Rhythmic cortical activity and its relation to the neurogenic components of normal and pathological tremors.
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Cerebral Cortex↗
Biomedical subjects
B A Conway
Publications and source records attributed to B A Conway.
Load-independent contributions from motor-unit synchronization to human physiological tremor.
This study describes two load-independent rhythmic contributions from motor-unit synchronization to normal physiological tremor, which occur in the frequency ranges 1-12 Hz and 15-30 Hz. In common with previous studies, we use increased inertial loading to identify load-independent components of physiological tremor. The data consist of simultaneous recordings of tremor acceleration from the third finger, a surface electromyogram (EMG), and the discharges of pairs of single motor units from the extensor digitorum communis (EDC) muscle, collected from 13 subjects, and divided into 2 data sets: 106 records with the finger unloaded and 84 records with added mass from 5 to 40 g. Frequency domain analysis of motor-unit data from individual subjects reveals the presence of two distinct frequency bands in motor-unit synchronization, 1-12 Hz and 15-30 Hz. A novel Fourier-based population analysis demonstrates that the same two rhythmic components are present in motor-unit synchronization across both data sets. These frequency components are not related to motor-unit firing rates. The same frequency bands are present in the correlation between motor-unit activity and tremor and between surface EMG activity and tremor, despite a significant alteration in the characteristics of the tremor with increased inertial loading. A multivariate analysis demonstrates conclusively that motor-unit synchronization is the source of these contributions to normal physiological tremor. The population analysis suggests that single motor-unit discharges can predict an average of 10% of the total tremor signal in these two frequency bands. Rectified surface EMG can predict an average of 20% of the tremor; therefore within our population of recordings, the two components of motor-unit synchronization account for an average of 20% of the total tremor signal, in the frequency ranges 1-12 Hz and 15-30 Hz. Our results demonstrate that normal physiological tremor is a complex signal containing information relating to motor-unit synchronization in different frequency bands, and lead to a revised definition of normal physiological tremor during low force postural contractions, which is based on using both the tremor spectra and the correlation between motor-unit activity and tremor to characterize the load-dependent and the load-independent components of tremor. In addition, both physiological tremor and rectified EMG emerge as powerful predictors of the frequency components of motor-unit synchronization.
Adult↗
Activity of abundant antimicrobials of the human airway.
Human airways produce several antimicrobial factors; the most abundant are lysozyme and lactoferrin. Despite their likely importance in preventing infection, and their possible key role in the pathogenesis of cystic fibrosis (CF), we know little about their antibacterial activity in the context of the CF airway. We found that abundant airway antimicrobial factors kill common CF pathogens, although Burkholderia was relatively resistant. To study the antibacterial activity, we developed a rapid, sensitive, and quantitative in vitro luminescence assay. Because NaCl concentrations may be elevated in CF airway surface liquid, we tested the effect of salt on antibacterial activity. Activity of individual factors and of airway lavage fluid was inhibited by high ionic strength, and it was particularly sensitive to divalent cations. However, it was not inhibited by nonionic osmolytes and thus did not require hypotonic liquid. The inhibition by ionic strength could be partially compensated by increased concentrations of antibacterial factors, thus there was no one unique salt concentration for inhibition. CF airway secretions also contain abundant mucin and elastase; however, these had no effect on antibacterial activity of lysozyme, lactoferrin, or airway lavage fluids. When studied at low NaCl concentrations, CF and non-CF airway lavage fluids contained similar levels of antibacterial activity. These results suggest approaches toward developing treatments aimed at preventing or reducing airway infections in individuals with CF.
Anti-Infective Agents↗
Production of beta-defensins by human airway epithelia.
Human beta-defensins (HBDs) are antimicrobial peptides that may play a role in mucosal defense. Diminished activity of these peptides has been implicated in the pathogenesis of cystic fibrosis (CF) lung disease. We show that HBD-1 and HBD-2 mRNAs are expressed in excised surface and submucosal gland epithelia from non-CF and CF patients. The pro-inflammatory cytokine interleukin-1beta stimulated the expression of HBD-2 but not HBD-1 mRNA and peptide in primary cultures of airway epithelia. HBD-1 was found in bronchoalveolar lavage (BAL) fluid from normal volunteers, CF patients, and patients with inflammatory lung diseases, whereas HBD-2 was detected in BAL fluid from patients with CF or inflammatory lung diseases, but not in normal volunteers. Both HBD-1 and HBD-2 were found in BAL fluid in concentrations of several ng/ml, and both recombinant peptides showed salt-sensitive bactericidal activity. These data suggest that in the lung HBD-2 expression is induced by inflammation, whereas HBD-1 may serve as a defense in the absence of inflammation.
Cells, Cultured↗
How do we approach the locomotor network in the mammalian spinal cord?
