Impulse Patterns Research Articles

Oscillations, resonances and noise: basis of flexible neuronal pattern generation

Modulation of neuronal impulse pattern is examined by means of a simplified Hodgkin–Huxley type computer model which refers to experimental recordings of cold receptor discharges. This model essentially consists of two potentially oscillating subsystems: a spike generator and a subthreshold oscillator. With addition of noise the model successfully mimics the major types of experimentally recorded impulse patterns and thereby elucidate different resonance behaviors. (1) There is a range of rhythmic spiking or bursting where the spike generator is strongly coupled to the subthreshold oscillator. (2) There is a pacemaker activity of more complex interactions where the spike generator has overtaken part of the control. (3) There is a situation where the two subsystems are decoupled and only resonate with the help of noise.

Unregulated Internet Usage: Addiction, Habit, or Deficient Self-Regulation?

Recent reports of problematic forms of Internet usage bring new currency to the problem of "media addictions" that have long been the subject of both popular and scholarly writings. The research in this article reconsidered such behavior as deficient self-regulation within the framework of A. Bandura's (1991) theory of self-regulation. In this framework, behavior patterns that have been called media addictions lie at one extreme of a continuum of unregulated media behavior that extends from normally impulsive media consumption patterns to extremely problematic behavior that might properly be termed pathological. These unregulated media behaviors are the product of deficient self-regulatory processes through which media consumers monitor, judge, and adjust their own behavior, processes that may be found in all media consumers. The impact of deficient self-regulation on media behavior was examined in a sample of 465 college students. A measure of deficient self-regulation drawn from the diagnostic criteria used in past studies of pathological Internet usage was significantly and positively correlated to Internet use across the entire range of consumption, including among normal users who showed relatively few of the "symptoms." A path analysis demonstrated that depression and media habits formed to alleviate depressed moods undermined self-regulation and led to increased Internet usage.

Extra Spike Formation in Sensory Neurons and the Disruption of Afferent Spike Patterning

The peculiar pseudounipolar geometry of primary sensory neurons can lead to ectopic generation of “extra spikes” in the region of the dorsal root ganglion potentially disrupting the fidelity of afferent signaling. We have used an explicit model of myelinated vertebrate sensory neurons to investigate the location and mechanism of extra spike formation, and its consequences for distortion of afferent impulse patterning. Extra spikes originate in the initial segment axon under conditions in which the soma spike becomes delayed and broadened. The broadened soma spike then re-excites membrane it has just passed over, initiating an extra spike which propagates outwards into the main conducting axon. Extra spike formation depends on cell geometry, electrical excitability, and the recent history of impulse activity. Extra spikes add to the impulse barrage traveling toward the spinal cord, but they also travel antidromically in the peripheral nerve colliding with and occluding normal orthodromic spikes. As a result there is no net increase in afferent spike number. However, extra spikes render firing more staccato by increasing the number of short and long interspike intervals in the train at the expense of intermediate intervals. There may also be more complex changes in the pattern of afferent spike trains, and hence in afferent signaling.

Estimating the afferent and efferent temporal interval entropy of neuronal discharge for single spike trains

We define a biological communication system at the level of a single neuron and quantify the temporal variability of afferent and efferent impulse patterns by means of an interval entropy measure. Two signal transmission conditions which bound a physiologically plausible range of transmission possibilities are explored. The number of efferent synapses is predicted by matching estimates of the mean efferent entropy to the total afferent entropy.

