Nervous System Responses Research Articles

Potential drug interactions with garlic

Every drug may cause central nervous system, gastrointestinal tract or cardiovascular system adverse drugs reactions (ADRs). At the same time, doctors often do not have sufficient information about possible food-drug interactions, in particular, garlic. But this spice is shown to increase the risks of developing ADRs. From the beginning of the 20th century to the present, garlic has been the subject of many chemical studies, which have revealed some differences in the chemical composition of the studied preparation (fresh or stored garlic). The most important chemical ingredients found in garlic are divided into two groups: sulfur-containing (allicin [diallyl thiosulfinate], allyl methanesulfinate, alliin [S-allyl-L-cysteine sulfoxide, diallyl disulfide, DADS], S-allylmethyl cysteine, diallyl trisulfide [diallyl trisulfide, DATS], allyl methyl trisulfide, allyl methyl disulfide, diallyl tetrasulfide, allyl methyl tetrasulfide, dimethyl trisulfide, diallyl sulfide, 2-vinyl-4-H1,3-dithiine, 3-vinyl-4.-H1,2-dithiin) and sulfur-free compounds. Most of the pharmacological effects of garlic are due to sulfur compounds, in particular allicin. In animal, in vitro and clinical studies, it has been shown that garlic can interact with various drug througt pharmacokinetic or pharmacodynamic way. For example, garlic extract has shown to inhibit the metabolic activity of CYP2C9*1, 2C19, 3A4, 3A5, 3A7, but not CYP2D6. It has also been shown that garlic can affect the function thrombocyte and blood clotting, which leads to an increased risk of bleeding, which is especially important in the case of its simultaneous use with antiplatelet agents and/or anticoagulants. This article provides an overview of the open literature on the risks and benefits of the simultaneous use of drugs and products containing garlic.

Psychophysiological underpinnings of proactive and reactive aggression in young men and women

Reactive aggression is posited to occur as a result of hypersensitivity to threat, whereas fearlessness may drive proactive aggression. This study aimed to test if physiological fear reactivity differentially relates to self-report reactive and proactive aggression using immersive virtual reality fear (VR) induction. We collected subjective fear ratings and sympathetic (SNS; skin conductance) and parasympathetic (PNS; respiratory sinus arrhythmia) nervous system reactivity during an interactive VR horror video. Results showed that for men and women, reactive aggression was related to heightened SNS fear reactivity. For men, proactive aggression was related to hypoarousal of the PNS and SNS (coinhibition) during fear induction, whereas augmented PNS was related to proactive aggression in women. These results support the fearlessness hypothesis for proactive aggression in men, but this does not replicate in women. By contrast, hypersensitivity to fear is related to reactive aggression for both men and women.

Psychophysiological dynamics of emotional reactivity: Interindividual reactivity characterization and prediction by a machine learning approach

The fast reaction of the autonomic nervous system (ANS) to an emotional challenge (EC) is the result of a functional coupling between parasympathetic (PNS) and sympathetic (SNS) branches. This coupling can be characterized by measures of cross-correlations between electrodermal activity (EDA) (under the influence of the SNS) and the RR interval (the interval between R peaks) (under the influence of the PNS and the SNS). Significant interindividual variability has previously been reported in SNS-PNS coupling in emotional situations, and the present study aimed to identify interindividual cross-correlation variability in ANS reactivity. We therefore studied EDA and the RR interval in 62 healthy subjects, recorded during a 24-minute EC. A Gaussian Mixture Model was used to cluster tonic EDA-RR cross-correlations during the EC. This identified two clusters that were characterized by significant or non-significant cross-correlations (SCC and NCC clusters, respectively). The SCC cluster reported higher negative emotion after the EC, while the NCC cluster reported higher scores on the Center for Epidemiologic Studies–Depression scale. The latter finding suggests that NCC is a pathological mood pattern with altered negative perception. Furthermore, a machine learning model that included three parameters indexing the functionality of both branches of the ANS, measured at baseline, predicted cluster membership. Our results are a first step in detecting dysfunctional ANS reactivity in general population.

Low-Intensity Laser Therapy As a Method to Reduce Stress Responses after Septoplasty.

