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Biomedical subjects

R M Harper

Publications and source records attributed to R M Harper.

At least 109 records · Page 6Linked to original sources

Dynamic characteristics of cardiac R-R intervals during sleep and waking states.

Traditional assessment of cardiac R-R intervals during sleep-wake states uses summary statistics such as mean and interquartile range. Such summary statistics are less able to provide information about instantaneous or dynamic aspects of beat-to-beat control. We examined state-dependent beat-to-beat patterning by plotting each cardiac R-R interval against the previous interval (Poincaré plots). This procedure provides an indication of the probability of occurrence of one interval from its predecessor and allows assessment of dynamic properties of R-R interval variation. Cardiac R-R intervals were determined over 5-12-minute periods of wakefulness (AW), quiet sleep (QS) and rapid eye movement sleep (REM) from six cats; each interval was plotted on the y-axis against the previous value on the x-axis resulting in an RRn + 1 vs. RRn plot. These plots provided evidence that the correlation between an interval and its successor was greater in REM than in QS, even though the overall range was greater in REM. The results suggest that short-term cardiac control during REM may be influenced by more closely regulated mechanisms than suggested by classic concepts.

Animals↗

Postnatal development of cardiac and respiratory control following prenatal drug exposure.

Of primary importance in the consideration of animal models of prenatal drug exposure is the recognition of interdependence among physiologic systems, the pervading influence of sleep and waking states, and the potential interaction between drug-induced structural changes and physiologic function. It is difficult for a drug effect on the cardiovascular system not to modify respiratory pattern; any change in blood pressure, systemic perfusion, or heart rate is immediately reflected in breathing; respiratory pattern, in turn, through negative thoracic pressure and other sensory activity, can alter cardiac patterning. The respiratory system itself is one component of a somatic motor system, and neural motor control structures undergo substantial modification by drug action. Enhancing or diminishing any aspect of interaction is the influence of sleep states, which nonlinearly can alter relationships between physiologic systems, occasionally dissociating systems, as in the case of temperature effects on breathing during REM sleep. Finally, drug-induced structural changes that alter morphology of the upper airway can result in obstructive respiratory events, leading to pronounced cardiovascular sequelae.

Child, Preschool↗

Time of night effects on heart rate variation in normal neonates.

Circadian patterns have been observed in infants as early as the first few postnatal days. We hypothesized that, in each sleep-waking state, heart rate variation in several distinct frequency bands would show consistent variations across a night in newborn infants. Twelve-hour night-time recordings of EEG, ECG, EOG, digastric EMG, respiratory movements, and CO2 were obtained from 25 normal full-term infants at 2-7 days postnatal age. The extents of three types of heart rate variation were determined for all epochs identified as quiet sleep, rapid eye movement (REM) sleep, and waking during each 4-hr period of the night. In particular states, the extent of all three types of heart rate variation decreased from the evening (7-11pm) to the late night (11pm-3am). Heart rate variation at the respiratory frequency showed such a time-of-night effect in quiet sleep only, resulting in a significant sleep state effect on respiratory sinus arrhythmia during the evening that disappeared later in the night. Previous studies have indicated that respiratory sinus arrhythmia is enhanced during quiet sleep, relative to other states, after 3 mo of age; the present findings suggest that the tendency for enhancement during quiet sleep is present even in the neonate, although this tendency is only expressed during the evening. Results indicate that time-of-night effects on heart rate variation are not constant across physiological states in neonates, and heart rate variation during the waking state is particularly unresponsive to these time-of-night influences.

Analysis of Variance↗

Sleep apnea in infants who succumb to the sudden infant death syndrome.

Previous studies have shown the frequency of respiratory pauses to be altered in groups of infants at risk for the sudden infant death syndrome (SIDS). In this study, we assess the frequency of apneic pauses during quiet sleep and rapid eye movement sleep in control infants and infants who subsequently died of SIDS. Sleep states were identified in 12-hour physiological recordings of SIDS victims and matched control infants, and the number of respiratory pauses from 4 to 30 seconds in duration was computed for quiet sleep and rapid eye movement sleep. SIDS victims 40 to 65 days of age showed significantly fewer apneic pauses than did age-matched control infants across the two sleep states. Fewer short respiratory pauses accounted for most of the reduction in number of apneic events in the SIDS victims during both sleep states. During the first month of life, SIDS victims did not differ significantly from control neonates on this measure. The finding that this respiratory difference exists during the second month of life, just before the period of maximal risk for SIDS, but not earlier, may have implications for the etiology of SIDS deaths.

Electrocardiography↗

Cardiovascular-related discharge of periaqueductal gray neurons during sleep-waking states.