Sympathetic nerve activity to amputated lower leg in humans: Evidence of altered skin vasoconstrictor discharge

Transection of a peripheral nerve in the cat is known to cause a regional change in sympathetic impulse pattern. Our aim was to determine whether microneurography can be used to study sympathetic activity in the transected nerve of human amputees, and whether any such activity shows an abnormal pattern similar to that observed in the cat. Seven successful sympathetic recording sessions were performed in the peroneal nerve of four subjects with posttraumatic transtibial leg amputation; one of them was studied on four occasions. Muscle nerve sympathetic activity (MSA) was detected in all four subjects. Skin nerve sympathetic activity (SSA) was found in one patient only, but on three occasions. It was more difficult to obtain high quality sympathetic recordings than for intact nerves, particularly in patients amputated many years before our studies. MSA showed a qualitatively normal pattern at rest and during various manoeuvres. In three recordings from skin nerve fascicles without innervation zone, SSA displayed normal characteristics at room temperature and qualitatively normal responses to arousal stimuli and various manoeuvres. During body cooling there was an abnormal shift in SSA pattern with a reduction in burst duration instead of the increase occurring normally. Cardiac rhythmicity of SSA was more pronounced during body cooling than during body heating. This is also a reversal of the normal pattern. The abnormal SSA pattern during body cooling suggests increased baroreflex regulation of cutaneous vasoconstrictor neurones, similar to the change after nerve transection in the cat. This is the first time that human nerve recordings support the hypothesis of a regional alteration in sympathetic impulse pattern following a nerve lesion. The implications of this phenomenon for pain conditions remains to be explored; our patients did not suffer from phantom or stump pain.

Process, mechanism, and explanation related to externalizing behavior in developmental psychopathology.

Advances in conceptualization and statistical modeling, on the one hand, and enhanced appreciation of transactional pathways, gene-environment correlations and interactions, and moderator and mediator variables, on the other, have heightened awareness of the need to consider factors and processes that explain the development and maintenance of psychopathology. With a focus on attentional problems, impulsivity, and disruptive behavior patterns, I address the kinds of conceptual approaches most likely to lead to advances regarding explanatory models in the field. Findings from my own research program on processes and mechanisms reveal both promise and limitations. Progress will emanate from use of genetically informative designs, blends of variable and person-centered research, explicit testing of developmental processes, systematic approaches to moderation and mediation, exploitation of "natural experiments," and the conduct of prevention and intervention trials designed to accentuate explanation as well as outcome. In all, breakthroughs will occur only with advances in translational research-linking basic and applied science-and with the further development of transactional, systemic approaches to explanation.

Pain and the Neuromatrix in the Brain

The neuromatrix theory of pain proposes that pain is a multidimensional experience produced by characteristic "neurosignature" patterns of nerve impulses generated by a widely distributed neural network-the "body-self neuromatrix"-in the brain. These neurosignature patterns may be triggered by sensory inputs, but they may also be generated independently of them. Acute pains evoked by brief noxious inputs have been meticulously investigated by neuroscientists, and their sensory transmission mechanisms are generally well understood. In contrast, chronic pain syndromes, which are often characterized by severe pain associated with little or no discernible injury or pathology, remain a mystery. Furthermore, chronic psychological or physical stress is often associated with chronic pain, but the relationship is poorly understood. The neuromatrix theory of pain provides a new conceptual framework to examine these problems. It proposes that the output patterns of the body-self neuromatrix activate perceptual, homeostatic, and behavioral programs after injury, pathology, or chronic stress. Pain, then, is produced by the output of a widely distributed neural network in the brain rather than directly by sensory input evoked by injury, inflammation, or other pathology. The neuromatrix, which is genetically determined and modified by sensory experience, is the primary mechanism that generates the neural pattern that produces pain. Its output pattern is determined by multiple influences, of which the somatic sensory input is only a part, that converge on the neuromatrix.

Calcineurin controls nerve activity-dependent specification of slow skeletal muscle fibers but not muscle growth.

