The neuromodulative role of earthing

Neuromodulation is a process of inhibition, stimulation, modification and regulation or therapeutic alteration of activity, electrically and chemically in the peripheral, central or autonomic nervous systems. Direct electric current or electric field alternates the function of nervous system. Coupling the human organism with the Earth directly or via a wire conductor changes the electric potential not only on the surface of the body but also inside it, changing the potential of electric environment of the human organism. Earthing refers to a direct contact with the Earth with bare feet or contact with the Earth with the use of conductive wire attached to the human body during sleeping, or daily activities. During earthing this electric potential equals to electric potential of the Earth and the value of it depends on location, time, atmospheric conditions, moisture of the surface of the Earth. The earthing which changes the density of negative charge in electric environment of the human body influences physiological processes. Our medical hypothesis states that contact with the Earth (earthing) directly or via a conductive wire plays role as a neuromodulative factor, probably primary, which enables the nervous system to be better adapted to the demands of organism and ambient environment. It helps to restore natural, electrical status of the electrical environment of the organism and thus the nervous system. Earthing generates immediate changes in electroencephalography (EEG), surface electromyography (SEMG), and somato-sensory evoked potentials (SSEPs). We hypothesize that earthing through its complex action on bioelectrical environment of human organism and alternations in electrolyte concentrations regulates correct functioning of the nervous system. Earthing significantly influences on the electrical activity of the brain.     

Myoelectric control in neurorehabilitation

A myoelectric signal, or electromyogram (EMG), is the electrical manifestation of a muscle contraction. Through advanced signal processing techniques, information on the neural control of muscles can be extracted from the EMG, and the state of the neuromuscular system can be inferred. Because of its easy accessibility and relatively high signal-to-noise ratio, EMG has been applied as a control signal in several neurorehabilitation devices and applications, such as multi-function prostheses and orthoses, rehabilitation robots, and functional electrical stimulation/therapy. These EMG-based neurorehabilitation modules, which constitute muscle-machine interfaces, are applied for replacement, restoration, or modulation of lost or impaired function in research and clinical settings. The purpose of this review is to discuss the assumptions of EMG-based control and its applications in neurorehabilitation.     

Neural tissue engineering for neuroregeneration and biohybridized interface microsystems in vivo (Part 2)

Neural tissue engineering offers tremendous promise to combat the effects of disease, aging, or injury in the nervous system. Here we review neural tissue engineering with respect to the design of living tissue to directly replace damaged or diseased neural tissue, or to augment the capacity for nervous system regeneration and restore lost function. This article specifically addresses the development and implementation of tissue engineered three-dimensional (3-D) neural constructs and biohybridized neural-electrical microsystems. Living 3-D neural constructs may be "pre-engineered" in vitro with controlled neuroanatomical and functional characteristics for neuroregeneration, to recapitulate lost neuroanatomy, or to serve as a nervous tissue interface to a device. One application being investigated is developing constructs of axonal tracts that, upon transplantation, may facilitate nervous system repair by directly restoring lost connections or by serving as a targeted scaffold to promote host regeneration by exploiting axon-mediated axonal regeneration. In another application, living nervous tissue engineered constructs are being investigated to biohybridize neural-electrical interface microsystems for functional integration with the nervous system. With this design, in vivo neuritic ingrowth and synaptic integration may occur with the living component, potentially exploiting a more natural integration with the nonorganic interface. Overall, the use of tissue engineered 3-D neural constructs may significantly advance regeneration or device-based deficit mitigation in the nervous system that has not been achieved by non-tissue engineering approaches.     

Discrimination of phantom hand sensations elicited by afferent electrical nerve stimulation in below-elbow amputees.