For a large number of vertebrate species it is now indisputable that spinal networks have the capability of generating the basic locomotor rhythm. However, because of technical difficulties, the rate of progress in defining the intrinsic properties of mammalian locomotor rhythm generators has been slow in comparison to that made in the study of such networks in lower vertebrates. Investigations on afferent and descending control of locomotor activity in mammals have demonstrated that many of these pathways interact with the rhythm generator. In this review we discuss how these interactions (resetting) can be used for outlining relevant spinal circuits as a basis for a future identification of individual neurons of the spinal locomotor networks. In this overview we have given particular emphasis to selected afferent systems to illustrate the possibilities and problems with this approach.
Animals↗
Identification of patterns of neuronal connectivity--partial spectra, partial coherence, and neuronal interactions.
The cross-correlation histogram has provided the primary tool for inferring the structure of common inputs to pairs of neurones. While this technique has produced useful results it not clear how it may be extended to complex networks. In this report we introduce a linear model for point process systems. The finite Fourier transform of this model leads to a regression type analysis of the relations between spike trains. An advantage of this approach is that the full range of techniques for multivariate regression analyses becomes available for spike train analysis. The two main parameters used for the identification of neural networks are the coherence and partial coherences. The coherence defines a bounded measure of association between two spike trains and plays the role of a squared correlation coefficient defined at each frequency lambda. The partial coherences, analogous to the partial correlations of multiple regression analysis, allow an assessment of how any number of putative input processes may influence the relation between any two output processes. In many cases analytic solutions may be found for coherences and partial coherences for simple neural networks, and in combination with simulations may be used to test hypotheses concerning proposed networks inferred from spike train analyses.
Animals↗
Using electroencephalography to study functional coupling between cortical activity and electromyograms during voluntary contractions in humans.
Previous studies of neuronal oscillations in sensorimotor cortex in humans and primates have observed rhythmic 15-30 Hz activity, which is correlated with motor output. In humans, this work has been limited to magnetic recordings. In the present study we investigate if similar results can be obtained using electroencephalography (EEG). EEG recordings were made from over the sensorimotor cortex of five adult subjects who performed repeated periods of maintained wrist extension and flexion. Coherence analysis between EEG and electromyogram (EMG) recordings from these muscles revealed correlation in the 15-30 Hz range, with a synchronous correlation structure which matches that previously observed in humans and in paired cortical recordings from primates. We conclude that EEG is equally efficient at investigating functional aspects of these cortical rhythms during voluntary movement in humans.
Adult↗
Abnormal motor unit synchronization of antagonist muscles underlies pathological co-contraction in upper limb dystonia.
The aim of this study was to examine the pathophysiological mechanisms underlying co-contraction in patients with dystonia (n = 6) and writer's cramp (n = 5). Multi-unit needle and surface EMGs were recorded from extensor carpi radialis (ECR) and flexor carpi radialis (FCR) muscles during motor tasks that elicited dystonia or writer's cramp. The EMGs from ECR and FCR were recorded simultaneously and analysed using cross-correlation analysis. Similar recordings were obtained from healthy age- and sex-matched control subjects (n = 8). Despite co-contraction of the muscles, cross-correlograms from the healthy subjects did not reveal evidence of motor unit synchronization. Cross-correlograms from the dystonic subjects revealed a central peak with a median duration of 37 ms, indicating broad-peak motor unit synchronization. Cross-correlograms from patients with writer's cramp were either flat or modulated by a 11-12-Hz tremor. Frequency-domain analysis of ECR and FCR EMGs demonstrated significant coherence in the patients with dystonia and writer's cramp. These results indicate that co-contraction in dystonia is neurophysiologically distinct from voluntary co-contraction and is produced by abnormal synchronization of presynaptic inputs to antagonist motor neuron pools. ECR and FCR co-contraction in writer's cramp may be a compensatory process under voluntary control.
Adolescent↗
A review of recent applications of cross-correlation methodologies to human motor unit recording.
This article reviews some recent applications of time and frequency domain cross-correlation techniques to human motor unit recording. These techniques may be used to examine the pre-synaptic mechanisms involved in control of motoneuron activity during on-going motor tasks in man without the need for imposed and artificial perturbations of the system. In this review we examine, through several examples, areas in which insights have been gained into the basic neurophysiological processes that bring about motoneuron firing in man and illustrate how these processes are affected by central nervous system pathology. We will demonstrate that synchronization and coherence may be revealed between human motor unit discharges and give examples that support the hypothesis that these phenomena are generated by activity in a focused common corticospinal input to spinal motoneurons. Disruption of central motor pathways due to diseases of the nervous system leads to pathophysiological alterations in the activity of these pre-synaptic motoneuron inputs that can be revealed by cross-correlation analysis of motor unit discharges. The significance of these studies and outstanding questions in this field are discussed.