The aim of the study was to evaluate the effectiveness of the use of photobiomodulation therapy (PBMT) to minimize acute pain in the early postoperative period in patients after septoplasty. In total, 62patients underwent septoplasty under general anesthesia (40 men and 22 women, 18-44 years old) followed by nasal tamponade. Patients of the 1st group did not undergo PBMT, and patients of the 2nd group received PBMT 3, 6, and 24 h after septoplasty (infrared pulsed laser radiation, λ = 0.890 μm, P = 10 W, 2min in the projection of the wings of the nose). After 48 h, after the removal of tampons, intranasal PBMT with a nozzle in the red range, with λ = 0.63 μm, P = 8 mW, 2 min. ULF, HF, LF, and total power of heart rate variability (HRV), pain syndrome was assessed. ULF, LF, HF, total HRV power were significantly lower in group 2, compared to group 1. In the period from 6 to 24 h after septoplasty, patients of group 1 experienced higher pain than patients with PBMT (p < 0.001). The use of PBMT after septoplasty against the background of nasal tamponade helps to reduce the severity of pain syndrome and the inflammatory response to surgical stress and, consequently, leads to less pronounced changes in the autonomic nervous system in response to surgical stress.

Immunohistochemical Study of ASC Expression and Distribution in the Hippocampus of an Aged Murine Model of Alzheimer's Disease.

Neuroinflammation is involved in the pathogenesis of neurodegenerative diseases such as Alzheimer’s disease (AD), and is notably dependent on age. One important inflammatory pathway exerted by innate immune cells of the nervous system in response to danger signals is mediated by inflammasomes (IF) and leads to the generation of potent pro-inflammatory cytokines. The protein “apoptosis-associated speck-like protein containing a caspase recruitment domain” (ASC) modulates IF activation but has also other functions which are crucial in AD. We intended to characterize immunohistochemically ASC and pattern recognition receptors (PRR) of IF in the hippocampus (HP) of the transgenic mouse model Tg2576 (APP), in which amyloid-beta (Aβ) pathology is directly dependent on age. We show in old-aged APP a significant amount of ASC in microglia and astrocytes associated withAβ plaques, in the absence of PRR described by others in glial cells. In addition, APP developed foci with clusters of extracellular ASC granules not spatiallyrelated to Aβ plaques, which density correlated with the advanced age of mice and AD development. Clusters were associated withspecific astrocytes characterized by their enlarged ring-shaped process terminals, ASC content, and frequent perivascular location. Their possible implication in ASC clearance and propagation of inflammation is discussed.

Interface, interaction, and intelligence in generalized brain–computer interfaces

A brain-computer interface (BCI) establishes a direct communication channel between a brain and an external device. With recent advances in neurotechnology and artificial intelligence (AI), the brain signals in BCI communication have been advanced from sensation and perception to higher-level cognition activities. While the field of BCI has grown rapidly in the past decades, the core technologies and innovative ideas behind seemingly unrelated BCI systems have never been summarized from an evolutionary point of view. Here, we review various BCI paradigms and present an evolutionary model of generalized BCI technology which comprises three stages: interface, interaction, and intelligence (I3). We also highlight challenges, opportunities, and future perspectives in the development of new BCI technology.

Effects of Combined HIIT and Stroop on Strength Manifestations, Serve Speed and Accuracy in Recreational Tennis Players

Background: The importance of the serve in tennis players’ performance is well known but no previous studies have analyzed the effects of both physical and cognitive fatigue on the speed and accuracy of the serve. This study analyzed the effect of a High-Intensity Interval Training (HIIT) with and without cognitive load on serve speed and accuracy, spirometry, and strength manifestation. Methods: 32 recreational players (25 men and 7 women; aged 21.40 ± 1.52 years) performed a HIIT and a HIIT with a Stroop in recovery phases before performing a series of tennis services. Speed and accuracy of the services, spirometry, and strength manifestations were registered. Results: The main findings of the study showed that strength manifestations and spirometry were not affected by either protocol. A decrease in serve speed was observed in both protocols (p &lt; 0.001) but service accuracy did not show impairments (p = 0.66). Conclusion: A combination of physical and mental fatigue may decrease serve speed but will not affect strength manifestations or spirometry negatively. These results could be caused by a response of the central nervous system to maintain the accuracy of the ball in presence of fatigue.

Uncovering the pathophysiology of irritable bowel syndrome by exploring the gut-brain axis: a narrative review.

