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Biomedical subjects

C K Knox

Publications and source records attributed to C K Knox.

11 recordsLinked to original sources

Physiological and clinical correlates of cardiorespiratory reflexes in diabetes mellitus.

Cardiorespiratory reflexes (CRRs) were studied by measuring heart-rate (HR) variation during 6 breaths/min respiration (delta R6) and Valsalva maneuver (VR) in 145 healthy and 417 type I (insulin-dependent) diabetic subjects. HR variation with breathing at 12 breaths/min and ventilatory response to hypercapnia/hypoxia were measured in fewer subjects. CRR results were compared with symptoms of autonomic dysfunction, the neurological examination, nerve conduction studies, and quantitative sweat testing. The objective was to compare the sensitivity of various methods of characterizing diabetic patients and to use this information when staging patients for clinical therapeutic trials. CRR responses were age dependent in both populations. Either delta R6 or VR was abnormal in 74% of diabetic patients, delta R6 being more sensitive. CRRs correlated well with the presence of symptoms of autonomic dysfunction, abnormalities on the neurological examination, results of nerve conduction studies, and sweating activity in the feet of the same patients. However, both CRRs and sweating were abnormal in a high proportion of patients without any clinical manifestations of neuropathy. The ventilatory reflex response to moderate hypercapnia/hypoxia was also measured. It was normal in most of the diabetic patients tested, including many with severe reduction of CRRs. We conclude from the combined results of CRR, ventilatory response, and other studies that the causative factors for abnormal CRR may not be confined to the vagus nerves, and that in most instances, the depressed CRR may be due to a decrease in the efficacy of sensorimotor nerve conduction around the reflex arc.

Adolescent

Conditional cross-interval correlation analyses with applications to simultaneously recorded cerebellar Purkinje neurons.

Two conditional cross-correlation techniques are described for the analysis of two simultaneously recorded neuronal spike trains. The conditional interspike interval histogram describes the distribution of interspike intervals of a neuron conditioned by a preceding spike in another neuron. The conditional cross-interval histogram describes the distribution of cross-intervals of two neurons conditioned by a preceding spike in one of the neurons. These techniques could be used to reveal the temporal coupling in the discharge of two neurons recorded simultaneously. The techniques augment the description of the correlation obtained with conventional cross-correlation measures. When applied to the simple spike discharge of simultaneously recorded cerebellar Purkinje neurons, the methods reveal temporal interactions between neurons that are not readily apparent from conventional cross-correlograms. The patterns observed suggest a tightly coupled, temporal surround-inhibition among nearby Purkinje neurons.

Animals

Types and locations of respiratory-related neurons in lateral tegmental field of cat medulla oblongata.

Extracellular microelectrode recordings were made from a total of 868 neurons in the medullas of cats in regions known to contain high densities of respiratory-related neurons (solitary tract complex, nucleus ambiguus/retroambigualis, lateral tegmental field). Both the discharge patterns and the locations of units were noted and correlated with a recently described substructure of the tegmental field of the cat medulla in which neuronal cell bodies are found associated with sheets of blood vessels supplying the brainstem. The majority of cells were phasically firing (59%) with activity confined to either the inspiratory or the expiratory phase, 21% were tonically firing cells with no discernible respiratory modulation and 20% were silent neurons, responsive to electrical stimulation of the vagus nerves or the dorsolateral pons in the vicinity of nucleus parabrachialis, but not to various respiratory stimuli. Within the solitary tract complex inspiratory discharge patterns were predominant (94%), while in nucleus ambiguus/retroambigualis 26% of the neurons had expiratory patterns with the rest being inspiratory (68%) or tonic (6%). Within the lateral tegmental field, the percentages of inspiratory, expiratory and tonic patterns were 51, 9 and 40%. Thus, inspiratory type patterns were found throughout the medulla, but expiratory patterns were most common in the ambiguus/retroambigualis nuclei. Found within all 3 major regions, but primarily within the lateral tegmental field of the rostral medulla were neurons that discharged with a brief burst at the inspiratory to expiratory phase transition. These cells had properties consistent with the off-switch mechanism: extreme late-inspiratory onset of discharge with the onset time being delayed by lung inflation, peak discharge at or slightly after the peak activity of the diaphragmatic EMG and a discharge rate which was insensitive to lung inflation. Within the lateral tegmental field, where longitudinal sheets of blood vessels running radially with respect to the IVth ventricle have been described, it was found that 85% of the tonically active units and 93% of the respiratory modulated cells were located less than 200 microns from the planes of these sheets. In addition, 87% of the neurons that could be antidromically or synaptically activated from the dorsolateral rostral pons were similarly located.