Nerve activity can induce long-lasting, transcription-dependent changes in skeletal muscle fibers and thus affect muscle growth and fiber-type specificity. Calcineurin signaling has been implicated in the transcriptional regulation of slow muscle fiber genes in culture, but the functional role of calcineurin in vivo has not been unambiguously demonstrated. Here, we report that the up-regulation of slow myosin heavy chain (MyHC) and a MyHC-slow promoter induced by slow motor neurons in regenerating rat soleus muscle is prevented by the calcineurin inhibitors cyclosporin A (CsA), FK506, and the calcineurin inhibitory protein domain from cain/cabin-1. In contrast, calcineurin inhibitors do not block the increase in fiber size induced by nerve activity in regenerating muscle. The activation of MyHC-slow induced by direct electrostimulation of denervated regenerating muscle with a continuous low frequency impulse pattern is blocked by CsA, showing that calcineurin function in muscle fibers and not in motor neurons is responsible for nerve-dependent specification of slow muscle fibers. Calcineurin is also involved in the maintenance of the slow muscle fiber gene program because in the adult soleus muscle, cain causes a switch from MyHC-slow to fast-type MyHC-2X and MyHC-2B gene expression, and the activity of the MyHC-slow promoter is inhibited by CsA and FK506.

Noise-induced impulse pattern modifications at different dynamical period-one situations in a computer model of temperature encoding

We used a minimal Hodgkin–Huxley type model of cold receptor discharges to examine how noise interferes with the non-linear dynamics of the ionic mechanisms of neuronal stimulus encoding. The model is based on the assumption that spike-generation depends on subthreshold oscillations. With physiologically plausible temperature scaling, it passes through different impulse patterns which, with addition of noise, are in excellent agreement with real experimental data. The interval distributions of purely deterministic simulations, however, exhibit considerable differences compared to the noisy simulations especially at the bifurcations of deterministically period-one discharges. We, therefore, analyzed the effects of noise in different situations of deterministically regular period-one discharges: (1) at high-temperatures near the transition to subthreshold oscillations and to burst discharges, and (2) at low-temperatures close to and more far away from the bifurcations to chaotic dynamics. The data suggest that addition of noise can considerably extend the dynamical behavior of the system with coexistence of different dynamical situations at deterministically fixed parameter constellations. Apart from well-described coexistence of spike-generating and subthreshold oscillations also mixtures of tonic and bursting patterns can be seen and even transitions to unstable period-one orbits seem to appear. The data indicate that cooperative effects between low- and high-dimensional dynamics have to be considered as qualitatively important factors in neuronal encoding.

Transmission security for single, hair follicle-related tactile afferent fibers and their target cuneate neurons in cat.

Transmission from single, identified hair follicle afferent (HFA) nerve fibers to their target neurons of the cuneate nucleus was examined in anesthetized cats by means of paired recording from individual cuneate neurons and from fine, intact fascicles of the lateral branch of the superficial radial nerve in which it is possible to identify and monitor the activity of each group II fiber. Selective activation of individual HFA fibers was achieved by means of focal vibrotactile skin stimulation. Forearm denervation precluded inputs from sources other than the monitored HFA sensory fiber. Transmission characteristics were analyzed for 21 HFA fiber-cuneate neuron pairs in which activity in the single HFA fiber of each pair reliably evoked spike output from the target neuron at a fixed latency. As the cuneate responses to each HFA impulse often consisted of 2 or 3 spikes, in particular at HFA input rates up to approximately 20 imp/s, the synaptic linkage displayed potent amplification and high-gain transmission, characteristics that were confirmed quantitatively in measures of transmission security and cuneate spike output measures. In response to vibrotactile stimuli, the tight phase locking in the responses of single HFA fibers was well retained in the cuneate responses for vibration frequencies up to approximately 200 Hz. On measures of vector strength, the phase locking declined across the synaptic linkage by no more than approximately 10% at frequencies up to 100 Hz. However, limitations on the impulse rates generated in both the HFA fibers their associated cuneate neurons meant that the impulse patterns could not directly signal information about the vibration frequency above 50-100 Hz. Although single HFA fibers are also known to have secure synaptic linkages with spinocervical tract neurons, it is probable that this linkage lacks the capacity of the HFA-cuneate synapse for conveying precise temporal information, in an impulse pattern code, about the frequency parameter of vibrotactile stimuli.

Historical Perspectives: plasticity of mammalian skeletal muscle.