Electromyography↗
An extended difference of coherence test for comparing and combining several independent coherence estimates: theory and application to the study of motor units and physiological tremor.
Recently there has been an increase in the use of spectral methods for the analysis of experimental data. These analytical methods allow the study of interactions between simultaneously recorded signals and are particularly suited to the study of systems displaying rhythmic behaviour. A useful parameter in this context is the coherence function which provides a bounded measure of linear association between two signals. In this report we introduce two new techniques for dealing with an arbitrary number of independent coherence estimates. The first technique provides a test to compare the coherence estimates for statistically significant differences. The second allows the original coherence estimates to be combined, or 'pooled' into a single representative estimate. These two measures, taken together, provide a powerful tool for characterising and summarising the correlations within data sets. Applications of the techniques are illustrated by analysing the interactions between single motor unit discharges and finger tremor, and between pairs of motor unit discharges in human subjects.
Humans↗
Synchronization between motor cortex and spinal motoneuronal pool during the performance of a maintained motor task in man.
1. Simultaneous recordings of cortical activity, recorded as the magnetoencephalogram (MEG), and the electromyogram (EMG) of the ipsilateral and contralateral first dorsal interosseous muscles (1DI) were made during maintained voluntary contractions. 2. The MEG recorded from a localized region of the sensorimotor cortex of the dominant hemisphere was coherent with the EMG from the contralateral 1DI muscle over a limited band of frequencies. The peak coherence was confined largely within the beta range of cortical activity (13-35 Hz). Significant cortical activity at 10 Hz and 40-50 Hz was not correlated with motor output. The MEG and EMG from the ipsilateral 1DI muscle were uncorrelated at all frequencies. 3. Significant coherence between the MEG and the EMG was associated with synchronous behaviour between the MEG and EMG in the time domain. 4. The results demonstrate that synchronized cortical activity contributing to MEG activity within the beta range of frequencies during maintained voluntary contractions is coupled to motor output at frequencies of motor-unit activity associated with motor-unit synchronization. This observation provides further evidence for the involvement of cortical neurones in the generation of motor-unit synchronization. 5. We suggest that the coherence between MEG and contralateral EMG observed during maintained isometric contractions may provide an example of binding within the motor system.
Adult↗
A framework for the analysis of mixed time series/point process data--theory and application to the study of physiological tremor, single motor unit discharges and electromyograms.
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Biophysical Phenomena↗
Detection of weak synaptic interactions between single Ia afferent and motor-unit spike trains in the decerebrate cat.
1. Spike trains from identified single Ia afferents from soleus and lateral gastrocnemius muscles were recorded (while 'in continuity' with the spinal cord) simultaneously with single-motor-unit EMG spike trains from the same muscles in decerebrate cats. 2. A total of 143 Ia afferent-motor-unit pairs were examined for the presence of correlated activity between the Ia afferent and motor-unit and between the motor-unit and Ia afferent. Four types of correlation were identified on the basis of the cross-intensity function estimated for individual Ia afferent-motor-unit pairs. These correlations were attributed to the absence or presence of a central Ia afferent-motoneurone interaction or a peripheral motor-unit-muscle spindle interaction. 3. In addition to the cross-correlation-based second-order cross-intensity function, third-order cumulants were defined and used further to investigate Ia afferent-motor-unit interactions. A third-order cumulant density-based approach to signal processing offers improved signal-to-noise ratios, compared with the traditional product density approach, for parameters characterizing certain kinds of linear processes as well as a description of non-linear interactions. Two classes of third-order relations were described. One class was associated with a strong central connection and the other with a weak central connection. 4. Third-order cumulants estimated for Ia afferent-motor-unit pairs with significant second-order central correlations were able to detect a period of decreased motoneuronal excitability. In addition, temporal summation prior to spike initiation could be identified in cases where the afferent discharge was suitably high. 5. Third-order cumulants estimated for Ia afferent-motor-unit pairs in which no significant second-order central correlation existed identified the presence of weak synaptic interactions. It is argued that these interactions result from the summation from the recorded Ia afferent discharge and other spontaneous synaptic inputs to the motoneurone. 6. The results of the second-order cross-intensity analysis of Ia afferent-motor-unit interactions, combined with those from the third-order cumulant density analysis, showed that 77% of the recorded afferents had a detectable influence on motor-unit behaviour. 7. The results of this study suggest that the third-order cumulant, based on the analysis of spike trains, will provide a useful tool for detecting synaptic interactions not found by the use of the second-order cross-correlation histogram alone, and may also be used to estimate the time course of post-spike depression in motoneurones, as well as other non-linear regions of motoneurone membrane trajectory.
Action Potentials↗
Toward effective customer-supplier relationships.
