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Biomedical subjects

R M Harper

Publications and source records attributed to R M Harper.

At least 127 records · Page 7Linked to original sources
PubMed1988

Methods of single unit recording from medullary neural substrates in awake, behaving guinea pigs.

An electrophysiological procedure that permits extracellular single neuronal recording in the medulla of unanesthetized, freely behaving animals is described. System components consist of 1) a flexible, single-strand microwire as recording electrode; 2) a miniature, skull-mounted miniature microdrive used for isolation of single unit activity; and 3) a head-mounted voltage follower that conditions and stabilizes the neuronal signals prior to amplification and transmission for further processing. A unique advantage of this procedure is the latitude and provision for microwire replacement in the event that multiple penetrations are desired or the tip of the microwire recording electrode is insulated as a result of gliomatosis. With minor modification, this technique can be used for single unit recording virtually anywhere along the supra-segmental neuraxis. Technical aspects of this procedure, together with details of design and fabrication of implantable devices, chronic instrumentation procedure, and potentials for other chronic applications, are discussed.

Action Potentials↗
PubMed1988

Cardiac and respiratory patterns in normal infants and victims of the sudden infant death syndrome.

Victims of the sudden infant death syndrome (SIDS) have higher overall heart rates prior to death than do control infants (1). The objective of this study was to partition these heart rate differences by state and to identify any state-dependent differences in heart rate variability and respiratory rate and variability. Twenty-two recordings of electrocardiogram (ECG) and respiration from 16 infants who subsequently died of SIDS were compared with 66 recordings of age-matched control infants. Median cardiac and respiratory rate and variability were computed for each sleep state in each recording, and one-way analysis of variance tests were performed for each variable for infants less than 1 month and for infants greater than 1 month of age. Heart rate was higher in SIDS victims less than 1 month of age than in age-matched controls during all sleep-waking states. SIDS victims greater than 1 month showed higher heart rates during rapid eye movement sleep only. Heart rate variability was also diminished during waking in victims less than 1 month, but much of this difference could be attributed to increased heart rate. These results suggest that, as a group, SIDS victims differ physiologically from control infants and that these differences may be especially prominent during particular sleep-waking states.

Electrocardiography↗
PubMed1988

Spectral analysis assessment of respiratory sinus arrhythmia in normal infants and infants who subsequently died of sudden infant death syndrome.

Reduced heart rate variability has been found in infants who later succumb to the sudden infant death syndrome (SIDS). To determine whether respiratory sinus arrhythmia, a major component of heart rate variability, is also reduced in SIDS victims, nighttime portions of eighteen 24-h recordings of ECG and respiration from infants who later died of SIDS and 52 recordings from control infants were assessed using spectral analysis. Two aspects of respiratory sinus arrhythmia were examined: "extent" (the absolute heart rate variation at the respiratory frequency) and "coherence" (the degree to which heart rate follows respiration regardless of the absolute amount of variation). Respiratory parameters were used to classify each 1-min epoch as quiet sleep, rapid eye movement sleep, waking, or indeterminate state. Median extent and coherence values across the night were then computed for each sleep-waking state. Two-way (group X state) repeated measures analysis of variance tests were then used to compare respiratory sinus arrhythmia values for 13 SIDS victims and 13 control infants matched by postnatal age, birth weight, sex, and gestational age. Extent of respiratory sinus arrhythmia was significantly lower in the SIDS victims across all sleep-waking states, a finding that persisted after adjusting for heart rate. Coherence values did not differ significantly. These results suggest that even before the time of maximal risk for the syndrome, SIDS victims, as a group, differ from controls in the extent to which cardiac and respiratory activity couple, and this difference is independent of basal heart rate.

Algorithms↗
PubMed1988

Cardiovascular and respiratory relationships with neuronal discharge in the central nucleus of the amygdala during sleep-waking states.

