and markers of inflammation. In this regard, the standard deviation of R-R intervals (SDNN) and power in the high frequency band of HRV (HF-HRV) showed the strongest and most robust associations with inflammatory markers compared to other time- and frequency-domain measures of HRV. Overall, we propose that indices of HRV can be used to index activity of the neurophysiological pathway responsible for adaptively regulating inflammatory processes in humans.

Treatment of neurotrophic keratopathy with minimally invasive corneal neurotisation: long-term clinical outcomes and evidence of corneal reinnervation

AimTo report clinical outcomes and evidence of corneal innervation in patients with neurotrophic keratopathy (NK) treated with minimally invasive corneal neurotisation (MICN) using a sural nerve graft and donor sensory...

Measuring network disruption in neurodegenerative diseases: New approaches using signal analysis

Advanced neuroimaging has increased understanding of the pathogenesis and spread of disease, and offered new therapeutic targets. MRI and positron emission tomography have shown that neurodegenerative diseases including Alzheimer’s disease...

Compound and Dose-Dependent Effects of Two Neonicotinoid Pesticides on Honey Bee (Apis mellifera) Metabolic Physiology.

Use of neonicotinoid pesticides is now ubiquitous, and consequently non-targeted arthropods are exposed to their residues at sub-lethal doses. Exposure to these neurotoxins may be a major contributor to poor honey bee colony health. Few studies have explored how sub lethal exposure to neonicotinoids affects honey bee metabolic physiology, including nutritional and energetic homeostasis, both of which are important for maintaining colony health. Reported here are results from a study of chronic oral exposure of honey bees to two sub lethal concentrations of clothianidin and imidacloprid. Neonicotinoids altered important aspects of honey bee nutritional and metabolic physiology in a compound and dose-dependent manner; both compounds at low doses reduced honey bee body weight. Low-dose clothianidin exposure resulted in bees having protein, lipids, carbohydrates, and glycogen levels similar to newly emerged bees. High-dose clothianidin exposure lowered lipids and glycogen content of bees. High-dose imidacloprid exposure resulted in bees having depressed metabolic rate. Low-dose imidacloprid exposure resulted in bees consuming low and high levels of protein and carbohydrate rich foods, respectively. Results suggest neonicotinoids interfere with honey bee endocrine neurophysiological pathways. Compound and dose-dependent effects might represent respective chemical structural differences determining an observed effect, and thresholds of compound effects on honey bee physiology.