ObjectiveTo improve the pathophysiological understanding of irritable bowel syndrome (IBS) by exploring the gut-brain axis.BackgroundDisorders of gut-brain interaction (DGBIs) are gastrointestinal (GI) disorders in which alterations in bowel functions occur. IBS, which is one of the most studied DGBIs, is linked with abdominal distress or pain without obvious structural or biochemical anomalies.MethodsThe etiology of IBS has not been clearly described but is known to be multifactorial, involving GI motility changes, post-infectious reactivity, visceral hypersensitivity, gut-brain interactions, microbiota dysbiosis, small intestinal bacterial overgrowth, food sensitivity, carbohydrate malabsorption, and intestinal inflammation.ConclusionsOne of the main features of IBS is the occurrence of structural and functional disruptions in the gut-brain axis, which alter reflective and perceptual nervous system reactions. Herein, we provide a brief summary of this topic. Furthermore, we discuss animal models, which are important in the study of IBS, especially as it is linked with stressors. These animal models cannot fully represent the human disease but serve as important tools for understanding this complicated disorder. In the future, technologies, such as organ-on-a-chip models and metabolomics, will provide novel information regarding the pathophysiology of IBS, which will play an important role in treatment development. Finally, we take a brief glance at how acupuncture treatments may hold potential for patients with IBS.

Multiple Sclerosis: A Neurological Disorder

Multiple sclerosis (MS)is a long lasting, chronic and auto-immune disease which affects central nervous system. In this auto-immune disease, our own immune system damages the body.It is a disabling disease of spinal cord and brain, specially deteriorates optic nerve of eyes. The disease is caused when immune system of the body attacks on myelin sheath which is a protective layer of neurons; the structural and functional unit of nervous system. This sheath protects the nerve fibers. Damage to myelin sheath exposes the nerve fibers, which slows down or blocks the nerve impulse passing through the nerve. This disease appears between the ageof 20 to 50 years in most cases. Statistics reveal that it is more common in women than men. The causes of this disease are unknown but scientists believe that the risk factor of this disease is the combination of genetics and environment. Its symptoms include effects on body movements involving loss of balance, weakness or numbness in limbs, dizziness, body pains, electric shock sensations specially in neck region,fatigue,difficulty swallowing, slurred speechand vertigo.It also involves problems relating sexual, bowel and bladder functions. It may also cause depression and anxiety.The symptoms are different in children than adults. It starts with acute encephalomyelitis, including fever, stiff neck, seizures, coma and confusion. It these symptoms persist, doctor should be consulted immediately.&#x0D; Research has shown that there are some factors whichcan increase the chances of its development. These factors include;age,climate, Vitamin D and other auto-immune diseases. MS can occur at any age in one’s life but its onset is common between 20 to 50 years. The risk of developing of MS in twin babies is 1 in 4 cases. However, younger and older people can be affected too.Considering the factor of climate, MS is found to be more common in countries found in temperate regions of the world. Statistics have shown that MS was common in people living in New Zealand, Canada, USA and many other European countries. All of us know what is the importance of vitamins. It has been observed that lower levels of Vitamin D and decreased sunlight exposure are related with greater risk of this disease. Many people suffer from auto-immune diseases for example pernicious anemia, Inflammatory bowel disease, Type I Diabetes Mellitus and thyroid problems. Recent studies show that person already facing the trouble of auto-immune disease is at higher risk of getting MS. Multiple sclerosis (MS) has been divided into four basic types: Primary progressive MS (PPMS), Secondary Progressive MS (SPMS), Progressive Relapsing MS (PRMS) and Relapsing Remitting MS (RRMS).&#x0D; Recent findings from a National MS Society estimated that nearly 1 million people in the United States are affected with MS. This is more than double the last reported number, and the first national research on MS prevalence since 1975. The society also estimated that 2.3 million people live with MS globally.&#x0D; There is no specific laboratory or diagnostic test to check for MS. For detection of MS, differential diagnosis is used in which signs, symptoms and patients condition is used to rule out the overall scenario. Some blood tests are recommended by doctors which check specific biomarkers associated with MS. MRIis helpfuland it can reveal some areas of spinal cord and brain to see lesions.Spinal tap in which a small sample of cerebrospinal fluid is removed from the spinal canal for laboratory analysis. This sample can show abnormalities in antibodies that are associated with MS.Electric signals produced by nervous system in response to specific stimuli are recorded in a test called Evoked potential test. It’s unfortunate that there is no complete cure of this disease up-till now. Treatment helps tospeed up the, slowing the progression of the disease and managing MS symptoms to help patient live a better life. Treatment for attacks includes the useof corticosteroids and plasma exchange.&#x0D; Previously, it was thought that this disease is uncommon in Pakistan. But new data shows its prevalence to be 10 in 10,0000 of population. It is affecting the Pakistani population on same patterns as found in West. It is found to be more common in women than men. It has been affecting more people who are passing third decade of life. Among its types, Relapsing-Remitting MS (RRMS) is more common in Pakistan. It’s unfortunate that the reports about this disease are few in numbers and there is a need to conduct a thorough research in hope of finding a complete cure of this disease and making the life of patients affected by it much more comfortable.