We examined state-related relationships of neuronal discharge in the central nucleus of the amygdala (ACE) with cardiac and respiratory patterning. ACE cell discharges correlated with cardiac and respiratory timing, arterial pressure, and several respiratory parameters in undrugged, freely moving cats during waking, quiet sleep, and rapid eye movement sleep. Phasic discharge with the cardiac or respiratory cycle was examined using cross-correlation histograms. Of 80 cells in 8 cats, 24% showed a timing relationship with the cardiac or respiratory cycle, i.e., a tendency to discharge with each cardiac R-wave or with each breath, 12% with the cardiac cycle, and 14% with the respiratory cycle (2 cells showed both). All timing relationships were state dependent, usually observed in only one sleep-waking state per cell. Over half the cells showed a significant Pearson's r rate correlation with respiratory period or arterial pressure. Two-thirds of the cells showing arterial pressure correlations also correlated with respiratory period. A substantial proportion of ACE cells thus shows a state-dependent modulation of discharge rate and pattern by cardiovascular and respiratory variables. Rate and timing relationships were mutually exclusive within states, suggesting a state-dependent functional differentiation within the ACE.

Amygdala↗
PubMed1987

Machine classification of infant sleep state using cardiorespiratory measures.

We examined the potential to classify sleep and waking state over the first 6 months of life in normal infants using only cardiac and respiratory measures. Twelve hour all-night polygraph recordings which included EEG, eye movement, whole body movement, facial muscle electromyographic, cardiac, and respiratory activity from 25 normal infants were collected at 1 week, and at 1, 2, 3, 4, and 6 months of age. Each minute of these recordings was classified into quiet sleep, waking, or rapid eye movement sleep by trained observers using EEG and somatic criteria. Respiratory rate and variability, heart rate and variability, and cardiac interbeat interval variation at respiratory and lower frequencies from 12 of the 25 infants were used as measures in discriminant analyses of sleep state for test on the 13 remaining infants. Using all 7 cardiac and respiratory measures, sleep states were classified with an accuracy approximating that attained by trained observers who had available all polygraph tracings (84.8% overall correct classification). Using only cardiac measures, the accuracy of classification decreased slightly, with an overall correct classification of 82.0%. Using only respiratory measures, the accuracy of classification diminished further, with an overall correct classification of 80.0%. Cardiac and respiratory measures provide quantifiable indications of sleep and waking states over the first 6 months of life in normal infants.

Computers↗
PubMed1987

State-dependent respiratory depression elicited by stimulation of the orbital frontal cortex.

The effect of electrical stimulation of the orbital frontal cortex on respiration was studied in unanesthetized, freely moving cats across sleep-waking states. Single trains of forty 300-microA, 0.5-ms, constant-current pulses at 60 Hz were delivered to the orbital frontal cortex at four points in the respiratory cycle. Stimuli delivered during expiration produced an immediate switch to inspiration. Stimuli delivered during inspiration reduced inspiratory EMG slope and peak EMG amplitude, and prolonged inspiration. Stimuli delivered during early inspiration produced greater effects than stimuli delivered during late inspiration. Stimulation effects were elicited during quiet waking and quiet sleep but not during rapid-eye-movement sleep. These results suggest that the orbital frontal cortex may contribute to respiratory phase switching, and that its influence on brain stem structures is attenuated during rapid-eye-movement sleep.

Animals↗
PubMed1987

Differential inhibition of the diaphragm and posterior cricoarytenoid muscles induced by transient hypertension across sleep states in intact cats.

Arterial pressure was transiently elevated by intravenous infusion of phenylephrine in intact, freely moving cats during sleep and waking states to determine pressure effects on diaphragmatic and laryngeal abductor EMG activity. Transient hypertension caused respiratory cycle duration to increase and integrated EMG area to decrease for several breaths in both the diaphragm and posterior cricoarytenoid, the integrated inspiratory area of which decreased to a greater extent than did that of the diaphragm. Cycle duration increases resulted from increases in expiratory duration. Expiratory duration of the posterior cricoarytenoid initially increased proportionately more than that of the diaphragm, causing a transient phase disassociation between that upper airway muscle and diaphragmatic timing. This disassociation disappeared after several breaths. Changes in posterior cricoarytenoid expiratory duration and integrated inspiratory area were sleep state-dependent: area decreases were greatest in rapid eye movement sleep; expiratory duration increases were greatest in quiet sleep. Neural mechanisms underlying laryngeal abductor activity are sleep state-dependent and appear to be affected more than diaphragmatic mechanisms by baroreceptor stimulation.

Animals↗
PubMed1986

Cryogenic blockade of the central nucleus of the amygdala attenuates aversively conditioned blood pressure and respiratory responses.