Baxter Healthcare Corporation, a worldwide supplier to hospitals, has been using the principles of total quality management to improve their products and services as well as reshape relationships with customers. This article enumerates what suppliers and hospitals need in order to make mutually beneficial relationships possible and presents three examples of Baxter's work in this area.
Consumer Behavior↗
Spinal locomotor activity in acutely spinalized cats induced by intrathecal application of noradrenaline.
In this study we present a method of intrathecal drug administration in the acute spinal cat. A thin tube introduced into the subarachnoid space below the spinal cord was used for local drug administration. Noradrenaline reduced short-latency and provoked long-latency reflexes following high threshold afferent stimulation. Topical application of noradrenaline to the spinal cord was also able to induce and maintain locomotion. Our results strengthen the notion that noradrenergic systems play an important role in motor control. In addition, the present report introduces a protocol in the acute spinal cat, which combine the benefits associated with direct application of drugs as used in vitro experiments with the advantages of using the well investigated in vivo cat spinal cord preparation.
Animals↗
In vitro effects of dihydrotestosterone on granulosa cell production of estrogen and progesterone.
To investigate the direct effects of androgens on follicle development, intact, immature female rats were given 8 IU PMSG (0 hour) and four injections of either vehicle or dihydrotestosterone (DHT), 1 mg/kg body weight, at 0, 12, 24, and 36 hours after PMSG. Granulosa cells from small (less than 200 microns), medium (200 to 400 microns), and large (greater than 400 microns) follicles were isolated and cultured in the presence or absence of 0.5 microM DHT in vitro for 48 hours, and the medium was assayed for progesterone and estrogen. Results show that DHT caused an increase in progesterone accumulation in all granulosa cells, regardless of follicle size. However, DHT inhibited estrogen accumulation in granulosa cells from different-size follicles and the inhibition varied depending on the duration of androgen exposure in vivo. The inhibition of estrogen accumulation was seen in granulosa cells from small follicles without prior exposure to DHT in vivo, while an inhibition of estrogen accumulation was seen in granulosa cells from medium and large follicles exposed to DHT treatment in vivo. Taken together, the results of experiments with in vivo and/or in vitro DHT treatment show that the androgen increases granulosa cell progesterone synthesis regardless of follicle size. However, the estrogen accumulation by granulosa cell is dependent on follicle size and duration of DHT exposure.
Animals↗
Flow cytometric analysis of granulosa cells from developing rat follicles.
Immature rats were treated with diethylstilboestrol (DES) or pregnant mares' serum gonadotropin (PMSG) and forward angle light-scatter (FALS) and 90 degrees light-scatter (90 degrees LS) signals were used to measure the size and the granularity (internal organization) of the granulosa cells, respectively. The results confirmed the presence of two major populations of granulosa cells in the ovaries of both groups of rats, with the same percentage of larger cells in both treatments (52.3% in DES, 49.5% in PMSG). Since DES treatment brings about granulosa cell growth while PMSG treatment causes growth and differentiation, it is evident that there is heterogeneity in granulosa cell sizes during different states of growth and differentiation. There was also heterogeneity in sizes of granulosa cells harvested from follicles of small (less than 210 microns), medium (210-420 microns) and large (greater than 420 microns) diameter. Quadrant analysis of granulosa cells in various fractions collected from Percoll gradients suggested an increase in granularity in the small and large granulosa cell populations. Cell cycle analysis of small and large granulosa cell populations collected from large follicles of rats treated with PMSG indicated that each population was distributed in G0/G1, S and G2/M phases. These results demonstrate that populations of small and large granulosa cells exist in rat ovarian follicles during various stages of growth and differentiation.
Animals↗
Partners in quality: managing your suppliers.
Just expecting more from your supplier is not what partnership is about. We have had the experience where the quality improvement and partnership banner has been waved but the tone and spirit of the meeting did not encourage or support a joint quality improvement effort. Benefits will not be achieved until the wall truly begins to come apart and the relationship is built on mutual respect and trust. Data collection and open answers to questions often reveal embarrassing errors and obvious needs for improvements. As stated before, blame and finger-pointing must be replaced with a mutual commitment to asking and answering the question, "How can we improve?" As Dr. W. Edwards Deming has stated, "End the practice of awarding business on the basis of price tag. Instead, minimize total cost. Move toward a single supplier for any one item on a long-term relationship of loyalty and trust." The structured approach of a quality improvement process and the application of quality methods and techniques has proven useful in removing emotion and helping the team focus on the process rather than the people and the issues involved. Quality improvement methods are focused on achieving both customer and supplier goals--customer satisfaction, employee satisfaction, and operational efficiency and effectiveness. Our experience with Partners in Quality as well as our experience with the quality leadership process supports a recent quote in the Harvard Business Review: "Quality is not just a slogan...(it is) the most profitable way to run a business."
Commerce↗