More than 40 years ago, the nerve cross-union experiment of Buller, Eccles, and Eccles provided compelling evidence for the essential role of innervation in determining the properties of mammalian skeletal muscle fibers. Moreover, this experiment revealed that terminally differentiated muscle fibers are not inalterable but are highly versatile entities capable of changing their phenotype from fast to slow or slow to fast. With the use of various experimental models, numerous studies have since confirmed and extended the notion of muscle plasticity. Together, these studies demonstrated that motoneuron-specific impulse patterns, neuromuscular activity, and mechanical loading play important roles in both the maintenance and transition of muscle fiber phenotypes. Depending on the type, intensity, and duration of changes in any of these factors, muscle fibers adjust their phenotype to meet the altered functional demands. Fiber-type transitions resulting from multiple qualitative and quantitative changes in gene expression occur sequentially in a regular order within a spectrum of pure and hybrid fiber types.

Golgi Complex, Endoplasmic Reticulum Exit Sites, and Microtubules in Skeletal Muscle Fibers Are Organized by Patterned Activity

The Golgi complex of skeletal muscle fibers is made of thousands of dispersed elements. The distributions of these elements and of the microtubules they associate with differ in fast compared with slow and in innervated compared with denervated fibers. To investigate the role of muscle impulse activity, we denervated fast extensor digitorum longus (EDL) and slow soleus (SOL) muscles of adult rats and stimulated them directly with patterns that resemble the impulse patterns of normal fast EDL (25 pulses at 150 Hz every 15 min) and slow SOL (200 pulses at 20 Hz every 30 sec) motor units. After 2 weeks of denervation plus stimulation, peripheral and central regions of muscle fibers were examined by immunofluorescence microscopy with regard to density and distribution of Golgi complex, microtubules, glucose transporter GLUT4, centrosomes, and endoplasmic reticulum exit sites. In extrajunctional regions, fast pattern stimulation preserved normal fast characteristics of all markers in EDL type IIB/IIX fibers, although inducing changes toward the fast phenotype in originally slow type I SOL fibers, such as a 1.5-fold decrease of the density of Golgi elements at the fiber surface. Slow pattern stimulation had converse effects such as a 2.2-fold increase of the density of Golgi elements at the EDL fiber surface. In junctional regions, where fast and slow fibers are similar, both stimulation patterns prevented a denervation-induced accumulation of GLUT4. The results indicate that patterns of muscle impulse activity, as normally imposed by motor neurons, play a major role in regulating the organization of Golgi complex and related proteins in the extrajunctional region of muscle fibers.

Respiratory-related neuronal activity in the nucleus ambiguus-retroambigualis complex and their responses to peripheral and central stimulation in the rat