The central nucleus of the amygdala (ACE) was reversibly blocked during extinction of an aversively conditioned cardiorespiratory response in unanesthetized, freely moving cats. Cryoprobes were positioned bilaterally in the ACE of 4 cats and in the nucleus entopeduncularis of 1 cat. Blood pressure typically showed biphasic changes in response to the conditioned stimulus (CS) during non-cooling trials. Blood pressure initially dropped and then rose. Heart rate consistently dropped, and respiratory rate increased in response to the CS. ACE cooling did not alter the pre-CS baseline blood pressure, heart rate or respiratory timing, but changed the cardiorespiratory response to the CS. During ACE cooling, blood pressure and respiratory responses were greatly attenuated or abolished. No significant effect on the heart rate response was observed during ACE cooling. Cooling of a nearby structure, the nucleus entopeduncularis, did not affect blood pressure, heart rate or respiratory responses to the CS. These results support the hypothesis that the ACE plays a role in both cardiovascular and respiratory regulation during conditioned aversive responses. The study also suggests that, in cats, the predominant influence of the ACE on cardiovascular control is on blood pressure rather than on heart rate regulation.

Amygdala↗
PubMed1986

Respiratory modulation of neuronal discharge in the central nucleus of the amygdala during sleep and waking states.

The relationship between neuronal discharge in the central nucleus of the amygdala (ACE) and timing of the respiratory cycle was assessed during quiet and active sleep and during the waking state. Of 169 neurons recorded from the ACE in intact, drug-free cats, 22% discharged phasically with the respiratory cycle during at least one sleep or waking state. The dependency between neuronal discharge and the respiratory cycle was typically strong in only one state. Forty-three percent of the respiratory-related neurons were most strongly correlated with the respiratory cycle during the waking state (AW). An additional 30% were most strongly related to the respiratory cycle during quiet sleep (QS), whereas only 11% showed the strongest dependency during rapid eye movement (REM) sleep. Half of the ACE neurons (49%) discharged at frequencies less than 10 spikes per second, and the most common trend in firing rate across states was one in which neurons fired more rapidly during AW and REM than during QS. No relationship between discharge rate of ACE neurons in the three states and propensity for phasic discharge with the respiratory cycle could be demonstrated.

Amygdala↗
PubMed1986

Cardiac and respiratory relationships with neural discharge in the anterior cingulate cortex during sleep-walking states.

The discharge properties of single neurons in the anterior cingulate cortex were correlated with timing aspects of the respiratory and cardiac cycle and with arterial pressure in undrugged, freely moving cats during waking, quiet sleep, and rapid eye movement sleep (REM). Two types of analyses were carried out. Discharge timing relationships with the cardiac or respiratory cycle were examined using cross-correlation histograms. Tonic rate correlations were calculated as a linear regression between breath-by-breath mean discharge rate of the cell and breath-by-breath values of respiratory parameters or arterial pressure. Eight of fifty-five cells recorded showed a discharge timing relationship with either the cardiac or the respiratory cycle. Seven of these were state-dependent (six in waking, one in REM). Thirty cells showed a tonic rate correlation with the respiratory period, and 23 cells had tonic correlations with maximum arterial pressure. All tonic correlations for a given cell were state-dependent, but such correlations were observed in all states. Correlation coefficients, while statistically significant, were generally low, and r2 values rarely exceeded 0.2. The relative paucity of discharge timing relationships, the state dependency, and the low r values of the tonic rate correlations suggest that the anterior cingulate cortex has a complex and indirect relationship to central cardiovascular and respiratory control mechanisms.

Animals↗
PubMed1986

A miniaturized cryoprobe for functional neuronal blockade in freely moving animals.

We have developed a miniature cryoprobe for blockade of neuronal structures. The cryoprobe uses Freon as a cooling medium and consists of concentric double stainless steel cannulae, a shaft heater coil and a tip thermocouple. The cryoprobe tip temperature is controlled by adjusting Freon flow supplying the cryoprobe by an automobile fuel injector and electronic control circuit, and is displayed on a temperature monitor. Tissue temperatures, determined by thermocouples, ranged from 8.5 degrees C near the cryoprobe tip to 20 degrees C 2.5 mm distal to the tip. The cryoprobe shaft is maintained at body temperature by means of a shaft heater coil and a heater control circuit. The cryoprobe offers advantages of ease of construction, and allows cooling of neuronal structures in freely moving animal preparations.

Animals↗
PubMed1986

State-related physiological changes and risk for the sudden infant death syndrome.