The necessity for a sensory feedback system that would enhance patient acceptability of motorized hand prostheses is now generally acknowledged. Afferent electrical stimulation of the nerves in the amputation stump can convey sensory feedback from prostheses with the advantage of eliciting sensations in the phantom image of the lost hand. Experiments with percutaneous nerve stimulation of the amputation stump in below-elbow amputees showed that with stable electrode conditions, amplitude modulated stimulation was better than frequency modulated stimulation in terms of accuracy, delay, and transinformation both with intermittent and uninterrupted stimulation. With unstable electrode conditions, different results were noticed, since amplitude modulated stimulation is very sensitive even to minor changes in electrode position. It is concluded that afferent electrical nerve stimulation with adequate training and stable electrodes had characteristics of accuracy, transinformation and delay which are good enough to make it a suitable method of conveying information in a prosthesis feedback system.     

Neuroplasticity in amputees: Main implications on bidirectional interfacing of cybernetic hand prostheses

The development of a new generation of hand prostheses that can ideally approximate the human ‘physiological’ performance in terms of movement dexterity and sensory feedback for amputees still poses many open research challenges. The most promising approaches aim at establishing a direct connection with either the central or the peripheral human nervous system by means of invasive or non-invasive neural interfaces. This paper starts from the assumption that a major contribution to derive functional and technical specifications for such interfaces, and even for the whole prosthetic system, can stem from in-depth analysis of the nervous system reorganization following limb amputation. Neuroplasticity can be modulated by the use of hand prostheses both in the acute phase and in the long-term. We hereby critically review the literature concerning neuroplastic phenomena in amputees, in terms of changes at different CNS levels, particularly for their implications on the development of bidirectional neural interfaces for cybernetic hand prostheses. Our analysis of the literature demonstrates that: (1) the level of CNS reorganization could be used as a parameter of the effectiveness achieved by the prosthetic device and its interfaces, in restoring the hand physiological functionality, (2) the prosthetic system could be seen as a neurorehabilitation tool, as it could induce reduction in aberrant plasticity and promote ‘good’ plasticity and (3) new generations of ‘natural’ interfaces can be developed by fully exploiting neuroplastic phenomena to restore neural connections originally governing the lost limb and linking them to the prosthetic system.     

Imaging recovery from stroke

Brain imaging techniques illustrate the plastic potential even of the adult human brain in healthy subjects as in patients with peripheral or central lesions. Recovery of lost function through a persistent structural lesion in the central nervous system is accompanied by a complex and individually variable pattern of reorganisation of the brain. Changes depend on the site of the lesion and are found in both hemispheres, the damaged and the sound one within a pre-existing, widespread and bilateral organised and parallel processing network without the formation of new centres. This implies changes at rest with increased or decreased activity and altered activation patterns during performance of the restituted function. Within the primary motor system an activation at the rim of the infarct, extension into neighbouring representations, which outflow is not disturbed, altered recruitment pattern of motor cortex neurons, and recruitment of ipsilateral direct descending corticospinal tract pathways originating in the sound hemisphere are found. Disruption of the primary system leads to re-weighting of activity between the various representational levels with increased activity in secondary of higher order areas. Early sensory reorganisation indicates the potential for recovery of lost motor function. Behavioural language training in aphasics results in improvement of altered comprehension function, which is related to right hemisphere activation. Thus, reorganisation can be beneficial and training or rehabilitation influence the pattern of reorganisation.     

"Neuro-cardiovascular" surgery: innovations for the treatment and prevention of cardiovascular disease.

The concept of performing surgery on the conduction system and the nervous system of the heart with the use of peripheral nervous tissue, Purkinje fibers or biophysical means, may solve many enigmas concerning the treatment of arrythmias. More importantly, a correlation is suggested between coronary artery disease, the state of depolarization of the myocardial cells, local electrical and magnetic fields, the state of local innervation of coronary blood vessels, the activity of the specialized conducting system, and higher central nervous system centers. This suggested correlation may contribute significantly in the treatment, and eventually, in the prevention of coronary artery disease.     