This study aimed to locate respiratory-related neurons in NA/NRA complex within the ventrolateral medulla (VLM), characterise them, and study their responses to the stimulation of midbrain periaque-ductal gray matter (PAG) and vagal afferents. Stereotactic mapping of the medullary NA/NRA complex using stainless steel microelectrodes was undertaken in Nembutal-anaesthetised (80 mg/kg), spontaneously-breathing rats (n = 60, 300-400 g). Individual cells and cell populations showing respiratory-related firing patterns were recorded along the VLM, 2.5 mm rostral -2.1 mm caudal to the obex, 1.4-2.2 mm lateral to midline and 1.5-3.00 mm below dorsal medullary surface. The cells were classified according to their temporal relationship with the diaphragm electromyogram (dEMG). Early inspiratory cells (eIcells) were found to start firing up to 20 ms before dEMG activity and to cease activity through mid-inspiration, exhibiting a decrementing discharge pattern. Late inspiratory (lateI) cells commenced their activity midway through inspiration and stopped firing prior to the cessation of dEMG. These cells exhibited an incrementing discharge pattern. Cells firing in phase with the dEMG have been classified as I-all cells and exhibit a steady impulse pattern throughout inspiration. Neurons active during the expiratory phase have been categorised as early expiratory cells (earlyE), late expiratory cells (lateE) and E-all neurons according to their discharge pattern in relation to dEMG. Cells in the dorso-lateral PAG were activated with microinjections of excitatory amino acid D,L-homocysteic acid (DLH0.2 M, 10-60 nl) and VLM respiratory neuronal and muscle responses were studied. PAG stimulation induced dose-dependent changes to respiratory output. Inspiratory and expiratory durations were shortened, respiratory frequency and dEMG activity increased along with increases in heart rate and blood pressure. Concurrently PAG stimulation led to increased activation of eI cells, I-all cells and E-all cells found in the NA/NRA complex. Abdominal muscle activity was not evident during quiet breathing though expiratory neuronal activity was seen. However, activation of PAG elicited synchronous aEMG bursts along with an increase in E-all cell activity. Unilateral vagal nerve stimulation, in order to simulate activation of the pulmonary stretch receptors, was undertaken. I-all cell and dEMG activity were inhibited upon stimulation of the vagus. However, I-all neuronal firing as well as the diaphragm activity resurfaced whilst vagal stimulation was prolonged. Expiratory cells are yet to be tested for responses to vagal stimulation. Our previous studies [1] demonstrated a physiological link between the PAG and NTS in the rat. The current investigation shows that chemical activation of PAG influences the discharge patterns of the VLM respiratory neurons within the NA/NRA complex suggesting a possible physiological link between the two centres. These results indicate that both NTS and NA/NRA respiratory neurons participate in the mediation of PAG induced respiratory changes. Roles for NA/NRA neurons in the brainstem control of respiration in the rat and the interactions between the neural centres in the midbrain are discussed.

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Ground Reaction Force Pattern in Limbs with Intermittent Claudication

Objectives: to investigate the presence of a ground reaction force pattern specific to the patient with unilateral intermittent claudication (IC), and the relationship of this pattern with onset of claudication.Design: identification of impulse pattern during gait of lower limbs with and without ischaemia, in patients with unilateral IC and controls. Methods: thirty patients with unilateral IC and six peripheral arterial disease non-claudicant patients had their gait recorded using the F-Scan system during a treadmill test. Their plantar impulse pattern was calcuated. Examined lower limbs were subdivided into groups: ischaemic limbs (30), contralateral limbs (30) and lower limbs of patients without IC (12). Two impulse patterns were found: the descending one, where impulse values decrease during gait, and the non-descending one, where these values do not decrease during gait. The numerical distribution of patterns among limb groups was determined and their ratios compared. Correlation between claudication onset and impulse pattern was also investigated.Results: most ischaemic limbs exhibited a descending pattern, in contrast with control and contralateral non-ischaemic limbs (p<0.02). There was no relationship between impulse pattern and claudication onset. Conclusions: ischaemic lower limbs present the descending pattern of plantar impulse. No relationship exists between this pattern and claudication pain.

Interactions between slow and fast conductances in the Huber/Braun model of cold-receptor discharges

Transitions between different types of impulse patterns, according to experimentally recorded cold-receptor discharges, can successfully be mimicked with a minimal Hodgkin–Huxley-type simulation, here referred to as the Huber/Braun cold-receptor model. The model consists of two sets of simplified de- and repolarizing ionic conductances responsible for spike generation and slow-wave potentials, respectively. Over a broad temperature range, spike patterns are determined by the periodicity of subthreshold oscillations. At low temperatures, however, the periodicity of the pattern is destroyed and then appears again but with different patterns of different rhythmicity. We demonstrate that these complex transitions originate from the interactions between slow-wave and spike-generating currents.

Stochastic encoding in sensory neurons: impulse patterns of mammalian cold receptors

Intrinsic oscillations at the level of the membrane potential are a widespread feature of nerve cells. Several evidences exist that, in particular, sensory neurons combine their oscillatory membrane potentials with intrinsic, membrane and/or synaptic noise to obtain sensitive encoding properties. An interesting example are mammalian cold receptors where stimulus transduction results from modulation of intrinsic receptor oscillations with essential contribution of noise thereby generating a rich spectrum of impulse patterns. To further explore the dynamics of these receptors we here investigate an HH-type model for oscillations and spike initiation in cold receptors. By use of a biophysically plausible temperature scaling and with addition of noise, the model successfully mimicks the principle temperature-dependence of stationary impulse patterns of real cold receptors. Our results suggest that interactions between stochastic and deterministic dynamics are of functional importance for the encoding charcteristics of cold receptors.