The periaqueductal gray (PAG) contains topographically organized areas that, upon stimulation or lesion, lead to modifications in blood pressure and heart rate and redistribution of blood flow. We examined patterns of discharge of single neurons in the PAG in 5 undrugged, freely moving cats to determine if cardiovascular patterning changes observed during different sleep states were related to activity in this midbrain region. Cross-correlation histograms and linear regression techniques were used to calculate dependencies between neuronal discharge and cardiac activity. Fifty of 68 cells recorded (74%) showed a discharge timing relationship (cardiac cycle-by-cycle) and/or a tonic discharge correlation with the cardiac cycle. Nearly all (48 or 96%) of these dependencies were state related. The large proportion of neurons showing a state-related cardiac dependency suggests that the PAG may contribute to mediating different cardiac patterns observed in each state.

Animals↗

Respiratory-related discharge of periaqueductal gray neurons during sleep-waking states.

Extracellular single-unit spontaneous activity was recorded from the periaqueductal gray region (PAG) in undrugged, freely moving cats. Two analyses, cross-correlation histograms and linear regression techniques, were used to examine state relationships of neuronal discharge with respiratory patterning. Of 68 cells recorded, 19 (28%) showed a timing relationship (breath-by-breath dependency), 14 of which were state-dependent. Twenty-three (34%) showed a tonic discharge correlation with the respiratory cycle, and activity of all these cells was state-dependent. These results suggest that a subset of PAG cells may play a role in state-related respiratory patterning.

Action Potentials↗

Recurring discharge patterns in multiple spike trains. I. Detection.

We present a procedure to detect recurring discharge patterns in multiple spike trains. Such recurring patterns can include many spikes and involve from three to many spike trains. The pattern detection procedure is based on calculating the exact probability of randomly obtaining each individually recurring pattern. The statistical evaluation is based on the use of 2 x 2 contingency tables and the application of Fisher's exact test. Several simulations are applied to evaluate the method. Findings based on applying the procedure to simultaneously recorded spike and event trains are described in a companion paper (Frostig et al. 1990).

Action Potentials↗

Recurring discharge patterns in multiple spike trains. II. Application in forebrain areas related to cardiac and respiratory control during different sleep-waking states.

Simultaneously recorded spike trains were obtained using microwire bundles from unrestrained, drug-free cats during different sleep-waking states in forebrain areas associated with cardiac and respiratory activity. Cardiac and respiratory activity was simultaneously recorded with the spike trains. We applied the recurring discharge patterns detection procedure described in a companion paper (Frostig et al. 1990) to the spike and cardiorespiratory trains. The pattern detection procedure was applied to detect only precise (in time and structure) recurring patterns. Recurring discharge patterns were detected in all simultaneously recorded groups. Recurring discharge patterns were composed of up to ten spikes per pattern and involved up to four simultaneously recorded spike trains. Fourty-two percent of the recurring patterns contained cardiac and/or respiratory events in addition to neuronal spikes. When patterns were compared over different sleep-waking states it was found the the same units produced different patterns in different states, that patterns were significantly more compact in time during quiet sleep, and that changes in the discharge rates accompanying changes in sleep-waking states were not correlated with changes in pattern rate.

Action Potentials↗

Correlations between cardiorespiratory measures in normal infants and victims of sudden infant death syndrome.

Coordination between physiological measures (i.e., the tendency for measures to co-vary with each other) develops with maturation in the infant. We hypothesized that correlations between cardiorespiratory measures would increase with maturation in normal infants and that infants destined to die of sudden infant death syndrome (SIDS) would show lower correlations than those of age-matched controls. Twenty-two recordings of electrocardiogram and respiratory movements were obtained from infants who subsequently succumbed to SIDS and compared with 66 recordings from control infants. Each 1-min epoch of data was sleep-state classified. Median heart and respiratory rate, respiratory variability, and median extent of three types of heart rate variation were determined for each epoch, and the minute-by-minute correlations between seven pairs of parameters were determined for quiet sleep, rapid eye movement sleep, and waking in each recording. Most cardiorespiratory measures showed correlations that increased with age; the correlation coefficients for these measures tended to be lower in SIDS victims than in controls prior to 2 weeks of age. The correlations between heart rate and heart rate variability became lower with maturation; correlations between these measures tended to be higher in the SIDS victims. In all analyses showing significant maturational trends, the SIDS victims showed "less mature" correlations than those of the controls.

Arrhythmias, Cardiac↗

Multimodality imaging of brain structures for stereotactic surgery.

An image analysis system was developed for stereotactic neurosurgery that allows the simultaneous display of brain images from different imaging devices obtained in different orientations. The system is based on a stereotactic frame and a microcomputer and features an easy user interface together with point registration and region of interest analysis in three-dimensional space. A dynamic multi-image environment allows for simultaneous display of magnetic resonance, computed tomography, digital subtraction angiography, and positron emission tomography images in multiple windows, adjusted for common coordinates with reference to stereotactic frame fiducial markers. Linkages between images allow information interchange between different modalities and different views: Points and regions defined in one image can be transferred to others, and cursor coordinates in one image can be calculated and dynamically projected in other images. Phantom studies show that the system distortions are minor and that the system is suitable for clinical use. The system provides exceptional advantages over previous imaging procedures for stereotactic surgery.