Animals

Correlation analysis of stimulus-evoked changes in excitability of spontaneously firing neurons.

1. Theoretical expressions for the cross-correlation function are described which relate the output spike train of a neuron to an input spike train. The cross-correlation function is related to a convolution integral of two functions: 1) a waiting-time density, which describes the probability of observing the next succeeding output spike given an arbitrary input; and 2) a conditional output autocorrelation function, which contains information related to the statistical properties of the output spike train itself, and to the carry-over of the effects of an input to subsequent intervals. 2. The primary synaptic effect appears in the cross-correlation function as a distorted version of the derivative of the PSP. Depending on the duration of the evoked excitability change, as compared to the mean output interspike interval, periodicities due to the spontaneous activity of the cell appear to a greater or lesser extent in the cross-correlation. 3. To estimate underlying excitability changes using correlation techniques, one must estimate both the cross- and the conditional output autocorrelation functions. In cases when the excitability changes are short and do not carry forward to subsequent intervals, the more readily estimated unconditional output autocorrelation can be used in place of the conditional correlation.

Animals

A determination of excitability changes in dorsal spinocerebellar tract neurons from spike-train analysis.

1. Responses of DSCT neurons to random electrical stimulation of peripheral nerves of the hindleg at group I intensity were studied using cross-correlation analysis of the output spike train with the stimulus. Three types of response were found: type 1 was due to monosynaptic activation of DSCT cells, type 2 resulted from inhibition of those cells, and type 3 was due to a long-latency excitation that was probably polysynaptic. 2. Most of the units studied responded to stimulation of both proximal and distal flexor and extensor nerves. The extensive convergence of afferent input on DSCT cells is much greater than has been observed previously, with type 2 and type 3 responses totaling 80% of the observed responses. We attribute this to the sensitivity of the analysis in detecting small changes in postsynaptic excitability. 3. The results of the study, particularly the derivation of postsynaptic excitability changes, generally confirm those of earlier work employing intracellular recording. 4. By varying stimulus rate and stimulus intensity in the group 1 range and simulating the resulting correlations, we conclude that excitability changes in DSCT cells are the net result of complex interactions involving excitation and inhibition. A summary of these findings is presented as a model for the minimum circuitry necessary to account for the observed behavior.

Afferent Pathways

Changes in the Breuer-Hering reflexes following rostral pontine lesion.

The lung stretch reflex characteristics of unanesthetized decerebrate cats were determined using servo-controlled lung volume changes before and after bilateral lesion of the dorsolateral rostral pons in the region of nucleus parabrachialis medialis (NPBM). During the inspiratory phase the time-dependent threshold curve for inspiratory inhibition by lung inflation was shifted to larger volumes after lesion with no change in the constant describing its rate of decay. During the expiratory phase the gain of the inflation reflex was found to be increased by lesion, but otherwise to remain qualitatively the same. Deflations during the expiratory phase revealed a prolonged central inhibitory state with reduced rate of decay late in expiration. It is concluded that with intact vagi structures in the region of NPBM constitute but one of at least three sources of inspiratory inhibition, feedback derived from peripheral lung stretch receptors and from caudal pontine or medullary neurons also being involved. It is also concluded that the structures in the vicinity of NPBM affect the switching mechanisms differently during the two phases of the cycle: During inspiration they contribute a tonic threshold lowering input to the inspiratory "off-switch"; whereas, during expiration they provide inspiratory-facilitatory influences late in the phase.

Animals

Cross-correlation functions for a neuronal model.

Cross-correlation functions, R(XY)(t,tau), are obtained for a neuron model which is characterized by constant threshold theta, by resetting to resting level after an output, and by membrane potential U(t) which results from linear summation of excitatory postsynaptic potentials h(t). The results show that: (1) Near time lag tau = 0, R(XY)(t,tau) = f(U) [theta-h(tau), t + tau] {h'(tau) + E(U) [u'(t + tau)]} for positive values of this quantity, where f(U)(u,t) is the probability density function of U(t) and E(U) [u'(t + tau)] is the mean value function of U'(t + tau). (2) Minima may appear in R(XY)(t,tau) for a neuron subjected only to excitation. (3) For large tau, R(XY)(t,tau) is given approximately by the convolution of the input autocorrelation function with the functional of point (1). (4) R(XY)(t,tau) is a biased estimator of the shape of h(t), generally over-estimating both its time to peak and its rise time.

Animals