Neuromodulation, Agency and Autonomy

Neuromodulation consists in altering brain activity to restore mental and physical functions in individuals with neuropsychiatric disorders and brain and spinal cord injuries. This can be achieved by delivering electrical stimulation that excites or inhibits neural tissue, by using electrical signals in the brain to move computer cursors or robotic arms, or by displaying brain activity to subjects who regulate that activity by their own responses to it. As enabling prostheses, deep-brain stimulation and brain–computer interfaces (BCIs) are forms of extended embodiment that become integrated into the individual’s conception of himself as an autonomous agent. In BCIs and neurofeedback, the success or failure of the techniques depends on the interaction between the learner and the trainer. The restoration of agency and autonomy through neuromodulation thus involves neurophysiological, psychological and social factors.     

Doublecortin maintains bipolar shape and nuclear translocation during migration in the adult forebrain

The ability of the mature mammalian nervous system to continually produce neuronal precursors is of considerable importance, as manipulation of this process might one day permit the replacement of cells lost as a result of injury or disease. In mammals, the anterior subventricular zone (SVZa) region is one of the primary sites of adult neurogenesis. Here we show that doublecortin (DCX), a widely used marker for newly generated neurons, when deleted in mice results in a severe morphological defect in the rostral migratory stream and delayed neuronal migration that is independent of direction or responsiveness to Slit chemorepulsion. DCX is required for nuclear translocation and maintenance of bipolar morphology during migration of these cells. Our data identifies a critical function for DCX in the movement of newly generated neurons in the adult brain.     

It takes nerve to tell T and B cells what to do

The existence of an association between the brain and immunity has been documented. Data show that the nervous and immune systems communicate with one another to maintain immune homeostasis. Activated immune cells secrete cytokines that influence central nervous system activity, which in turn, activates output through the peripheral nervous system to regulate the level of immune cell activity and the subsequent magnitude of an immune response. In this review, we will focus our presentation and discussion on the findings that indicate a regulatory role for the peripheral sympathetic nervous system in modulating the level of cytokine and antibody produced during an immune response. Data will be discussed from studies involving the stimulation of the beta2 adrenergic receptor expressed on CD4+ T cells and B cells by norepinephrine or selective agonists. We will also discuss how dysregulation of this line of communication between the nervous and immune systems might contribute to disease development and progression.     

Effects of nicotine on norepinephrine turnover of mice subjected to emotional stress

We tested the hypothesis that nicotine suppresses the emotional and the electrical stress induced by the communication box. We measured the turnover of norepinephrine (NE), a reliable indicator of the sympathetic nervous system activity, in the brown adipose tissue (BAT) and the heart of mice that induced the electrical stress and the emotional stress by the communication box for 2 weeks, of mice treated with the same procedure 10 min after the subcutaneous injections of nicotine, and of mice treated with nicotine injections alone, vs. untreated controls. The results showed that NE turnover in BAT increased most significantly in the animals subjected to electrical stress, followed by those subjected to emotional stress, and then by those administered with nicotine alone, when compared with the control group. Pretreatment with nicotine suppressed the enhancement of NE turnover in both electrical and emotional stress. The sympathetic nervous system activity in the heart was almost the same result as the data of BAT. These results support our hypothesis that nicotine suppresses the enhancement of the emotional and the electrical stresses induced by the communication box in mice.     

Polylysine-Modified PEG-Based Hydrogels to Enhance the Neuro–Electrode Interface

Neural prostheses are a promising technology in the treatment of lost neural function. However, poor biocompatibility of these devices inhibits the formation of a robust neuro–electrode interface. Several factors including mechanical mismatch between the device and tissue, inflammation at the implantation site, and possible electrical damage contribute to this response. Many researchers are investigating polymeric brain mimetic coatings as a means to improve integration with nervous tissue. Specifically, hydrogels, constructs also employed in tissue engineering, have been explored because of their structural and mechanical similarity to native tissue. However, many hydrogel materials (e.g., poly(ethylene glycol) (PEG)) do not support cell adhesion. In this work, we report a technique to enhance the interface between polymeric brain mimetic coatings and neural tissue using adhesion molecules. In particular, polylysine-modified PEG-based hydrogels were synthesized, characterized and shown to promote neural adhesion using a PC12 cell line. In addition, we examined adhesion behavior of a PEG-co-polymer and found that these materials adhere to electrodes for at least 4 weeks. These results suggest that polylysine–PEG hydrogel biomaterials are biocompatible and can enhance stability of chronic neural interfaces.     

