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Biomedical subjects

W D O'Neill

Publications and source records attributed to W D O'Neill.

15 recordsLinked to original sources

The narcoleptic cognitive pupillary response.

It has been reported that narcoleptics exhibit deficits in short-term memory, list recall, and stimulus frequency estimation compared with control subjects. It is also well-known that pupil dilation during cognitive tasks is a measure of subject attention state. Here we present results from six narcoleptics and six controls, a total of 360 experimental records in which pupillograms were made during cognitive tests, which indicate that narcoleptics begin pupillary dilations at a smaller diameter, begin dilating earlier poststimulus, attain higher pupillary diameter velocities, yet achieve the same equilibrium dilation diameter as controls. These findings are derived from statistical tests performed on the parameters of a nonlinear regression model of pupillary cognitive dilation as a function of time. In our experiments, the standard 1-s interdigit time between cognitive stimuli was increased to 2.3 s, which yielded pupillographic time records showing that the process of short-term memory overload sets in gradually at about four memory digits for controls and three memory digits for narcoleptics. We suggest our results can be partially explained by a narcoleptic stimulus-encoding deficit, which limits the time available for subjects to rehearse cognitive tasks. However, we also report the unexpected finding that the inferred encoding deficit is a transient one in that repeated tasks at the same memory load elicit a near normal naroleptic pupillary dilation.

Adult↗

Neurologial interpretations and the information in the cognitive pupillary response.

It has been known for 70 years that the human pupil dilates when a person responds to a cognitive task. Further, it is known that parasympathetic pupillary innervation decreases with raised attention state while sympathetic innervation increases. But the information the pupil transmits during elevated attention states about such neurological dynamics and a quantitative measure of this information have defied statistical modelling. Now we describe experiments using a short-term memory task called an acoustic impulse test in which the pupillary dynamics in response to random acoustic impulses are recorded with a high resolution (0.01 mm) pupillometer with the result that parasympathetic and sympathetic pupillary dilation components are quantifiable, as is the information transmitted by these components.

Arousal↗

Pupil noise is a discriminator between narcoleptics and controls.

The pupil light reflex has a long history of being able to indicate states of mental arousal, ranging from sleepiness to concentrated cognitive effort. Such mental states have usually been inferred from pupil diameter or pupil area movements relative to some reference; sleepiness, for example, is characterized by a smaller than average pupil while mental effort brings on a slightly larger pupil. But all pupil movements and associated states of arousal are accompanied by a persistent random pupil diameter motion which has previously been attributed to neurological noise, the noise apparently arising in the neurological controller of the pupil reflex control system. Our experiments and signal processing methods show that the amplitude of this pupil noise is an indicator of the sleeping disorder narcolepsy. Narcoleptics are found to have diminished pupil noise amplitudes relative to control subjects. Pupil noise is estimated by statistical procedures which yield unbiased noise measures in the form of six-dimensional Gaussian vectors. Each subject is associated with a Gaussian vector which is optimally projected onto a scalar axis so as to maximize the mean square distance between the narcoleptic and control samples. The Kullback-Leibler discrimination function is estimated and then evaluated for each projection as a means of discriminating narcoleptics from controls. The projected noise measures correctly classify 18 out of 20 subjects. The projected values also form the basis for supporting or rejecting a hypothesis of narcoleptic or control class membership. Parametric and nonparametric hypothesis tests suggest that, with probabilities close to one, narcoleptics and controls are distinguishable classes. To emphasize the importance of pupil noise as a diagnostic tool we present evidence from the neurophysiology literature indicating that Alzheimer's disease and narcolepsy have some of the same brainstem nuclei implicated. Further, Alzheimer patients and narcoleptics share some of the same disturbed sleep patterns.

Adult↗

Neurological pupillary noise in narcolepsy.

Pupillometry has a long but inconclusive history as a means of measuring human alertness. Spontaneous pupillary oscillations in narcoleptics and the sleep deprived are a recognized but quantitatively elusive indication of alertness. Stimulation of the pupillary light reflex (PLR) has provided contradictory or confusion indications of alertness levels. Results from 10 diagnosed narcoleptics and 10 control subjects in which the PLR system was stimulated and a reliable (90%) discriminator derived for classifying narcoleptics and controls was reported. Random pupillary oscillations, which is called pupillary noise to distinguish these oscillations from spontaneous ones, were estimated from continuous pupil diameter recordings using a recursive least squares method applied to a subject-specific PLR system model. Pupillary noise sum of squares indicate that narcoleptics have significantly (P < 0.005) less PLR noise than controls. This difference was attributed to supranuclear inhibition of randomly active Edinger-Westphal neurons long hypothesized to be the source of random pupillary oscillations. This inhibition also has been suggested as a cause of PLR sensitivity to nocturnal sleep quality so it may be that these findings apply to the sleep deprived and not just specifically to narcoleptics.

Adult↗

Microwave effects on input resistance and action potential firing of snail neurons.

Excitable tissues have been reported to respond to weak microwave (MW) fields, possibly by nonlinear perturbation of a cellular process such as ion conduction across membranes. We sought effects of MW (continuous wave, 2.45 GHz, specific absorption rates 12.5 or 125 mW/g) on input resistances and action potential (AP) intervals of neurons in ganglia of snails (Helix aspersa), at 20.9 +/- 0.1 degrees C. At 12.5 mW/g, input resistance did not change during irradiation, but increased (p < 0.05) afterward. At 125 mW/g, input resistance during irradiation was lower than in unirradiated controls. Serial correlograms changed marginally more frequently in MW experiments than in controls, but the changes had no consistent pattern. The AP firing rate was affected by MW, but the direction was not consistent across cells. When AP generation was modeled as being due to a neuronal input current, MW did not affect its mean, standard deviation, or autocorrelation. Unlike MW, temperature changes caused neurons to respond robustly and reversibly. Threshold for changing input resistance was 0.63 degree C. The data suggest that MW may enhance degenerative effects such as metabolic rundown or loss of ion channel patency, but do not indicate a specific mechanism for MW interaction with neurons.

Action Potentials↗

Time series modeling of neuromuscular system.

The dynamic response of the human ankle joint to a bandlimited random torque perturbation superimposed on a constant bias torque is observed in normal human subjects. The applied torque input, the joint angular rotation output, and the electromyographic activity using surface electrodes from the extensor and the flexor muscles of the ankle joint were recorded. Transfer function models using time series techniques were developed for the torque - angular rotation input-output pair and for the angular rotation - electromyographic activity input-output pair. A parameter constraining technique was applied to develop more reliable models. It is shown that the asymptotic behavior of the system must be taken into account during parameter optimization to develop better predictive models.

Ankle Joint↗