Sleep-states alter the influences exerted by suprapontine structures on respiratory and cardiac patterning. These influences consist of normal modulation exerted by descending cortical and limbic structures, and include hypothalamic temperature control. Rapid eye movement sleep dissociates hypothalamic activity from temperature control and nearly abolishes blood pressure rises and respiratory pattern changes induced by stimulation of suprapontine regions. Sleep-states also regulate the occurrence of aberrant cardiorespiratory influences from epileptiform activity manifested in suprapontine structures by altering the threshold for seizure incidence. Thus, sleep may pose particular states of vulnerability for the Sudden Infant Death Syndrome (SIDS), since both temperature influences on respiration and aberrant suprapontine epileptiform activity may be factors underlying the mechanism of failure in SIDS.

Body Temperature Regulation↗
PubMed1985

Respiratory inhibition induced by transient hypertension during sleep in unrestrained cats.

The effects of transient blood pressure elevation, induced by intravenous injection of phenylephrine, were studied in drug-free, unrestrained cats during sleep and waking. Transient hypertension evoked an increase in respiratory cycle duration (Ttot), an effect which was most prominent during quiet sleep. Transient hypertension evoked no overall change in inspiratory duration (Tdi) during any sleep-waking state, although reduction of diaphragmatic EMG amplitude was observed. Thus, the ratio of diaphragmatic activity time to total respiratory cycle duration (Tdi/Ttot) was decreased following blood pressure elevation. Apneic episodes occasionally occurred, and these occurrences were more frequent during sleep states. Apneas induced during quiet sleep were often associated with transient or sustained arousal.

Animals↗
PubMed1985

Sleep-waking modulation of respiratory sinus arrhythmia in aged and young adult cats.

Heart rate variation at the respiratory frequency was examined in young adult and aged cats during waking and quiet sleep. Respiratory sinus arrhythmia was found to be significantly enhanced during quiet sleep compared with waking in both groups of cats. Aged cats exhibited respiratory sinus arrhythmia comparable to that of young adult cats during both waking and quiet sleep.

Age Factors↗
PubMed1984

Information trains. The technique and its uses in spike train and network analysis, with examples taken from the nucleus parabrachialis medialis during sleep-waking states.

We describe an analytical procedure for assessing functional interactions between neuronal spike trains based on the outcome of cross-correlation procedures. Subsets of a reference cell spike train in a two-train recording are extracted, based on their time-locked relationship to spikes in the dependent train. Such timing relationships comprise the significant primary structures in the cross-correlogram. Different subsets can be extracted for different primary structures in the same correlogram (i.e. a subset responsible for an interaction effect, a subset responsible for a shared input effect, etc.). These new spike trains represent an information transfer process across synapses. These 'information trains' may be compared and correlated to different cells of the network across different functional conditions such as sleep-waking states, and may also be subjected to conventional spike train analysis techniques such as rate histogram, auto-correlation and cross-correlation procedures. We illustrate the information train procedures with a network analysis of a set of cells recorded in the nucleus parabrachialis medialis during different sleep-waking states.

Action Potentials↗
PubMed1984

State-dependent alteration of respiratory cycle timing by stimulation of the central nucleus of the amygdala.

The effect of electrical stimulation of the amygdaloid central nucleus (ACE) on respiration was studied in unanesthetized, unrestrained cats during sleep-waking states. Single 0.5-ms 500-microA constant-current pulses delivered to the ACE at various points on the respiratory cycle, produced a transient inspiratory effort which summated with ongoing inspiratory activity and reduced inspiratory time. Stimulus pulses delivered during the expiratory phase resulted in an earlier shift to inspiration. Repetitive single pulse stimuli delivered to the ACE at a rate slightly faster than the spontaneous respiratory cycle during the alert state, were capable of 'entraining' respiration at the stimulus frequency. This entrainment disappeared in quiet sleep. Atropine, however, which produced synchronous high voltage slow waves and 12-14-Hz EEG spindle activity in the alert cat, did not impair this entrainment. Short (300-500 ms) 100-Hz trains of 0.5-ms pulses to the ACE produced rapid onset, sustained inspiration and a rise in blood pressure in the alert animal. During quiet sleep the response was attenuated but qualitatively similar, and also aroused the animal. Single pulse stimuli, however, were not associated with cardiovascular changes or generalized arousal. These results suggest that the ACE contributes to excitation of the inspiratory cycle, possibly through the large projection of this nucleus to the parabrachial pons.

Amygdala↗