Heart Rate Variability of Children with Mitral Valve Prolapse in Orthostatic Test

The purpose of the research was to study the state of autonomic regulation in prepubertal children with mitral valve prolapse during an orthostatic test Materials and methods. The study involved 2 groups: the main – 26 children aged 10-11 years with mitral valve prolapse, and a control group – 22 relatively healthy children. The adaptive mechanisms were monitored by analyzing heart rate variability. All children participated in a cardiorhythmic examination at rest lying down and during an active orthostatic test. Results and discussion. Among the indicators that had significant differences, the indicators of regulatory process adequacy index and mode amplitude should be noted. In the group of children with mitral valve prolapse, an increase of the regulatory process adequacy index indicated the predominance of the functioning of the sinus node over the activity of the sympathetic division of the autonomic nervous system. An increase in the adequacy index and mode amplitude indicates the connection of the central structures of rhythm control (subcortical rhythms) during a change in body position. Stress index also increased. This index of tension of regulatory systems shows the activity of the mechanisms of sympathetic regulation, the state of central regulation. Children in the control group had a well-coordinated response of the sympathetic nervous system to the orthostatic test: the low frequency spectrum and very low frequency indicators increased. While in main group, the value of low frequency spectrum (the work of the sinus node) increased, the value of very low frequency (the reaction of the central structures of the nervous system) decreased. This indicates dysfunction of the most important reactions, which also affects the daily activities of children, increases the risk of mitral valve prolapse complications. Conclusion. In children with mitral valve prolapse, the absence of a pronounced typical reaction to an ortho test is a reflection of an adaptive-regulatory overstrain in conditions of morphological determinacy of connective tissue dysplasia, which are trying to ensure the adequacy of intracardiac hemodynamics. The data obtained will be useful for predicting the reaction of the body of children with mitral valve prolapse to physical activity of varying intensity

Explanation Within Arm’s Reach: A Predictive Processing Framework for Single Arm Use in Octopuses

Octopuses are highly intelligent animals with vertebrate-like cognitive and behavioural repertoires. Despite these similarities, vertebrate-based models of cognition and behaviour cannot always be successfully applied to octopuses, due to the structural and functional characteristics that have evolved in their nervous system in response to the unique challenges posed by octopus morphology. For instance, the octopus brain does not support a somatotopic or point-for-point spatial map of the body—an important feature of vertebrate nervous systems. Thus, while octopuses are capable of motor tasks whose vertebrate counterparts require detailed interoceptive monitoring, these movements may not be explainable using motor control frameworks premised on internal spatial representation. One such motor task is the extension of a single arm. The ability of octopuses to select and use a single arm without the guidance of a somatotopic map has been regarded as a motor control puzzle. In an attempt at a solution, this paper develops a predictive processing account of single-arm extension in octopuses.

The Lausanne Infant Crying Stress Paradigm: Validation of an Early Postpartum Stress Paradigm with Women at Low vs. High Risk of Childbirth-Related Posttraumatic Stress Disorder

Stress reactivity is typically investigated in laboratory settings, which is inadequate for mothers in maternity settings. This study aimed at validating the Lausanne Infant Crying Stress Paradigm (LICSP) as a new psychosocial stress paradigm eliciting psychophysiological stress reactivity in early postpartum mothers (n = 52) and to compare stress reactivity in women at low (n = 28) vs. high risk (n = 24) of childbirth-related posttraumatic stress disorder (CB-PTSD). Stress reactivity was assessed at pre-, peri-, and post-stress levels through salivary cortisol, heart rate variability (high-frequency (HF) power, low-frequency (LF) power, and LF/HF ratio), and perceived stress via a visual analog scale. Significant time effects were observed for all stress reactivity outcomes in the total sample (all p < 0.01). When adjusting for perceived life threat for the infant during childbirth, high-risk mothers reported higher perceived stress (p < 0.001, d = 0.91) and had lower salivary cortisol release (p = 0.023, d = 0.53), lower LF/HF ratio (p < 0.001, d = 0.93), and marginally higher HF power (p = 0.07, d = 0.53) than low-risk women. In conclusion, the LICSP induces subjective stress and autonomic nervous system (ANS) reactivity in maternity settings. High-risk mothers showed higher perceived stress and altered ANS and hypothalamic–pituitary–adrenal reactivity when adjusting for infant life threat. Ultimately, the LICSP could stimulate (CB-)PTSD research.