Estrogen, cognition and female ageing

Starting from fetal life, estrogens are crucial in determining central gender dimorphism, and an estrogen-induced synaptic plasticity is well evident during puberty and seasonal changes as well as during the ovarian cycle. Estrogens act on the central nervous system (CNS) both through genomic mechanisms, modulating synthesis, release and metabolism of neurotransmitters, neuropeptides and neurosteroids, and through non-genomic mechanisms, influencing electrical excitability, synaptic function and morphological features. Therefore, estrogen's neuroactive effects are multifaceted and encompass a system that ranges from the chemical to the biochemical to the genomic mechanisms, protecting against a wide range of neurotoxic insults. Clinical evidences show that, during the climacteric period, estrogen withdrawal in the limbic system gives rise to modifications in mood, behaviour and cognition and that estrogen administration is able to improve mood and cognitive efficiency in post-menopause. Many biological mechanisms support the hypothesis that estrogens might protect against Alzheimer's disease (AD) by influencing neurotransmission, increasing cerebral blood flow, modulating growth proteins associated with axonal elongation and blunting the neurotoxic effects of beta-amyloid. On the contrary, clinical studies of estrogen replacement therapy (ERT) and cognitive function have reported controversial results, indicating a lack of efficacy of estrogens on cognition in post-menopausal women aged >or=65 years. These findings suggest the presence of a critical period for HRT-related neuroprotection and underlie the potential importance of early initiation of therapy for cognitive benefit. In this review, we shall first describe the multiple effects of steroids in the nervous system, which may be significant in the ageing process. A critical update of HRT use in women and a discussion of possible prospectives for steroid use are subsequently proposed.     

Control of neural prostheses for grasping and reaching

In recent years several neural prostheses have been developed and tested as orthoses or as therapeutic systems for hemiplegic and tetraplegic subjects aiming to improve the upper extremities function. The use of neural prostheses demonstrated that the targeted group of subjects could significantly benefit from functional electrical stimulation that is integrated in goal directed movements. In this paper the control for neural prostheses is explained using available systems that apply either surface or implantable interfaces to sensory-motor systems. Further more, a new strategy that has been tested for control of reaching and grasping within a neural prosthesis especially designed for neurorehabilitation is described. This, so-called, coordination strategy was based on mimicking the output space model of natural control determined in reach/grasp/release movements of healthy humans.     

Untying the Gordian Knot: Contemporary studies of neuronal organization

The nervous systems of invertebrates and vertebrates consist of neuronal networks of varying complexity, and the elucidation of the organization of these networks is essential if we are to understand neural function. Up until the mid- 19th Century gross dissection was the primary tool available to scientists to study the nervous system. The development of neurohistological techniques, electrical stimulation, and observation of neural function in humans and animals following injury added rapidly to our understanding of the nervous system during the following century. Over the last 3 decades investigators seeking to unravel the complexities of neural circuits have made use of analytical methods based upon the biological properties of neurons, including orthograde and retrograde axonal transport of tracer substances, the expression of particular genes and gene products that can be assessed with immunocytochemical or in situ methods, and the imaging of the utilization of oxygen or glucose by active populations of neurons. Advances in neuroscience have led to an enormous expansion in our knowledge of normal neural functioning and how that function is altered by injury or disease. Modern studies of neuronal organization have been at the center of our increased understanding of how the brain works. Anat. Rec. (New Anat.) 253:139–142, 1998. © 1998 Wiley-Liss, Inc.     