Phasic bursting activity of paraventricular neurons is modulated by temperature and angiotensin II

1. Impulse activity of phasically firing (bursting) paraventricular neurons, which are assumed to be of the vasopressinergic type, have been extracellularly recorded in brain slices of the rat. 2. Analysis of burst patterns during temperature changes, angiotensin II application and combined application of both stimuli demonstrated that certain burst parameters are effected much stronger than the mean firing rate and also for a longer period of time. 3. The most sensitive parameter was the intraburst frequency which is considered to be the most effective parameter for increased vasopressin release. 4. These data indicate that there are functionally relevant changes in the impulse patterns which are not necessarily manifested in the mean firing rate.

Pain--an overview.

The neuromatrix theory of pain proposes that pain is a multidimensional experience produced by characteristic "neurosignature" patterns of nerve impulses generated by a widely distributed neural network--the "body-self neuromatrix"--in the brain. These neurosignature patterns may be triggered by sensory inputs, but they may also be generated independently of them. Pains that are evoked by noxious sensory inputs have been meticulously investigated by neuroscientists, and their sensory transmission mechanisms are generally well understood. In contrast, chronic pain syndromes, which are often characterized by severe pain associated with little or no discernible injury or pathology, remain a mystery. The neuromatrix theory of pain, however, provides a new conceptual framework that is consistent with recent clinical evidence. It proposes that the output patterns of the neuromatrix activate perceptual, homeostatic and behavioral programs after injury or pathology, or as a result of multiple other inputs that act on the neuromatrix. Pain, then, is produced by the output of a widely distributed neural network in the brain rather than directly by sensory input evoked by injury, inflammation or other pathology. The neuromatrix, which is genetically determined and modified by sensory experience, is the primary mechanism that generates the neural pattern that produces pain. Its output pattern is determined by multiple influences, of which the somatic sensory input is only a part, that converge on the neuromatrix.

From the gate to the neuromatrix

The gate control theory's most important contribution to understanding pain was its emphasis on central neural mechanisms. The theory forced the medical and biological sciences to accept the brain as an active system that filters, selects and modulates inputs. The dorsal horns, too, were not merely passive transmission stations but sites at which dynamic activities (inhibition, excitation and modulation) occurred. The great challenge ahead of us is to understand brain function. I have therefore proposed that the brain possesses a neural network — the body-self neutromatrix — which integrates multiple inputs to produce the output pattern that evokes pain. The body-self neuromatrix comprises a widely distributed neural network that includes parallel somatosensory, limbic and thalamocortical components that subserve the sensory-discriminative, affective-motivational and evaluative-cognitive dimensions of pain experience. The synaptic architecture of the neuromatrix is determined by genetic and sensory influences. The ‘neurosignature’ output of the neuromatrix — patterns of nerve impulses of varying temporal and spatial dimensions — is produced by neural programs genetically build into the neuromatrix and determines the particular qualities and other properties of the pain experience and behavior. Multiple inputs that act on the neuromatrix programs and contribute to the output neurosignature include, (1) sensory inputs (cutaneous, visceral and other somatic receptors); (2) visual and other sensory inputs that influence the cognitive interpretation of the situation; (3) phasic and tonic cognitive and emotional inputs from other areas of the brain; (4) intrinsic neural inhibitory modulation inherent in all brain function; (5) the activity of the body's stress-regulation systems, including cytokines as well as the endocrine, autonomic, immune and opioid systems. We have traveled a long way from the psychophysical concept that seeks a simple one-to-one relationship between injury and pain. We now have a theoretical framework in which a genetically determined template for the body-self is modulated by the powerful stress system and the cognitive functions of the brain, in addition to the traditional sensory inputs.