Sequential expression of neutrophil chemoattractants in cerebrospinal fluid after subarachnoid hemorrhage

ObjectiveNeutrophils induce inflammation through the exocytosis of cytotoxic granule proteins. Recently, neutrophils have been reported to be an independent parameter associated with unfavorable outcomes after subarachnoid hemorrhage (SAH). However, the mechanism by which neutrophils accumulate within the CSF after SAH remains undetermined. MethodsConcentrations of C5a, epithelial neutrophil activating peptide 78 (ENA-78), interleukin-8 (IL-8), growth-regulated oncogene-α (GRO-α), neutrophil gelatinase-associated lipocalin (NGAL) and myeloperoxidase (MPO) were measured serially until day 14 in the CSF of 10 patients with SAH. CSF samples obtained from patients suffering from unruptured aneurysms were used as controls. ResultsThe concentrations of C5a and ENA-78 were significantly increased on day 1, while those of IL-8 and GRO-α significantly increased during days 3–7 compared with those of the control samples. The levels of NGAL and MPO, components of neutrophil granules, significantly increased during days 1–5 and days 1–3, respectively, after SAH and gradually decreased thereafter. The correlations between ENA-78 and C5a on day 1, IL-8 and GRO-α on days 3–7, and NGAL and MPO on days 1–3 were significant. ConclusionThese neutrophil chemoattractants might be serially involved in the infiltration of neutrophils into the CSF after SAH. Migrated neutrophils play an important role in inflammatory reactions in the central nervous system after SAH.

CYP2D6 in the Brain: Potential Impact on Adverse Drug Reactions in the Central Nervous System-Results From the ADRED Study.

Cytochrome P450 (CYP) 2D6 is a polymorphic enzyme expressed in the central nervous system (CNS), important in drug metabolism and with a potentially constitutive role in CNS function such as vigilance. This study aimed to analyze variability in CYP2D6 activity linked to vigilance-related adverse drug reactions (ADRs) in the CNS. A dataset of N = 2939 ADR cases of the prospective multicenter observational trial in emergency departments (EDs) (ADRED; trial registration: DRKS-ID: DRKS00008979) was analyzed. Dizziness as the most frequent reported CNS ADR symptom (12.7% of patients, n = 372) related to vigilance was chosen as the outcome. The association of dizziness with CYP2D6 activity markers was analyzed. The number of CYP2D6 substrates taken, a CYP2D6 saturation score (no, moderate, and strong saturation), a CYP2D6 saturation/inhibition score (no, weak, moderate, and strong), and composed CYP2D6 activity using a genotyped subsample (n = 740) calculating additive effects of genotype and CYP2D6 saturation by drug exposure were used as CYP2D6 activity markers. Effects were compared to other frequent nonvigilance-related CNS ADR symptoms (syncope and headache). Secondary analyses were conducted to control for other ADR symptoms frequently associated with dizziness (syncope, nausea, and falls). The majority of all patients (64.5%, n = 1895) took at least one drug metabolized by CYP2D6. Around a third took a CNS drug (32.5%, n = 955). The chance to present with drug-related dizziness to the ED increased with each CYP2D6 substrate taken by OR 1.11 [1.01–1.23]. Presenting with drug-related dizziness was more likely with CYP2D6 saturation and saturation/inhibition (both OR 1.27 [1.00–1.60]). The composed CYP2D6 activity was positively associated with dizziness (p = 0.028), while poorer activity affected patients more often with dizziness as an ADR. In contrast, nonvigilance-related ADR symptoms such as syncope and nausea were not consistently significantly associated with CYP2D6 activity markers. This study shows an association between the number of CYP2D6 substrates, the predicted CYP2D6 activity, and the occurrence of dizziness as a CNS ADR symptom. As dizziness is a vigilance-related CNS symptom, patients with low CYP2D6 activity might be more vulnerable to drug-related dizziness. This study underlines the need for understanding individual drug metabolism activity and individual risks for ADRs.