Angiography, Digital Subtraction↗

Stereotactic investigation of limbic epilepsy using a multimodal image analysis system. Technical note.

A methodology has been developed for stereotactic investigation of limbic epilepsy using an image-analysis system that simultaneously displays different structural and functional images of the brain. The validity and accuracy of this system were established with phantom studies. Surgical planning and electrode implantation are guided by stereotactic magnetic resonance imaging, digital subtraction angiography, and position emission tomography. This methodology provides the spatiotemporal relationship of cerebral structure and function necessary to identify seizure onset and propagation in human limbic system epilepsy.

Brain Mapping↗

Cardiac and respiratory correlations with unit discharge in human amygdala and hippocampus.

Animal studies have shown that epileptiform seizures can cause cardiac arrhythmias and death. The amygdala and hippocampus are implicated in epileptogenesis and autonomic and respiratory control. We examined cardiac and respiratory correlations with single cell discharge in hippocampus and amygdala of patients with epilepsy. We recorded respiration, ECG, and neuronal discharge of amygdala and hippocampus from patients undergoing chronic depth electrode monitoring. Cross-correlation histograms were used to test for neuronal discharge timing relationships with inspiration or the ECG. Inspiratory time, respiratory period and heart rate were calculated for each breath, and linear regression was used to test for correlations with tonic unit rate. Of 183 cells from 24 patients, 20% had cardiac timing relationships and 23% showed tonic correlations with changes in heart rate. Only 2% had timing relationships with the respiratory cycle, while 15% showed tonic rate relationships with respiratory period. Recording sites did not differ in mean discharge rate or proportion of cells showing these correlations. These results indicate that a significant number of human forebrain cells show discharge modulation by the cardiac cycle and discharge rate correlation with changes in respiration and heart rate. This is supportive of animal models designed to explore the role of mesial temporal lobe structures in regulation of cardiovascular and respiratory systems, although a lower proportion of cells in human temporal lobe showed timing relationships with respiration and there was no clear evidence of anatomic specificity between amygdala and hippocampus.

Amygdala↗

A procedure for chronic recording of diaphragmatic electromyographic activity.

A simple procedure for recording of diaphragmatic electromyographic activity in awake, freely behaving animals is described. This procedure produces highly stable recording of muscle activity for very long periods. Because of its ease of use, the procedure has become the technique of choice for acute recording in our laboratories as well. The present procedure can also be adapted for chronic recording of electromyographic activities from nonrespiratory muscles. This option thus offers a variety of applications to those involved in investigations into the central neuromotor control of movement, pattern generation and autonomic functions.

Animals↗

Heart rate variation in normal infants and victims of the sudden infant death syndrome.

Infants who later succumb to the sudden infant death syndrome (SIDS) exhibit lower overall heart rate variability during waking than do other infants. This study attempts to determine which type or types of heart rate variation are reduced in SIDS victims. Long-term recordings of heart rate and respiration were obtained from normal infants and infants who later died of SIDS, and heart rate variation in three frequency bands was examined: respiratory sinus arrhythmia (periods 0.9-3.0 s), 'mid-frequency' (periods 4.0-7.5 s) and 'low-frequency' (periods 12-30 s). All three types of heart rate variation were diminished in SIDS victims under 1 month of age during waking and rapid eye movement (REM) sleep compared with controls. Partitioning heart rate effects showed that in waking, and to a lesser extent in REM sleep, the reduction in all types of heart rate variation exceeded that which would have been predicted based on higher heart rates in SIDS victims. No heart rate-independent reduction in any type of heart rate variation was observed in quiet sleep. This state-dependent reduction in three types of heart rate variation could indicate an abnormality of autonomic control mechanisms during waking and REM sleep in infants who later succumb to SIDS.

Age Factors↗

Development of heart rate variation over the first 6 months of life in normal infants.

Development of heart rate variation in three frequency ranges was examined during sleep-walking states in normal infants over the first 6 mo of life. Extent of all three types of heart rate variation decreased from 1 wk to 1 mo of age. Extent of respiratory sinus arrhythmia increased from 1 mo to 6 mo during all sleep-waking states, with the increase most pronounced during quiet sleep. Variation in two bands of lower frequencies showed increases in extent from 1 to 3 mo, then a slowing or reversal of the increase between 3 and 4 mo of age. During rapid eye movement sleep, the two types of lower frequency heart rate variation decreased in extent from 3 through 6 mo of age. These results suggest that alterations in autonomic control of heart rate occur at several time periods over the first 6 mo of life and that these alterations may have an effect only on particular types of heart rate variation and only during particular sleep-waking states. The diminution of all three types of heart rate variation at 1 mo may indicate a reduction in vagal tone at this age.

Aging↗