Cardiac electrical stunning is a common feature of cardiac arrhythmias

There are many published papers focused on the topic of atrial electrical remodeling, which defined as the shortening and dispersion of effective refractory period (ERP) in patients with paroxysmal or persistent tachyarrhythmias or in animals with long-term rapid atrial pacing. Heart failure could produce the electrical remodeling of sinus node, manifesting the prolongation of corrected sinus node recovery time and sinus cycle length. It might be attributed to decreased hyperpolarization-activated cyclic nucleotide expression of sinus node. Rapid atrial pacing for only 10-15 min, simulating transient atrial tachyarrhythmias, alters sinus node function in human. Termination of atrial flutter by ablation induces reversible changes in sinus node function. After atrial fibrillation (AF) ablation, there was a significant improvement of sinus node function, with an increase in the mean heart rate, maximal heart rate and heart rate range significantly. Reverse electrical remodeling of the ERP occurs at different rates in different regions of the atrium. Previous experiments showed that electrical remodeling of atrial myocardium could be induced by autonomic nervous transmitters and suggested that autonomic nerve activity was an important factor to promote AF episodes. We postulated that electrical remodeling and reverse electrical remodeling are common features of the heart, including atrium, ventricle, sinus node, and conductive system. Inappropriate very rapid or slow electrical depolarization may cause electrical remodeling of the heart, but appropriate rates of electrical depolarization and cessation of rapid stimulation may contribute to the reverse electrical remodeling. So, we forward that a concept defined as cardiac electrical stunning, including electrical remodeling and reverse electrical remodeling, should be a common characteristic and mechanism of cardiac arrhythmias.     

Neuromechanisms of asthma

Autonomic nervous system abnormalities may indeed underlie bronchial hyperreactivity. Imbalances between excitatory (parasympathetic, alpha-adrenergic and noncholinergic excitatory) and inhibitory (beta-adrenergic and non-adrenergic inhibitory) nervous systems at one or more loci could lead to airway hyperreactivity. The current data, however, do not clearly identify any single abnormality in the autonomic nervous system that is ubiquitous in all asthmatic patients. Rather, it appears that bronchial hyperreactivity results from many factors and that distinct autonomic nervous system abnormalities may occur in individual subjects. Future studies of how autonomic control of airway function in asthma may be disordered should prove useful in gaining a better understanding of the pathophysiology of asthma and in designing new treatment modalities.     

Optical studies of early developing cardiac and neural activities using voltage-sensitive dyes

Using optical methods for monitoring cellular electrical activity based on voltage-sensitive dyes, we have overcome several obstacles to the study of electrical function in the embryonic heart and central nervous system during early development. We have been able to monitor, for the first time, spontaneous electrical activity in the pre-fused cardiac primordia in early chick embryos at the 6- and early 7-somite stages of development and to follow the early development of electrical activity in the pre-contractile heart at the 7- to 9-somite stages. In addition, we have monitored neural responses in the early embryonic chick brain stem by optical means, and determined the spatial pattern of the response.     

Pattern generation in the buccal system of freely behaving Lymnaea stagnalis

Central pattern generators (CPGs) are neuronal circuits that drive active repeated movements such as walking or swimming. Although CPGs are, by definition, active in isolated central nervous systems, sensory input is thought play an important role in adjusting the output of the CPGs to meet specific behavioral requirements of intact animals. We investigated, in freely behaving snails (Lymnaea stagnalis), how the buccal CPG is used during two different behaviors, feeding and egg laying. Analysis of the relationship between unit activity recorded from buccal nerves and the movements of the buccal mass showed that electrical activity in laterobuccal/ventrobuccal (LB/VB) nerves was as predicted from in vitro data, but electrical activity in the posterior jugalis nerve was not. Autodensity and interval histograms showed that during feeding the CPG produces a much stronger rhythm than during egg laying. The phase relationship between electrical activity and buccal movement changed little between the two behaviors. Fitting the spike trains recorded during the two behaviors with a simple model revealed differences in the patterns of electrical activity produced by the buccal system during the two behaviors investigated. During egg laying the bursts contained less spikes, and the number of spikes per burst was significantly more variable than during feeding. The time between two bursts of in a spike train was longer during egg laying than during feeding. The data show what the qualitative and quantitative differences are between two motor patterns produced by the buccal system of freely behaving Lymnaea stagnalis.