Autonomic Nervous System Response to Psychosocial Stress in Anorexia Nervosa: A Cross-Sectional and Controlled Study.

To foster understanding in the psychopathology of patients with anorexia nervosa (PAN) at the psychological and physiological level, standardized experimental studies on reliable biomarkers are needed, especially due to the lack of disorder-specific samples. To this end, the autonomic nervous system (ANS) response to a psychosocial stressor was investigated in n = 19 PAN (BMI: 18.7 ± 3.3 kg/m2), age, and gender-matched to n = 19 healthy controls (HC; BMI: 24.23 ± 3.0 kg/m2). For this purpose, heart rate (HR) and heart rate variability (HRV) parameters were assessed in a cross-sectional study design under two experimental conditions: (1) rest and (2) stress (Trier Social Stress Test). In addition, psychological indicators of stress were assessed. An 2 × 2 × 8 ANOVA demonstrated similar HR and HRV patterns (except LF-HRV) between PAN and HC at rest. Under stress, PAN (vs. HC) demonstrated a blunted HR [condition*time*group: F(2.91, 104.98) = 9.326, p = 0.000, η2 = 0.206] and an attenuated HRV response (reduced SNS/PNS reactivity). Significant effects of stress appraisal (SA) and BMI on HRV-reactivity were revealed. SA on SDNN = Condition*time*SA = F(4.12, 140.15) = 2.676, p = 0.033, η2 = 0.073. BMI on LF/HF-Ratio = Condition*time*BMI = F(3.53, 60.16) = 3.339, p = 0.019, η2 = 0.164. Psychological indices suggested higher levels of chronic and appraised stress in PAN relative to HC. Additional analyses demonstrated that ED-symptoms are highly correlated with the latter constructs, as well as with psychological burden, but not with weight. Further, it was shown that abnormalities in reactivity persisted despite normalized ANS activity. Overall, we suggested that besides weight recovery, improvement in stress appraisal could be beneficial for cardiac health. In this light, a combination of therapy (e.g., development and activation of coping skills, cognitive reappraisal) and biofeedback training may improve treatment outcomes and regulate stress reactivity.

Traumatic brain injury: Estimate of the age of the injury based on neuroinflammation, endothelial activation markers and adhesion molecules.

Studies on traumatic brain injury (TBI) are applicable not only in the clinical context, but also in the forensic field. Over time, the literature has accumulated scientific evidence supporting the use of specific histopathological tests in dating traumatic brain injuries. In primary damage, cell death occurs by necrosis/apoptosis. In secondary injury, the underlying mechanisms are inflammation and ischemia. The inflammatory response of the central nervous system (CNS) follows the common steps of the innate response. In head injury, the blood brain barrier (BBB) undergoes both functional damage and, subsequently, finer structural changes. Scientific evidence has shown modifications of the junctional-endothelial system that favors the extravasation of immunocompetent cells. The histological evaluation of the subdural hematoma, of the cerebral contusions, of the diffuse axonal damage can certainly bring useful elements, with limitations, to the chronological evaluation of the lesions. Many markers have been used to better define the dating of the head injury. Several authors also analyzed the usefulness of secondary damage markers in brain tissue. The progress achieved with immunohistochemistry is significant compared to the use of routine staining. With immunohistochemistry it is possible to identify much narrower and more precise time intervals and, above all, with greater probative reliability. Recently attention has been paid to the modification of structural proteins and miRNAs. Future research is already started and entrusted to multidisciplinary teams that know how to combine their specific skills in search of a reproducible standard of known and sufficient accuracy.

Nonlinear Modeling of Cortical Responses to Mechanical Wrist Perturbations Using the NARMAX Method.

Nonlinear modeling of cortical responses (EEG) to wrist perturbations allows for the quantification of cortical sensorimotor function in healthy and neurologically impaired individuals. A common model structure reflecting key characteristics shared across healthy individuals may provide a reference for future clinical studies investigating abnormal cortical responses associated with sensorimotor impairments. Thus, the goal of our study is to identify this common model structure and therefore to build a nonlinear dynamic model of cortical responses, using nonlinear autoregressive-moving-average model with exogenous inputs (NARMAX). EEG was recorded from ten participants when receiving continuous wrist perturbations. A common model structure detection method was developed for identifying a common NARMAX model structure across all participants, with individualized parameter values. The results were compared to conventional subject-specific models. The proposed method achieved 93.91% variance accounted for (VAF) when implementing a one-step-ahead prediction and around 50% VAF for a k-step ahead prediction (k = 3), without a substantial drop of VAF as compare to subject-specific models. The estimated common structure suggests that the measured cortical response is a mixed outcome of the nonlinear transformation of external inputs and local neuronal interactions or inherent neuronal dynamics at the cortex. The proposed method well determined the common characteristics across subjects in the cortical responses to wrist perturbations. It provides new insights into the human sensorimotor nervous system in response to somatosensory inputs and paves the way for future translational studies on assessments of sensorimotor impairments using our modeling approach.

Premature complexes, anxiety and quality of life

Premature complexes can be indicative of an increased cardiac risk or can contribute to the initiation or deterioration of heart failure in particular in the presence of organic heart disease. Most premature complexes are benign. The postextrasystolic pause or the augmented postextrasystolic premature beat may cause the following symptoms: feeling of askipped beat or the sensation of apounding heart beat causing the feeling "that something is seriously wrong". It is mentioned that premature beats cause an unconscious reaction of the autonomic nervous system. Symptoms related to premature complexes may cause uneasiness or franc anxiety which may itself intensify the symptoms. This may cause apanic reaction which may be associated with shortness of breath or angina of the chest mimicking dyspnea of heart failure of an acute coronary syndrome. Along the "vicious cycle of anxiety" it is demonstrated how patients may be comforted. In addition, the panic disorder itself should be treated by cognitive behavioral or psychodynamic therapy.

The Role of Mediobasal Hypothalamic PACAP in the Control of Body Weight and Metabolism.

Body energy homeostasis results from balancing energy intake and energy expenditure. Central nervous system administration of pituitary adenylate cyclase activating polypeptide (PACAP) dramatically alters metabolic function, but the physiologic mechanism of this neuropeptide remains poorly defined. PACAP is expressed in the mediobasal hypothalamus (MBH), a brain area essential for energy balance. Ventromedial hypothalamic nucleus (VMN) neurons contain, by far, the largest and most dense population of PACAP in the medial hypothalamus. This region is involved in coordinating the sympathetic nervous system in response to metabolic cues in order to re-establish energy homeostasis. Additionally, the metabolic cue of leptin signaling in the VMN regulates PACAP expression. We hypothesized that PACAP may play a role in the various effector systems of energy homeostasis, and tested its role by using VMN-directed, but MBH encompassing, adeno-associated virus (AAVCre) injections to ablate Adcyap1 (gene coding for PACAP) in mice (Adcyap1MBHKO mice). Adcyap1MBHKO mice rapidly gained body weight and adiposity, becoming hyperinsulinemic and hyperglycemic. Adcyap1MBHKO mice exhibited decreased oxygen consumption (VO2), without changes in activity. These effects appear to be due at least in part to brown adipose tissue (BAT) dysfunction, and we show that PACAP-expressing cells in the MBH can stimulate BAT thermogenesis. While we observed disruption of glucose clearance during hyperinsulinemic/euglycemic clamp studies in obese Adcyap1MBHKO mice, these parameters were normal prior to the onset of obesity. Thus, MBH PACAP plays important roles in the regulation of metabolic rate and energy balance through multiple effector systems on multiple time scales, which highlight the diverse set of functions for PACAP in overall energy homeostasis.

Neuroinflammation and Tinnitus.

Neuroinflammation is the central nervous system's response to: injury, infection, and abnormal neural activity. Inflammatory processes are known to mediate many diseases, and recently evidence indicates that neuroinflammation underlies hearing disorders such as presbyacusis, middle-ear disease, ototoxicity, noise-induced hearing loss, and tinnitus. This chapter provides a review of the role of neuroinflammation in the etiology and treatment of tinnitus. Specifically, our research team has demonstrated that both tumor necrosis factor alpha (TNF-α) and calpain signaling pathways are involved in noise-induced tinnitus and that blocking them yielded therapeutic effects on tinnitus. Other efforts such as controlling acute inflammatory response via specialized pro-resolving mediators may help provide insight into preventing and treating tinnitus-related inflammatory processes.